METHODS AND COMPOSITIONS FOR DIAGNOSIS AND PROGNOSIS OF RENAL INJURY AND RENAL FAILURE

Information

  • Patent Application
  • 20150038595
  • Publication Number
    20150038595
  • Date Filed
    July 05, 2012
    11 years ago
  • Date Published
    February 05, 2015
    9 years ago
Abstract
The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator as diagnostic and prognostic biomarkers in renal injuries.
Description
BACKGROUND OF THE INVENTION

The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.


The kidney is responsible for water and solute excretion from the body. Its functions include maintenance of acid-base balance, regulation of electrolyte concentrations, control of blood volume, and regulation of blood pressure. As such, loss of kidney function through injury and/or disease results in substantial morbidity and mortality. A detailed discussion of renal injuries is provided in Harrison's Principles of Internal Medicine, 17th Ed., McGraw Hill, N.Y., pages 1741-1830, which are hereby incorporated by reference in their entirety. Renal disease and/or injury may be acute or chronic. Acute and chronic kidney disease are described as follows (from Current Medical Diagnosis & Treatment 2008, 47th Ed, McGraw Hill, N.Y., pages 785-815, which are hereby incorporated by reference in their entirety): “Acute renal failure is worsening of renal function over hours to days, resulting in the retention of nitrogenous wastes (such as urea nitrogen) and creatinine in the blood. Retention of these substances is called azotemia. Chronic renal failure (chronic kidney disease) results from an abnormal loss of renal function over months to years”.


Acute renal failure (ARF, also known as acute kidney injury, or AKI) is an abrupt (typically detected within about 48 hours to 1 week) reduction in glomerular filtration. This loss of filtration capacity results in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products that are normally excreted by the kidney, a reduction in urine output, or both. It is reported that ARF complicates about 5% of hospital admissions, 4-15% of cardiopulmonary bypass surgeries, and up to 30% of intensive care admissions. ARF may be categorized as prerenal, intrinsic renal, or postrenal in causation. Intrinsic renal disease can be further divided into glomerular, tubular, interstitial, and vascular abnormalities. Major causes of ARF are described in the following table, which is adapted from the Merck Manual, 17th ed., Chapter 222, and which is hereby incorporated by reference in their entirety:













Type
Risk Factors







Prerenal



ECF volume depletion
Excessive diuresis, hemorrhage, GI losses, loss of



intravascular fluid into the extravascular space (due to



ascites, peritonitis, pancreatitis, or bums), loss of skin



and mucus membranes, renal salt- and water-wasting



states


Low cardiac output
Cardiomyopathy, MI, cardiac tamponade, pulmonary



embolism, pulmonary hypertension, positive-pressure



mechanical ventilation


Low systemic vascular
Septic shock, liver failure, antihypertensive drugs


resistance


Increased renal vascular
NSAIDs, cyclosporines, tacrolimus, hypercalcemia,


resistance
anaphylaxis, anesthetics, renal artery obstruction, renal



vein thrombosis, sepsis, hepatorenal syndrome


Decreased efferent
ACE inhibitors or angiotensin II receptor blockers


arteriolar tone (leading to


decreased GFR from


reduced glomerular


transcapillary pressure,


especially in patients with 


bilateral renal artery


stenosis)


Intrinsic Renal


Acute tubular injury
Ischemia (prolonged or severe prerenal state): surgery,



hemorrhage, arterial or venous obstruction; Toxins:



NSAIDs, cyclosporines, tacrolimus, aminoglycosides,



foscarnet, ethylene glycol, hemoglobin, myoglobin,



ifosfamide, heavy metals, methotrexate, radiopaque



contrast agents, streptozotocin


Acute glomerulonephritis
ANCA-associated: Crescentic glomerulonephritis,



polyarteritis nodosa, Wegener's granulomatosis; Anti-



GBM glomerulonephritis: Goodpasture's syndrome;



Immune-complex: Lupus glomerulonephritis,



postinfectious glomerulonephritis, cryoglobulinemic



glomerulonephritis


Acute tubulointerstitial
Drug reaction (eg, β-lactams, NSAIDs, sulfonamides,


nephritis
ciprofloxacin, thiazide diuretics, furosemide, phenytoin,



allopurinol, pyelonephritis, papillary necrosis


Acute vascular
Vasculitis, malignant hypertension, thrombotic


nephropathy
microangiopathies, scleroderma, atheroembolism


Infiltrative diseases
Lymphoma, sarcoidosis, leukemia


Postrenal


Tubular precipitation
Uric acid (tumor lysis), sulfonamides, triamterene,



acyclovir, indinavir, methotrexate, ethylene glycol



ingestion, myeloma protein, myoglobin


Ureteral obstruction
Intrinsic: Calculi, clots, sloughed renal tissue, fungus



ball, edema, malignancy, congenital defects; Extrinsic:



Malignancy, retroperitoneal fibrosis, ureteral trauma



during surgery or high impact injury


Bladder obstruction
Mechanical: Benign prostatic hyperplasia, prostate



cancer, bladder cancer, urethral strictures, phimosis,



paraphimosis, urethral valves, obstructed indwelling



urinary catheter; Neurogenic: Anticholinergic drugs,



upper or lower motor neuron lesion









In the case of ischemic ARF, the course of the disease may be divided into four phases. During an initiation phase, which lasts hours to days, reduced perfusion of the kidney is evolving into injury. Glomerular ultrafiltration reduces, the flow of filtrate is reduced due to debris within the tubules, and back leakage of filtrate through injured epithelium occurs. Renal injury can be mediated during this phase by reperfusion of the kidney. Initiation is followed by an extension phase which is characterized by continued ischemic injury and inflammation and may involve endothelial damage and vascular congestion. During the maintenance phase, lasting from 1 to 2 weeks, renal cell injury occurs, and glomerular filtration and urine output reaches a minimum. A recovery phase can follow in which the renal epithelium is repaired and GFR gradually recovers. Despite this, the survival rate of subjects with ARF may be as low as about 60%.


Acute kidney injury caused by radiocontrast agents (also called contrast media) and other nephrotoxins such as cyclosporine, antibiotics including aminoglycosides and anticancer drugs such as cisplatin manifests over a period of days to about a week. Contrast induced nephropathy (CIN, which is AKI caused by radiocontrast agents) is thought to be caused by intrarenal vasoconstriction (leading to ischemic injury) and from the generation of reactive oxygen species that are directly toxic to renal tubular epithelial cells. CIN classically presents as an acute (onset within 24-48 h) but reversible (peak 3-5 days, resolution within 1 week) rise in blood urea nitrogen and serum creatinine.


A commonly reported criteria for defining and detecting AKI is an abrupt (typically within about 2-7 days or within a period of hospitalization) elevation of serum creatinine. Although the use of serum creatinine elevation to define and detect AKI is well established, the magnitude of the serum creatinine elevation and the time over which it is measured to define AKI varies considerably among publications. Traditionally, relatively large increases in serum creatinine such as 100%, 200%, an increase of at least 100% to a value over 2 mg/dL and other definitions were used to define AKI. However, the recent trend has been towards using smaller serum creatinine rises to define AKI. The relationship between serum creatinine rise, AKI and the associated health risks are reviewed in Praught and Shlipak, Curr Opin Nephrol Hypertens 14:265-270, 2005 and Chertow et al, J Am Soc Nephrol 16: 3365-3370, 2005, which, with the references listed therein, are hereby incorporated by reference in their entirety. As described in these publications, acute worsening renal function (AKI) and increased risk of death and other detrimental outcomes are now known to be associated with very small increases in serum creatinine. These increases may be determined as a relative (percent) value or a nominal value. Relative increases in serum creatinine as small as 20% from the pre-injury value have been reported to indicate acutely worsening renal function (AKI) and increased health risk, but the more commonly reported value to define AKI and increased health risk is a relative increase of at least 25%. Nominal increases as small as 0.3 mg/dL, 0.2 mg/dL or even 0.1 mg/dL have been reported to indicate worsening renal function and increased risk of death. Various time periods for the serum creatinine to rise to these threshold values have been used to define AKI, for example, ranging from 2 days, 3 days, 7 days, or a variable period defined as the time the patient is in the hospital or intensive care unit. These studies indicate there is not a particular threshold serum creatinine rise (or time period for the rise) for worsening renal function or AKI, but rather a continuous increase in risk with increasing magnitude of serum creatinine rise.


One study (Lassnigg et all, J Am Soc Nephrol 15:1597-1605, 2004, hereby incorporated by reference in its entirety) investigated both increases and decreases in serum creatinine. Patients with a mild fall in serum creatinine of −0.1 to −0.3 mg/dL following heart surgery had the lowest mortality rate. Patients with a larger fall in serum creatinine (more than or equal to −0.4 mg/dL) or any increase in serum creatinine had a larger mortality rate. These findings caused the authors to conclude that even very subtle changes in renal function (as detected by small creatinine changes within 48 hours of surgery) seriously effect patient's outcomes. In an effort to reach consensus on a unified classification system for using serum creatinine to define AKI in clinical trials and in clinical practice, Bellomo et al., Crit. Care. 8(4):R204-12, 2004, which is hereby incorporated by reference in its entirety, proposes the following classifications for stratifying AKI patients:


“Risk”: serum creatinine increased 1.5 fold from baseline OR urine production of <0.5 ml/kg body weight/hr for 6 hours;


“Injury”: serum creatinine increased 2.0 fold from baseline OR urine production <0.5 ml/kg/hr for 12 h;


“Failure”: serum creatinine increased 3.0 fold from baseline OR creatinine >355 mmol/l (with a rise of >44) or urine output below 0.3 ml/kg/hr for 24 h or anuria for at least 12 hours;


And included two clinical outcomes:


“Loss”: persistent need for renal replacement therapy for more than four weeks.


“ESRD”: end stage renal disease—the need for dialysis for more than 3 months.


These criteria are called the RIFLE criteria, which provide a useful clinical tool to classify renal status. As discussed in Kellum, Crit. Care Med. 36: S141-45, 2008 and Ricci et al., Kidney Int. 73, 538-546, 2008, each hereby incorporated by reference in its entirety, the RIFLE criteria provide a uniform definition of AKI which has been validated in numerous studies.


More recently, Mehta et al., Crit. Care 11:R31 (doi:10.1186.cc5713), 2007, hereby incorporated by reference in its entirety, proposes the following similar classifications for stratifying AKI patients, which have been modified from RIFLE:


“Stage I”: increase in serum creatinine of more than or equal to 0.3 mg/dL (≧26.4 μmol/L) or increase to more than or equal to 150% (1.5-fold) from baseline OR urine output less than 0.5 mL/kg per hour for more than 6 hours;


“Stage II”: increase in serum creatinine to more than 200% (>2-fold) from baseline OR urine output less than 0.5 mL/kg per hour for more than 12 hours;


“Stage III”: increase in serum creatinine to more than 300% (>3-fold) from baseline OR serum creatinine ≧354 mmol/L accompanied by an acute increase of at least 44 mmol/L OR urine output less than 0.3 mL/kg per hour for 24 hours or anuria for 12 hours.


The CIN Consensus Working Panel (McCollough et al, Rev Cardiovasc Med. 2006; 7(4):177-197, hereby incorporated by reference in its entirety) uses a serum creatinine rise of 25% to define Contrast induced nephropathy (which is a type of AKI). Although various groups propose slightly different criteria for using serum creatinine to detect AKI, the consensus is that small changes in serum creatinine, such as 0.3 mg/dL or 25%, are sufficient to detect AKI (worsening renal function) and that the magnitude of the serum creatinine change is an indicator of the severity of the AKI and mortality risk.


Although serial measurement of serum creatinine over a period of days is an accepted method of detecting and diagnosing AKI and is considered one of the most important tools to evaluate AKI patients, serum creatinine is generally regarded to have several limitations in the diagnosis, assessment and monitoring of AKI patients. The time period for serum creatinine to rise to values (e.g., a 0.3 mg/dL or 25% rise) considered diagnostic for AKI can be 48 hours or longer depending on the definition used. Since cellular injury in AKI can occur over a period of hours, serum creatinine elevations detected at 48 hours or longer can be a late indicator of injury, and relying on serum creatinine can thus delay diagnosis of AKI. Furthermore, serum creatinine is not a good indicator of the exact kidney status and treatment needs during the most acute phases of AKI when kidney function is changing rapidly. Some patients with AKI will recover fully, some will need dialysis (either short term or long term) and some will have other detrimental outcomes including death, major adverse cardiac events and chronic kidney disease. Because serum creatinine is a marker of filtration rate, it does not differentiate between the causes of AKI (pre-renal, intrinsic renal, post-renal obstruction, atheroembolic, etc) or the category or location of injury in intrinsic renal disease (for example, tubular, glomerular or interstitial in origin). Urine output is similarly limited, Knowing these things can be of vital importance in managing and treating patients with AKI.


These limitations underscore the need for better methods to detect and assess AKI, particularly in the early and subclinical stages, but also in later stages when recovery and repair of the kidney can occur. Furthermore, there is a need to better identify patients who are at risk of having an AKI.


BRIEF SUMMARY OF THE INVENTION

It is an object of the invention to provide methods and compositions for evaluating renal function in a subject. As described herein, measurement of one or more biomarkers selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator (each referred to herein as a “kidney injury marker”) can be used for diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure (also called acute kidney injury).


The kidney injury markers of the present invention may be used, individually or in panels comprising a plurality of kidney injury markers, for risk stratification (that is, to identify subjects at risk for a future injury to renal function, for future progression to reduced renal function, for future progression to ARF, for future improvement in renal function, etc.); for diagnosis of existing disease (that is, to identify subjects who have suffered an injury to renal function, who have progressed to reduced renal function, who have progressed to ARF, etc.); for monitoring for deterioration or improvement of renal function; and for predicting a future medical outcome, such as improved or worsening renal function, a decreased or increased mortality risk, a decreased or increased risk that a subject will require renal replacement therapy (i.e., hemodialysis, peritoneal dialysis, hemofiltration, and/or renal transplantation, a decreased or increased risk that a subject will recover from an injury to renal function, a decreased or increased risk that a subject will recover from ARF, a decreased or increased risk that a subject will progress to end stage renal disease, a decreased or increased risk that a subject will progress to chronic renal failure, a decreased or increased risk that a subject will suffer rejection of a transplanted kidney, etc.


In a first aspect, the present invention relates to methods for evaluating renal status in a subject. These methods comprise performing an assay method that is configured to detect one or more biomarkers selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator is/are then correlated to the renal status of the subject. This correlation to renal status may include correlating the assay result(s) to one or more of risk stratification, diagnosis, prognosis, staging, classifying and monitoring of the subject as described herein. Thus, the present invention utilizes one or more kidney injury markers of the present invention for the evaluation of renal injury.


In certain embodiments, the methods for evaluating renal status described herein are methods for risk stratification of the subject; that is, assigning a likelihood of one or more future changes in renal status to the subject. In these embodiments, the assay result(s) is/are correlated to one or more such future changes. The following are preferred risk stratification embodiments.


In preferred risk stratification embodiments, these methods comprise determining a subject's risk for a future injury to renal function, and the assay result(s) is/are correlated to a likelihood of such a future injury to renal function. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of suffering a future injury to renal function is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of suffering a future injury to renal function is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold.


In other preferred risk stratification embodiments, these methods comprise determining a subject's risk for future reduced renal function, and the assay result(s) is/are correlated to a likelihood of such reduced renal function. For example, the measured concentrations may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of suffering a future reduced renal function is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of future reduced renal function is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold.


In still other preferred risk stratification embodiments, these methods comprise determining a subject's likelihood for a future improvement in renal function, and the assay result(s) is/are correlated to a likelihood of such a future improvement in renal function. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of a future improvement in renal function is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold. For a “negative going” kidney injury marker, an increased likelihood of a future improvement in renal function is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold.


In yet other preferred risk stratification embodiments, these methods comprise determining a subject's risk for progression to ARF, and the result(s) is/are correlated to a likelihood of such progression to ARF. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of progression to ARF is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of progression to ARF is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold.


And in other preferred risk stratification embodiments, these methods comprise determining a subject's outcome risk, and the assay result(s) is/are correlated to a likelihood of the occurrence of a clinical outcome related to a renal injury suffered by the subject. For example, the measured concentration(s) may each be compared to a threshold value. For a “positive going” kidney injury marker, an increased likelihood of one or more of: acute kidney injury, progression to a worsening stage of AKI, mortality, a requirement for renal replacement therapy, a requirement for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, progression to chronic kidney disease, etc., is assigned to the subject when the measured concentration is above the threshold, relative to a likelihood assigned when the measured concentration is below the threshold. For a “negative going” kidney injury marker, an increased likelihood of one or more of: acute kidney injury, progression to a worsening stage of AKI, mortality, a requirement for renal replacement therapy, a requirement for withdrawal of renal toxins, end stage renal disease, heart failure, stroke, myocardial infarction, progression to chronic kidney disease, etc., is assigned to the subject when the measured concentration is below the threshold, relative to a likelihood assigned when the measured concentration is above the threshold.


In such risk stratification embodiments, preferably the likelihood or risk assigned is that an event of interest is more or less likely to occur within 180 days of the time at which the body fluid sample is obtained from the subject. In particularly preferred embodiments, the likelihood or risk assigned relates to an event of interest occurring within a shorter time period such as 18 months, 120 days, 90 days, 60 days, 45 days, 30 days, 21 days, 14 days, 7 days, 5 days, 96 hours, 72 hours, 48 hours, 36 hours, 24 hours, 12 hours, or less. A risk at 0 hours of the time at which the body fluid sample is obtained from the subject is equivalent to diagnosis of a current condition.


In preferred risk stratification embodiments, the subject is selected for risk stratification based on the pre-existence in the subject of one or more known risk factors for prerenal, intrinsic renal, or postrenal ARF. For example, a subject undergoing or having undergone major vascular surgery, coronary artery bypass, or other cardiac surgery; a subject having pre-existing congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, glomerular filtration below the normal range, cirrhosis, serum creatinine above the normal range, or sepsis; or a subject exposed to NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin are all preferred subjects for monitoring risks according to the methods described herein. This list is not meant to be limiting. By “pre-existence” in this context is meant that the risk factor exists at the time the body fluid sample is obtained from the subject. In particularly preferred embodiments, a subject is chosen for risk stratification based on an existing diagnosis of injury to renal function, reduced renal function, or ARF.


In other embodiments, the methods for evaluating renal status described herein are methods for diagnosing a renal injury in the subject; that is, assessing whether or not a subject has suffered from an injury to renal function, reduced renal function, or ARF. In these embodiments, the assay result(s), for example measured concentration(s) of one or more biomarkers selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator is/are correlated to the occurrence or nonoccurrence of a change in renal status. The following are preferred diagnostic embodiments.


In preferred diagnostic embodiments, these methods comprise diagnosing the occurrence or nonoccurrence of an injury to renal function, and the assay result(s) is/are correlated to the occurrence or nonoccurrence of such an injury. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury to renal function is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury to renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury to renal function is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury to renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold).


In other preferred diagnostic embodiments, these methods comprise diagnosing the occurrence or nonoccurrence of reduced renal function, and the assay result(s) is/are correlated to the occurrence or nonoccurrence of an injury causing reduced renal function. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury causing reduced renal function is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury causing reduced renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury causing reduced renal function is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury causing reduced renal function may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold).


In yet other preferred diagnostic embodiments, these methods comprise diagnosing the occurrence or nonoccurrence of ARF, and the assay result(s) is/are correlated to the occurrence or nonoccurrence of an injury causing ARF. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of ARF is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of ARF may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of ARF is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of ARF may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold).


In still other preferred diagnostic embodiments, these methods comprise diagnosing a subject as being in need of renal replacement therapy, and the assay result(s) is/are correlated to a need for renal replacement therapy. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury creating a need for renal replacement therapy is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal replacement therapy may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury creating a need for renal replacement therapy is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal replacement therapy may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold).


In still other preferred diagnostic embodiments, these methods comprise diagnosing a subject as being in need of renal transplantation, and the assay result (s0 is/are correlated to a need for renal transplantation. For example, each of the measured concentration(s) may be compared to a threshold value. For a positive going marker, an increased likelihood of the occurrence of an injury creating a need for renal transplantation is assigned to the subject when the measured concentration is above the threshold (relative to the likelihood assigned when the measured concentration is below the threshold); alternatively, when the measured concentration is below the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal transplantation may be assigned to the subject (relative to the likelihood assigned when the measured concentration is above the threshold). For a negative going marker, an increased likelihood of the occurrence of an injury creating a need for renal transplantation is assigned to the subject when the measured concentration is below the threshold (relative to the likelihood assigned when the measured concentration is above the threshold); alternatively, when the measured concentration is above the threshold, an increased likelihood of the nonoccurrence of an injury creating a need for renal transplantation may be assigned to the subject (relative to the likelihood assigned when the measured concentration is below the threshold).


In still other embodiments, the methods for evaluating renal status described herein are methods for monitoring a renal injury in the subject; that is, assessing whether or not renal function is improving or worsening in a subject who has suffered from an injury to renal function, reduced renal function, or ARF. In these embodiments, the assay result(s), for example measured concentration(s) of one or more biomarkers selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator is/are correlated to the occurrence or nonoccurrence of a change in renal status. The following are preferred monitoring embodiments.


In preferred monitoring embodiments, these methods comprise monitoring renal status in a subject suffering from an injury to renal function, and the assay result(s) is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject.


In other preferred monitoring embodiments, these methods comprise monitoring renal status in a subject suffering from reduced renal function, and the assay result(s) is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject.


In yet other preferred monitoring embodiments, these methods comprise monitoring renal status in a subject suffering from acute renal failure, and the assay result(s) is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject.


In other additional preferred monitoring embodiments, these methods comprise monitoring renal status in a subject at risk of an injury to renal function due to the pre-existence of one or more known risk factors for prerenal, intrinsic renal, or postrenal ARF, and the assay result(s) is/are correlated to the occurrence or nonoccurrence of a change in renal status in the subject. For example, the measured concentration(s) may be compared to a threshold value. For a positive going marker, when the measured concentration is above the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is below the threshold, an improvement of renal function may be assigned to the subject. For a negative going marker, when the measured concentration is below the threshold, a worsening of renal function may be assigned to the subject; alternatively, when the measured concentration is above the threshold, an improvement of renal function may be assigned to the subject.


In still other embodiments, the methods for evaluating renal status described herein are methods for classifying a renal injury in the subject; that is, determining whether a renal injury in a subject is prerenal, intrinsic renal, or postrenal; and/or further subdividing these classes into subclasses such as acute tubular injury, acute glomerulonephritis acute tubulointerstitial nephritis, acute vascular nephropathy, or infiltrative disease; and/or assigning a likelihood that a subject will progress to a particular RIFLE stage. In these embodiments, the assay result(s), for example measured concentration(s) of one or more biomarkers selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator is/are correlated to a particular class and/or subclass. The following are preferred classification embodiments.


In preferred classification embodiments, these methods comprise determining whether a renal injury in a subject is prerenal, intrinsic renal, or postrenal; and/or further subdividing these classes into subclasses such as acute tubular injury, acute glomerulonephritis acute tubulointerstitial nephritis, acute vascular nephropathy, or infiltrative disease; and/or assigning a likelihood that a subject will progress to a particular RIFLE stage, and the assay result(s) is/are correlated to the injury classification for the subject. For example, the measured concentration may be compared to a threshold value, and when the measured concentration is above the threshold, a particular classification is assigned; alternatively, when the measured concentration is below the threshold, a different classification may be assigned to the subject.


A variety of methods may be used by the skilled artisan to arrive at a desired threshold value for use in these methods. For example, the threshold value may be determined from a population of normal subjects by selecting a concentration representing the 75th, 85th, 90th, 95th, or 99th percentile of a kidney injury marker measured in such normal subjects. Alternatively, the threshold value may be determined from a “diseased” population of subjects, e.g., those suffering from an injury or having a predisposition for an injury (e.g., progression to ARF or some other clinical outcome such as death, dialysis, renal transplantation, etc.), by selecting a concentration representing the 75th, 85th, 90th, 95th, or 99th percentile of a kidney injury marker measured in such subjects. In another alternative, the threshold value may be determined from a prior measurement of a kidney injury marker in the same subject; that is, a temporal change in the level of a kidney injury marker in the subject may be used to assign risk to the subject.


The foregoing discussion is not meant to imply, however, that the kidney injury markers of the present invention must be compared to corresponding individual thresholds. Methods for combining assay results can comprise the use of multivariate logistical regression, loglinear modeling, neural network analysis, n-of-m analysis, decision tree analysis, calculating ratios of markers, etc. This list is not meant to be limiting. In these methods, a composite result which is determined by combining individual markers may be treated as if it is itself a marker; that is, a threshold may be determined for the composite result as described herein for individual markers, and the composite result for an individual patient compared to this threshold.


The ability of a particular test to distinguish two populations can be established using ROC analysis. For example, ROC curves established from a “first” subpopulation which is predisposed to one or more future changes in renal status, and a “second” subpopulation which is not so predisposed can be used to calculate a ROC curve, and the area under the curve provides a measure of the quality of the test. Preferably, the tests described herein provide a ROC curve area greater than 0.5, preferably at least 0.6, more preferably 0.7, still more preferably at least 0.8, even more preferably at least 0.9, and most preferably at least 0.95.


In certain aspects, the measured concentration of one or more kidney injury markers, or a composite of such markers, may be treated as continuous variables. For example, any particular concentration can be converted into a corresponding probability of a future reduction in renal function for the subject, the occurrence of an injury, a classification, etc. In yet another alternative, a threshold that can provide an acceptable level of specificity and sensitivity in separating a population of subjects into “bins” such as a “first” subpopulation (e.g., which is predisposed to one or more future changes in renal status, the occurrence of an injury, a classification, etc.) and a “second” subpopulation which is not so predisposed. A threshold value is selected to separate this first and second population by one or more of the following measures of test accuracy:


an odds ratio greater than 1, preferably at least about 2 or more or about 0.5 or less, more preferably at least about 3 or more or about 0.33 or less, still more preferably at least about 4 or more or about 0.25 or less, even more preferably at least about 5 or more or about 0.2 or less, and most preferably at least about 10 or more or about 0.1 or less;


a specificity of greater than 0.5, preferably at least about 0.6, more preferably at least about 0.7, still more preferably at least about 0.8, even more preferably at least about 0.9 and most preferably at least about 0.95, with a corresponding sensitivity greater than 0.2, preferably greater than about 0.3, more preferably greater than about 0.4, still more preferably at least about 0.5, even more preferably about 0.6, yet more preferably greater than about 0.7, still more preferably greater than about 0.8, more preferably greater than about 0.9, and most preferably greater than about 0.95;


a sensitivity of greater than 0.5, preferably at least about 0.6, more preferably at least about 0.7, still more preferably at least about 0.8, even more preferably at least about 0.9 and most preferably at least about 0.95, with a corresponding specificity greater than 0.2, preferably greater than about 0.3, more preferably greater than about 0.4, still more preferably at least about 0.5, even more preferably about 0.6, yet more preferably greater than about 0.7, still more preferably greater than about 0.8, more preferably greater than about 0.9, and most preferably greater than about 0.95;


at least about 75% sensitivity, combined with at least about 75% specificity;


a positive likelihood ratio (calculated as sensitivity/(1-specificity)) of greater than 1, at least about 2, more preferably at least about 3, still more preferably at least about 5, and most preferably at least about 10; or


a negative likelihood ratio (calculated as (1-sensitivity)/specificity) of less than 1, less than or equal to about 0.5, more preferably less than or equal to about 0.3, and most preferably less than or equal to about 0.1.


The term “about” in the context of any of the above measurements refers to +/−5% of a given measurement.


Multiple thresholds may also be used to assess renal status in a subject. For example, a “first” subpopulation which is predisposed to one or more future changes in renal status, the occurrence of an injury, a classification, etc., and a “second” subpopulation which is not so predisposed can be combined into a single group. This group is then subdivided into three or more equal parts (known as tertiles, quartiles, quintiles, etc., depending on the number of subdivisions). An odds ratio is assigned to subjects based on which subdivision they fall into. If one considers a tertile, the lowest or highest tertile can be used as a reference for comparison of the other subdivisions. This reference subdivision is assigned an odds ratio of 1. The second tertile is assigned an odds ratio that is relative to that first tertile. That is, someone in the second tertile might be 3 times more likely to suffer one or more future changes in renal status in comparison to someone in the first tertile. The third tertile is also assigned an odds ratio that is relative to that first tertile.


In certain embodiments, the assay method is an immunoassay. Antibodies for use in such assays will specifically bind a full length kidney injury marker of interest, and may also bind one or more polypeptides that are “related” thereto, as that term is defined hereinafter. Numerous immunoassay formats are known to those of skill in the art. Preferred body fluid samples are selected from the group consisting of urine, blood, serum, saliva, tears, and plasma. In the case of those kidney injury markers which are membrane proteins as described hereinafter, preferred assays detect soluble forms thereof.


The foregoing method steps should not be interpreted to mean that the kidney injury marker assay result(s) is/are used in isolation in the methods described herein. Rather, additional variables or other clinical indicia may be included in the methods described herein. For example, a risk stratification, diagnostic, classification, monitoring, etc. method may combine the assay result(s) with one or more variables measured for the subject selected from the group consisting of demographic information (e.g., weight, sex, age, race), medical history (e.g., family history, type of surgery, pre-existing disease such as aneurism, congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, or sepsis, type of toxin exposure such as NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin), clinical variables (e.g., blood pressure, temperature, respiration rate), risk scores (APACHE score, PREDICT score, TIMI Risk Score for UA/NSTEMI, Framingham Risk Score, risk scores of Thakar et al. (J. Am. Soc. Nephrol. 16: 162-68, 2005), Mehran et al. (J. Am. Coll. Cardiol. 44: 1393-99, 2004), Wijeysundera et al. (JAMA 297: 1801-9, 2007), Goldstein and Chawla (Clin. J. Am. Soc. Nephrol. 5: 943-49, 2010), or Chawla et al. (Kidney Intl. 68: 2274-80, 2005)), a glomerular filtration rate, an estimated glomerular filtration rate, a urine production rate, a serum or plasma creatinine concentration, a urine creatinine concentration, a fractional excretion of sodium, a urine sodium concentration, a urine creatinine to serum or plasma creatinine ratio, a urine specific gravity, a urine osmolality, a urine urea nitrogen to plasma urea nitrogen ratio, a plasma BUN to creatnine ratio, a renal failure index calculated as urine sodium/(urine creatinine/plasma creatinine), a serum or plasma neutrophil gelatinase (NGAL) concentration, a urine NGAL concentration, a serum or plasma cystatin C concentration, a serum or plasma cardiac troponin concentration, a serum or plasma BNP concentration, a serum or plasma NTproBNP concentration, and a serum or plasma proBNP concentration. Other measures of renal function which may be combined with one or more kidney injury marker assay result(s) are described hereinafter and in Harrison's Principles of Internal Medicine, 17th Ed., McGraw Hill, N.Y., pages 1741-1830, and Current Medical Diagnosis & Treatment 2008, 47th Ed, McGraw Hill, N.Y., pages 785-815, each of which are hereby incorporated by reference in their entirety.


When more than one marker is measured, the individual markers may be measured in samples obtained at the same time, or may be determined from samples obtained at different (e.g., an earlier or later) times. The individual markers may also be measured on the same or different body fluid samples. For example, one kidney injury marker may be measured in a serum or plasma sample and another kidney injury marker may be measured in a urine sample. In addition, assignment of a likelihood may combine an individual kidney injury marker assay result with temporal changes in one or more additional variables.


In various related aspects, the present invention also relates to devices and kits for performing the methods described herein. Suitable kits comprise reagents sufficient for performing an assay for at least one of the described kidney injury markers, together with instructions for performing the described threshold comparisons.


In certain embodiments, reagents for performing such assays are provided in an assay device, and such assay devices may be included in such a kit. Preferred reagents can comprise one or more solid phase antibodies, the solid phase antibody comprising antibody that detects the intended biomarker target(s) bound to a solid support. In the case of sandwich immunoassays, such reagents can also include one or more detectably labeled antibodies, the detectably labeled antibody comprising antibody that detects the intended biomarker target(s) bound to a detectable label. Additional optional elements that may be provided as part of an assay device are described hereinafter.


Detectable labels may include molecules that are themselves detectable (e.g., fluorescent moieties, electrochemical labels, ecl (electrochemical luminescence) labels, metal chelates, colloidal metal particles, etc.) as well as molecules that may be indirectly detected by production of a detectable reaction product (e.g., enzymes such as horseradish peroxidase, alkaline phosphatase, etc.) or through the use of a specific binding molecule which itself may be detectable (e.g., a labeled antibody that binds to the second antibody, biotin, digoxigenin, maltose, oligohistidine, 2,4-dintrobenzene, phenylarsenate, ssDNA, dsDNA, etc.).


Generation of a signal from the signal development element can be performed using various optical, acoustical, and electrochemical methods well known in the art. Examples of detection modes include fluorescence, radiochemical detection, reflectance, absorbance, amperometry, conductance, impedance, interferometry, ellipsometry, etc. In certain of these methods, the solid phase antibody is coupled to a transducer (e.g., a diffraction grating, electrochemical sensor, etc) for generation of a signal, while in others, a signal is generated by a transducer that is spatially separate from the solid phase antibody (e.g., a fluorometer that employs an excitation light source and an optical detector). This list is not meant to be limiting. Antibody-based biosensors may also be employed to determine the presence or amount of analytes that optionally eliminate the need for a labeled molecule.







DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to methods and compositions for diagnosis, differential diagnosis, risk stratification, monitoring, classifying and determination of treatment regimens in subjects suffering or at risk of suffering from injury to renal function, reduced renal function and/or acute renal failure through measurement of one or more kidney injury markers. In various embodiments, a measured concentration of one or more biomarkers selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator or one or more markers related thereto, are correlated to the renal status of the subject.


For purposes of this document, the following definitions apply:


As used herein, an “injury to renal function” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) measurable reduction in a measure of renal function. Such an injury may be identified, for example, by a decrease in glomerular filtration rate or estimated GFR, a reduction in urine output, an increase in serum creatinine, an increase in serum cystatin C, a requirement for renal replacement therapy, etc “Improvement in Renal Function” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) measurable increase in a measure of renal function. Preferred methods for measuring and/or estimating GFR are described hereinafter.


As used herein, “reduced renal function” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) reduction in kidney function identified by an absolute increase in serum creatinine of greater than or equal to 0.1 mg/dL (≧8.8 mmol/L), a percentage increase in serum creatinine of greater than or equal to 20% (1.2-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour).


As used herein, “acute renal failure” or “ARF” is an abrupt (within 14 days, preferably within 7 days, more preferably within 72 hours, and still more preferably within 48 hours) reduction in kidney function identified by an absolute increase in serum creatinine of greater than or equal to 0.3 mg/dl (≧26.4 mmol/l), a percentage increase in serum creatinine of greater than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for at least 6 hours). This term is synonymous with “acute kidney injury” or “AKI.”


As used herein, the term “Serum albumin” refers to one or more polypeptides present in a biological sample that are derived from the Prolactin precursor (human precursor: Swiss-Prot P02768 (SEQ ID NO: 1))










        10         20         30         40         50         60



MKWVTFISLL FLFSSAYSRG VFRRDAHKSE VAHRFKDLGE ENFKALVLIA FAQYLQQCPF





        70         80         90        100        110        120


EDHVKLVNEV TEFAKTCVAD ESAENCDKSL HTLFGDKLCT VATLRETYGE MADCCAKQEP





       130        140        150        160        170        180


ERNECFLQHK DDNPNLPRLV RPEVDVMCTA FHDNEETFLK KYLYEIARRH PYFYAPELLF





       190        200        210        220        230        240


FAKRYKAAFT ECCQAADKAA CLLPKLDELR DEGKASSAKQ RLKCASLQKF GERAFKAWAV





       250        260        270        280        290        300


ARLSQRFPKA EFAEVSKLVT DLTKVHTECC HGDLLECADD RADLAKYICE NQDSISSKLK





       310        320        330        340        350        360


ECCEKPLLEK SHCIAEVEND EMPADLPSLA ADFVESKDVC KNYAEAKDVF LGMFLYEYAR





       370        380        390        400        410        420


RHPDYSVVLL LRLAKTYETT LEKCCAAADP HECYAKVFDE FKPLVEEPQN LIKQNCELFE





       430        440        450        460        470        480


QLGEYKFQNA LLVRYTKKVP QVSTPTLVEV SRNLGKVGSK CCKHPEAKRM PCAEDYLSVV





       490        500        510        520        530        540


LNQLCVLHEK TPVSDRVTKC CTESLVNRRP CFSALEVDET YVPKEFNAET FTFHADICTL





       550        560        570        580        590        600


SEKERQIKKQ TALVELVKHK PKATKEQLKA VMDDFAAFVE KCCKADDKET CFAEEGKKLV





AASQAALGL






The following domains have been identified in Serum Albumin:

















Residues
Length
Domain ID




















1-18
18
Signal peptide



19-22 
4
Activation peptide



25-609
585
Serum Albumin










As used herein, the term “Protein S100-B” refers to one or more polypeptides present in a biological sample that are derived from the Protein S100-B precursor (human precursor: Swiss-Prot P04271 (SEQ ID NO: 2))










        10         20         30         40         50         60



MSELEKAMVA LIDVFHQYSG REGDKHKLKK SELKELINNE LSHFLEEIKE QEVVDKVMET





        70         80         90


LDNDGDGECD FQEFMAFVAM VTTACHEFFE HE






The following domains have been identified in Protein S100-B:

















Residues
Length
Domain ID




















1
1
Initiator methionine



2-92
91
Protein S100-B










As used herein, the term “Resistin” refers to one or more polypeptides present in a biological sample that are derived from the Resistin precursor (human precursor: Swiss-Prot Q9HD89 (SEQ ID NO: 3))










        10         20         30         40         50         60



MKALCLLLLP VLGLLVSSKT LCSMEEAINE RIQEVAGSLI FRAISSIGLE CQSVTSRGDL





        70         80         90        100


ATCPRGFAVT GCTCGSACGS WDVRAETTCH CQCAGMDWTG ARCCRVQP






The following domains have been identified in Resistin:

















Residues
Length
Domain ID









1-18
18
Signal peptide



19-108
90
Resistin










As used herein, the term “Serum amyloid A protein” refers to one or more polypeptides present in a biological sample that are derived from the Serum amyloid A protein precursor (human precursor: Swiss-Prot P02735 (SEQ ID NO: 4))










        10         20         30         40         50         60



MKLLTGLVFC SLVLGVSSRS FFSFLGEAFD GARDMWRAYS DMREANYIGS DKYFHARGNY





        70         80         90        100        110        120


DAAKRGPGGV WAAEAISDAR ENIQRFFGHG AEDSLADQAA NEWGRSGKDP NHFRPAGLPE






The following domains have been identified in Serum amyloid A protein:

















Residues
Length
Domain ID




















1-18
18
Signal peptide



19-122
104
Serum amyloid A protein



19-94 
76
Amyloid A protein



20-122
103
Serum amyloid A protein (2-104)



20-121
102
Serum amyloid A protein (2-103)



20-120
101
Serum amyloid A protein (2-102)



21-122
102
Serum amyloid A protein (3-104)



22-119
98
Serum amyloid A protein (4-101)










As used herein, the term “Parathyroid hormone” refers to one or more polypeptides present in a biological sample that are derived from Parathyroid hormone precursor (human precursor: Swiss-Prot P01270 (SEQ ID NO: 5))










        10         20         30         40         50         60



MIPAKDMAKV MIVMLAICFL TKSDGKSVKK RSVSEIQLMH NLGKHLNSME RVEWLRKKLQ





        70         80         90        100        110


DVHNFVALGA PLAPRDAGSQ RPRKKEDNVL VESHEKSLGE ADKADVNVLT KAKSQ






The following domains have been identified in Parathyroid hormone:

















Residues
Length
Domain ID




















1-25
25
Signal peptide



26-31 
6
Propeptide



32-115
84
Parathyroid hormone










As used herein, the term “Tissue-type plasminogen activator” refers to one or more polypeptides present in a biological sample that are derived from Tissue-type plasminogen activator precursor (human precursor: Swiss-Prot P00750 (SEQ ID NO: 6))










        10         20         30         40         50         60



MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY QQHQSWLRPV





        70         80         90        100        110        120


LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA LYFSDFVCQC PEGFAGKCCE





       130        140        150        160        170        180


IDTRATCYED QGISYRGTWS TAESGAECTN WNSSALAQKP YSGRRPDAIR LGLGNHNYCR





       190        200        210        220        230        240


NPDRDSKPWC YVFKAGKYSS EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN





       250        260        270        280        290        300


SMILIGKVYT AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG





       310        320        330        340        350        360


LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC WILSAAHCFQ





       370        380        390        400        410        420


ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD DTYDNDIALL QLKSDSSRCA





       430        440        450        460        470        480


QESSVVRTVC LPPADLQLPD WTECELSGYG KHEALSPFYS ERLKEAHVRL YPSSRCTSQH





       490        500        510        520        530        540


LLNRTVTDNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK





       550        560


DVPGVYTKVT NYLDWIRDNM RP






The following domains have been identified in Tissue-type plasminogen activator:














Residues
Length
Domain ID

















 1-22
22
Signal peptide





23-32
10
Propeptide





33-35
3
Propeptide





 36-562
527
Tissue-type plasminogen activator





 36-310
275
Tissue-type plasminogen activator




chain A





311-562
252
Tissue-type plasminogen activator




chain B





169-291

→ TGRSVSSPATASMRPCPLSIRSG




(SEQ ID NO: 7) in isoform 2





292-562

missing in isoform 2





39-85

→ G in isoform 3





 1-40

→ MAS in isoform 4





 79-208

missing in isoform 4









As used herein, the term “Glial cell line-derived neurotrophic factor” refers to one or more polypeptides present in a biological sample that are derived from Glial cell line-derived neurotrophic factor precursor (human precursor: Swiss-Prot P39905 (SEQ ID NO: 8))










        10         20         30         40         50         60



MKLWDVVAVC LVLLHTASAF PLPAGKRPPE APAEDRSLGR RRAPFALSSD SNMPEDYPDQ





        70         80         90        100        110        120


FDDVMDFIQA TIKRLKRSPD KQMAVLPRRE RNRQAAAANP ENSRGKGRRG QRGKNRGCVL





       130        140        150        160        170        180


TAIHLNVTDL GLGYETKEEL IFRYCSGSCD AAETTYDKIL KNLSRNRRLV SDKVGQACCR





       190        200        210


PIAFDDDLSF LDDNLVYHIL RKHSAKRCGC I






The following domains have been identified in Glial cell line-derived neurotrophic factor:














Residues
Length
Domain ID

















 1-19
19
Signal peptide





20-75
56
Propeptide





 78-211
134
Glial cell line-derived neurotrophic




factor





1

→ MQSLPNSNGAAAGRDFKM (SEQ




ID NO: 9) in isoforms 3 and 4





25-51

→ A in isoforms 2 and 4









As used herein, the term “relating a signal to the presence or amount” of an analyte reflects the following understanding. Assay signals are typically related to the presence or amount of an analyte through the use of a standard curve calculated using known concentrations of the analyte of interest. As the term is used herein, an assay is “configured to detect” an analyte if an assay can generate a detectable signal indicative of the presence or amount of a physiologically relevant concentration of the analyte. Because an antibody epitope is on the order of 8 amino acids, an immunoassay configured to detect a marker of interest will also detect polypeptides related to the marker sequence, so long as those polypeptides contain the epitope(s) necessary to bind to the antibody or antibodies used in the assay. The term “related marker” as used herein with regard to a biomarker such as one of the kidney injury markers described herein refers to one or more fragments, variants, etc., of a particular marker or its biosynthetic parent that may be detected as a surrogate for the marker itself or as independent biomarkers. The term also refers to one or more polypeptides present in a biological sample that are derived from the biomarker precursor complexed to additional species, such as binding proteins, receptors, heparin, lipids, sugars, etc.


In this regard, the skilled artisan will understand that the signals obtained from an immunoassay are a direct result of complexes formed between one or more antibodies and the target biomolecule (i.e., the analyte) and polypeptides containing the necessary epitope(s) to which the antibodies bind. While such assays may detect the full length biomarker and the assay result be expressed as a concentration of a biomarker of interest, the signal from the assay is actually a result of all such “immunoreactive” polypeptides present in the sample. Expression of biomarkers may also be determined by means other than immunoassays, including protein measurements (such as dot blots, western blots, chromatographic methods, mass spectrometry, etc.) and nucleic acid measurements (mRNA quatitation). This list is not meant to be limiting.


As used herein, the term “hydrocortisone” (also known as cortisol) refers to (11β)-11,17,21-trihydroxypregn-4-ene-3,20-dione. Hydrocortisone is a steroid hormone, or glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein and carbohydrate metabolism.


The term “positive going” marker as that term is used herein refer to a marker that is determined to be elevated in subjects suffering from a disease or condition, relative to subjects not suffering from that disease or condition. The term “negative going” marker as that term is used herein refer to a marker that is determined to be reduced in subjects suffering from a disease or condition, relative to subjects not suffering from that disease or condition.


The term “subject” as used herein refers to a human or non-human organism. Thus, the methods and compositions described herein are applicable to both human and veterinary disease. Further, while a subject is preferably a living organism, the invention described herein may be used in post-mortem analysis as well. Preferred subjects are humans, and most preferably “patients,” which as used herein refers to living humans that are receiving medical care for a disease or condition. This includes persons with no defined illness who are being investigated for signs of pathology.


Preferably, an analyte is measured in a sample. Such a sample may be obtained from a subject, or may be obtained from biological materials intended to be provided to the subject. For example, a sample may be obtained from a kidney being evaluated for possible transplantation into a subject, and an analyte measurement used to evaluate the kidney for preexisting damage. Preferred samples are body fluid samples.


The term “body fluid sample” as used herein refers to a sample of bodily fluid obtained for the purpose of diagnosis, prognosis, classification or evaluation of a subject of interest, such as a patient or transplant donor. In certain embodiments, such a sample may be obtained for the purpose of determining the outcome of an ongoing condition or the effect of a treatment regimen on a condition. Preferred body fluid samples include blood, serum, plasma, cerebrospinal fluid, urine, saliva, sputum, and pleural effusions. In addition, one of skill in the art would realize that certain body fluid samples would be more readily analyzed following a fractionation or purification procedure, for example, separation of whole blood into serum or plasma components.


The term “diagnosis” as used herein refers to methods by which the skilled artisan can estimate and/or determine the probability (“a likelihood”) of whether or not a patient is suffering from a given disease or condition. In the case of the present invention, “diagnosis” includes using the results of an assay, most preferably an immunoassay, for a kidney injury marker of the present invention, optionally together with other clinical characteristics, to arrive at a diagnosis (that is, the occurrence or nonoccurrence) of an acute renal injury or ARF for the subject from which a sample was obtained and assayed. That such a diagnosis is “determined” is not meant to imply that the diagnosis is 100% accurate. Many biomarkers are indicative of multiple conditions. The skilled clinician does not use biomarker results in an informational vacuum, but rather test results are used together with other clinical indicia to arrive at a diagnosis. Thus, a measured biomarker level on one side of a predetermined diagnostic threshold indicates a greater likelihood of the occurrence of disease in the subject relative to a measured level on the other side of the predetermined diagnostic threshold.


Similarly, a prognostic risk signals a probability (“a likelihood”) that a given course or outcome will occur. A level or a change in level of a prognostic indicator, which in turn is associated with an increased probability of morbidity (e.g., worsening renal function, future ARF, or death) is referred to as being “indicative of an increased likelihood” of an adverse outcome in a patient.


Marker Assays


In general, immunoassays involve contacting a sample containing or suspected of containing a biomarker of interest with at least one antibody that specifically binds to the biomarker. A signal is then generated indicative of the presence or amount of complexes formed by the binding of polypeptides in the sample to the antibody. The signal is then related to the presence or amount of the biomarker in the sample. Numerous methods and devices are well known to the skilled artisan for the detection and analysis of biomarkers. See, e.g., U.S. Pat. Nos. 6,143,576; 6,113,855; 6,019,944; 5,985,579; 5,947,124; 5,939,272; 5,922,615; 5,885,527; 5,851,776; 5,824,799; 5,679,526; 5,525,524; and 5,480,792, and The Immunoassay Handbook, David Wild, ed. Stockton Press, New York, 1994, each of which is hereby incorporated by reference in its entirety, including all tables, figures and claims.


The assay devices and methods known in the art can utilize labeled molecules in various sandwich, competitive, or non-competitive assay formats, to generate a signal that is related to the presence or amount of the biomarker of interest. Suitable assay formats also include chromatographic, mass spectrographic, and protein “blotting” methods. Additionally, certain methods and devices, such as biosensors and optical immunoassays, may be employed to determine the presence or amount of analytes without the need for a labeled molecule. See, e.g., U.S. Pat. Nos. 5,631,171; and 5,955,377, each of which is hereby incorporated by reference in its entirety, including all tables, figures and claims. One skilled in the art also recognizes that robotic instrumentation including but not limited to Beckman ACCESS®, Abbott AXSYM®, Roche ELECSYS®, Dade Behring STRATUS® systems are among the immunoassay analyzers that are capable of performing immunoassays. But any suitable immunoassay may be utilized, for example, enzyme-linked immunoassays (ELISA), radioimmunoassays (RIAs), competitive binding assays, and the like.


Antibodies or other polypeptides may be immobilized onto a variety of solid supports for use in assays. Solid phases that may be used to immobilize specific binding members include those developed and/or used as solid phases in solid phase binding assays. Examples of suitable solid phases include membrane filters, cellulose-based papers, beads (including polymeric, latex and paramagnetic particles), glass, silicon wafers, microparticles, nanoparticles, TentaGels, AgroGels, PEGA gels, SPOCC gels, and multiple-well plates. An assay strip could be prepared by coating the antibody or a plurality of antibodies in an array on solid support. This strip could then be dipped into the test sample and then processed quickly through washes and detection steps to generate a measurable signal, such as a colored spot. Antibodies or other polypeptides may be bound to specific zones of assay devices either by conjugating directly to an assay device surface, or by indirect binding. In an example of the later case, antibodies or other polypeptides may be immobilized on particles or other solid supports, and that solid support immobilized to the device surface.


Biological assays require methods for detection, and one of the most common methods for quantitation of results is to conjugate a detectable label to a protein or nucleic acid that has affinity for one of the components in the biological system being studied. Detectable labels may include molecules that are themselves detectable (e.g., fluorescent moieties, electrochemical labels, metal chelates, etc.) as well as molecules that may be indirectly detected by production of a detectable reaction product (e.g., enzymes such as horseradish peroxidase, alkaline phosphatase, etc.) or by a specific binding molecule which itself may be detectable (e.g., biotin, digoxigenin, maltose, oligohistidine, 2,4-dintrobenzene, phenylarsenate, ssDNA, dsDNA, etc.).


Preparation of solid phases and detectable label conjugates often comprise the use of chemical cross-linkers. Cross-linking reagents contain at least two reactive groups, and are divided generally into homofunctional cross-linkers (containing identical reactive groups) and heterofunctional cross-linkers (containing non-identical reactive groups). Homobifunctional cross-linkers that couple through amines, sulfhydryls or react non-specifically are available from many commercial sources. Maleimides, alkyl and aryl halides, alpha-haloacyls and pyridyl disulfides are thiol reactive groups. Maleimides, alkyl and aryl halides, and alpha-haloacyls react with sulfhydryls to form thiol ether bonds, while pyridyl disulfides react with sulfhydryls to produce mixed disulfides. The pyridyl disulfide product is cleavable. Imidoesters are also very useful for protein-protein cross-links. A variety of heterobifunctional cross-linkers, each combining different attributes for successful conjugation, are commercially available.


In certain aspects, the present invention provides kits for the analysis of the described kidney injury markers. The kit comprises reagents for the analysis of at least one test sample which comprise at least one antibody that a kidney injury marker. The kit can also include devices and instructions for performing one or more of the diagnostic and/or prognostic correlations described herein. Preferred kits will comprise an antibody pair for performing a sandwich assay, or a labeled species for performing a competitive assay, for the analyte. Preferably, an antibody pair comprises a first antibody conjugated to a solid phase and a second antibody conjugated to a detectable label, wherein each of the first and second antibodies that bind a kidney injury marker. Most preferably each of the antibodies are monoclonal antibodies. The instructions for use of the kit and performing the correlations can be in the form of labeling, which refers to any written or recorded material that is attached to, or otherwise accompanies a kit at any time during its manufacture, transport, sale or use. For example, the term labeling encompasses advertising leaflets and brochures, packaging materials, instructions, audio or video cassettes, computer discs, as well as writing imprinted directly on kits.


Antibodies


The term “antibody” as used herein refers to a peptide or polypeptide derived from, modeled after or substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, capable of specifically binding an antigen or epitope. See, e.g. Fundamental Immunology, 3rd Edition, W. E. Paul, ed., Raven Press, N.Y. (1993); Wilson (1994; J. Immunol. Methods 175:267-273; Yarmush (1992) J. Biochem. Biophys. Methods 25:85-97. The term antibody includes antigen-binding portions, i.e., “antigen binding sites,” (e.g., fragments, subsequences, complementarity determining regions (CDRs)) that retain capacity to bind antigen, including (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab′)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR). Single chain antibodies are also included by reference in the term “antibody.”


Antibodies used in the immunoassays described herein preferably specifically bind to a kidney injury marker of the present invention. The term “specifically binds” is not intended to indicate that an antibody binds exclusively to its intended target since, as noted above, an antibody binds to any polypeptide displaying the epitope(s) to which the antibody binds. Rather, an antibody “specifically binds” if its affinity for its intended target is about 5-fold greater when compared to its affinity for a non-target molecule which does not display the appropriate epitope(s). Preferably the affinity of the antibody will be at least about 5 fold, preferably 10 fold, more preferably 25-fold, even more preferably 50-fold, and most preferably 100-fold or more, greater for a target molecule than its affinity for a non-target molecule. In preferred embodiments, Preferred antibodies bind with affinities of at least about 107 M−1, and preferably between about 108 M−1 to about 109 M−1, about 109 M−1 to about 1010 M−1 or about 1010 M−1 to about 1012 M−1.


Affinity is calculated as Kd=koff/kon (koff is the dissociation rate constant, Kon is the association rate constant and Kd is the equilibrium constant). Affinity can be determined at equilibrium by measuring the fraction bound (r) of labeled ligand at various concentrations (c). The data are graphed using the Scatchard equation: r/c=K(n−r): where r=moles of bound ligand/mole of receptor at equilibrium; c=free ligand concentration at equilibrium; K=equilibrium association constant; and n=number of ligand binding sites per receptor molecule. By graphical analysis, r/c is plotted on the Y-axis versus r on the X-axis, thus producing a Scatchard plot. Antibody affinity measurement by Scatchard analysis is well known in the art. See, e.g., van Erp et al., J. Immunoassay 12: 425-43, 1991; Nelson and Griswold, Comput. Methods Programs Biomed. 27: 65-8, 1988.


The term “epitope” refers to an antigenic determinant capable of specific binding to an antibody. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. Conformational and nonconformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents.


Numerous publications discuss the use of phage display technology to produce and screen libraries of polypeptides for binding to a selected analyte. See, e.g, Cwirla et al., Proc. Natl. Acad. Sci. USA 87, 6378-82, 1990; Devlin et al., Science 249, 404-6, 1990, Scott and Smith, Science 249, 386-88, 1990; and Ladner et al., U.S. Pat. No. 5,571,698. A basic concept of phage display methods is the establishment of a physical association between DNA encoding a polypeptide to be screened and the polypeptide. This physical association is provided by the phage particle, which displays a polypeptide as part of a capsid enclosing the phage genome which encodes the polypeptide. The establishment of a physical association between polypeptides and their genetic material allows simultaneous mass screening of very large numbers of phage bearing different polypeptides. Phage displaying a polypeptide with affinity to a target bind to the target and these phage are enriched by affinity screening to the target. The identity of polypeptides displayed from these phage can be determined from their respective genomes. Using these methods a polypeptide identified as having a binding affinity for a desired target can then be synthesized in bulk by conventional means. See, e.g., U.S. Pat. No. 6,057,098, which is hereby incorporated in its entirety, including all tables, figures, and claims.


The antibodies that are generated by these methods may then be selected by first screening for affinity and specificity with the purified polypeptide of interest and, if required, comparing the results to the affinity and specificity of the antibodies with polypeptides that are desired to be excluded from binding. The screening procedure can involve immobilization of the purified polypeptides in separate wells of microtiter plates. The solution containing a potential antibody or groups of antibodies is then placed into the respective microtiter wells and incubated for about 30 min to 2 h. The microtiter wells are then washed and a labeled secondary antibody (for example, an anti-mouse antibody conjugated to alkaline phosphatase if the raised antibodies are mouse antibodies) is added to the wells and incubated for about 30 min and then washed. Substrate is added to the wells and a color reaction will appear where antibody to the immobilized polypeptide(s) are present.


The antibodies so identified may then be further analyzed for affinity and specificity in the assay design selected. In the development of immunoassays for a target protein, the purified target protein acts as a standard with which to judge the sensitivity and specificity of the immunoassay using the antibodies that have been selected. Because the binding affinity of various antibodies may differ; certain antibody pairs (e.g., in sandwich assays) may interfere with one another sterically, etc., assay performance of an antibody may be a more important measure than absolute affinity and specificity of an antibody.


While the present application describes antibody-based binding assays in detail, alternatives to antibodies as binding species in assays are well known in the art. These include receptors for a particular target, aptamers, etc. Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist. High-affinity aptamers containing modified nucleotides conferring improved characteristics on the ligand, such as improved in vivo stability or improved delivery characteristics. Examples of such modifications include chemical substitutions at the ribose and/or phosphate and/or base positions, and may include amino acid side chain functionalities.


Assay Correlations


The term “correlating” as used herein in reference to the use of biomarkers refers to comparing the presence or amount of the biomarker(s) in a patient to its presence or amount in persons known to suffer from, or known to be at risk of, a given condition; or in persons known to be free of a given condition. Often, this takes the form of comparing an assay result in the form of a biomarker concentration to a predetermined threshold selected to be indicative of the occurrence or nonoccurrence of a disease or the likelihood of some future outcome.


Selecting a diagnostic threshold involves, among other things, consideration of the probability of disease, distribution of true and false diagnoses at different test thresholds, and estimates of the consequences of treatment (or a failure to treat) based on the diagnosis. For example, when considering administering a specific therapy which is highly efficacious and has a low level of risk, few tests are needed because clinicians can accept substantial diagnostic uncertainty. On the other hand, in situations where treatment options are less effective and more risky, clinicians often need a higher degree of diagnostic certainty. Thus, cost/benefit analysis is involved in selecting a diagnostic threshold.


Suitable thresholds may be determined in a variety of ways. For example, one recommended diagnostic threshold for the diagnosis of acute myocardial infarction using cardiac troponin is the 97.5 th percentile of the concentration seen in a normal population. Another method may be to look at serial samples from the same patient, where a prior “baseline” result is used to monitor for temporal changes in a biomarker level.


Population studies may also be used to select a decision threshold. Receiver Operating Characteristic (“ROC”) arose from the field of signal detection theory developed during World War II for the analysis of radar images, and ROC analysis is often used to select a threshold able to best distinguish a “diseased” subpopulation from a “nondiseased” subpopulation. A false positive in this case occurs when the person tests positive, but actually does not have the disease. A false negative, on the other hand, occurs when the person tests negative, suggesting they are healthy, when they actually do have the disease. To draw a ROC curve, the true positive rate (TPR) and false positive rate (FPR) are determined as the decision threshold is varied continuously. Since TPR is equivalent with sensitivity and FPR is equal to 1−specificity, the ROC graph is sometimes called the sensitivity vs (1-specificity) plot. A perfect test will have an area under the ROC curve of 1.0; a random test will have an area of 0.5. A threshold is selected to provide an acceptable level of specificity and sensitivity.


In this context, “diseased” is meant to refer to a population having one characteristic (the presence of a disease or condition or the occurrence of some outcome) and “nondiseased” is meant to refer to a population lacking the characteristic. While a single decision threshold is the simplest application of such a method, multiple decision thresholds may be used. For example, below a first threshold, the absence of disease may be assigned with relatively high confidence, and above a second threshold the presence of disease may also be assigned with relatively high confidence. Between the two thresholds may be considered indeterminate. This is meant to be exemplary in nature only.


In addition to threshold comparisons, other methods for correlating assay results to a patient classification (occurrence or nonoccurrence of disease, likelihood of an outcome, etc.) include decision trees, rule sets, Bayesian methods, and neural network methods. These methods can produce probability values representing the degree to which a subject belongs to one classification out of a plurality of classifications.


Measures of test accuracy may be obtained as described in Fischer et al., Intensive Care Med. 29: 1043-51, 2003, and used to determine the effectiveness of a given biomarker. These measures include sensitivity and specificity, predictive values, likelihood ratios, diagnostic odds ratios, and ROC curve areas. The area under the curve (“AUC”) of a ROC plot is equal to the probability that a classifier will rank a randomly chosen positive instance higher than a randomly chosen negative one. The area under the ROC curve may be thought of as equivalent to the Mann-Whitney U test, which tests for the median difference between scores obtained in the two groups considered if the groups are of continuous data, or to the Wilcoxon test of ranks.


As discussed above, suitable tests may exhibit one or more of the following results on these various measures: a specificity of greater than 0.5, preferably at least 0.6, more preferably at least 0.7, still more preferably at least 0.8, even more preferably at least 0.9 and most preferably at least 0.95, with a corresponding sensitivity greater than 0.2, preferably greater than 0.3, more preferably greater than 0.4, still more preferably at least 0.5, even more preferably 0.6, yet more preferably greater than 0.7, still more preferably greater than 0.8, more preferably greater than 0.9, and most preferably greater than 0.95; a sensitivity of greater than 0.5, preferably at least 0.6, more preferably at least 0.7, still more preferably at least 0.8, even more preferably at least 0.9 and most preferably at least 0.95, with a corresponding specificity greater than 0.2, preferably greater than 0.3, more preferably greater than 0.4, still more preferably at least 0.5, even more preferably 0.6, yet more preferably greater than 0.7, still more preferably greater than 0.8, more preferably greater than 0.9, and most preferably greater than 0.95; at least 75% sensitivity, combined with at least 75% specificity; a ROC curve area of greater than 0.5, preferably at least 0.6, more preferably 0.7, still more preferably at least 0.8, even more preferably at least 0.9, and most preferably at least 0.95; an odds ratio different from 1, preferably at least about 2 or more or about 0.5 or less, more preferably at least about 3 or more or about 0.33 or less, still more preferably at least about 4 or more or about 0.25 or less, even more preferably at least about 5 or more or about 0.2 or less, and most preferably at least about 10 or more or about 0.1 or less; a positive likelihood ratio (calculated as sensitivity/(1−specificity)) of greater than 1, at least 2, more preferably at least 3, still more preferably at least 5, and most preferably at least 10; and or a negative likelihood ratio (calculated as (1-sensitivity)/specificity) of less than 1, less than or equal to 0.5, more preferably less than or equal to 0.3, and most preferably less than or equal to 0.1


Additional clinical indicia may be combined with the kidney injury marker assay result(s) of the present invention. These include other biomarkers related to renal status. Examples include the following, which recite the common biomarker name, followed by the Swiss-Prot entry number for that biomarker or its parent: Actin (P68133); Adenosine deaminase binding protein (DPP4, P27487); Alpha-1-acid glycoprotein 1 (P02763); Alpha-1-microglobulin (P02760); Albumin (P02768); Angiotensinogenase (Renin, P00797); Annexin A2 (P07355); Beta-glucuronidase (P08236); B-2-microglobulin (P61679); Beta-galactosidase (P16278); BMP-7 (P18075); Brain natriuretic peptide (proBNP, BNP-32, NTproBNP; P16860); Calcium-binding protein Beta (S100-beta, P04271); Carbonic anhydrase (Q16790); Casein Kinase 2 (P68400); Ceruloplasmin (P00450); Clusterin (P10909); Complement C3 (P01024); Cysteine-rich protein (CYR61, O00622); Cytochrome C(P99999); Epidermal growth factor (EGF, P01133); Endothelin-1 (P05305); Exosomal Fetuin-A (P02765); Fatty acid-binding protein, heart (FABP3, P05413); Fatty acid-binding protein, liver (P07148); Ferritin (light chain, P02793; heavy chain P02794); Fructose-1,6-biphosphatase (P09467); GRO-alpha (CXCL1, (P09341); Growth Hormone (P01241); Hepatocyte growth factor (P14210); Insulin-like growth factor I (P01343); Immunoglobulin G; Immunoglobulin Light Chains (Kappa and Lambda); Interferon gamma (P01308); Lysozyme (P61626); Interleukin-1alpha (P01583); Interleukin-2 (P60568); Interleukin-4 (P60568); Interleukin-9 (P15248); Interleukin-12p40 (P29460); Interleukin-13 (P35225); Interleukin-16 (Q14005); L1 cell adhesion molecule (P32004); Lactate dehydrogenase (P00338); Leucine Aminopeptidase (P28838); Meprin A-alpha subunit (Q16819); Meprin A-beta subunit (Q16820); Midkine (P21741); MIP2-alpha (CXCL2, P19875); MMP-2 (P08253); MMP-9 (P14780); Netrin-1 (O95631); Neutral endopeptidase (P08473); Osteopontin (P10451); Renal papillary antigen 1 (RPA1); Renal papillary antigen 2 (RPA2); Retinol binding protein (P09455); Ribonuclease; S100 calcium-binding protein A6 (P06703); Serum Amyloid P Component (P02743); Sodium/Hydrogen exchanger isoform (NHE3, P48764); Spermidine/spermine N1-acetyltransferase (P21673); TGF-Beta1 (P01137); Transferrin (P02787); Trefoil factor 3 (TFF3, Q07654); Toll-Like protein 4 (O00206); Total protein; Tubulointerstitial nephritis antigen (Q9UJW2); Uromodulin (Tamm-Horsfall protein, P07911).


For purposes of risk stratification, Adiponectin (Q15848); Alkaline phosphatase (P05186); Aminopeptidase N(P15144); CalbindinD28k (P05937); Cystatin C(P01034); 8 subunit of F1FO ATPase (P03928); Gamma-glutamyltransferase (P19440); GSTa (alpha-glutathione-S-transferase, P08263); GSTpi (Glutathione-S-transferase P; GST class-pi; P09211); IGFBP-1 (P08833); IGFBP-2 (P18065); IGFBP-6 (P24592); Integral membrane protein 1 (Itm1, P46977); Interleukin-6 (P05231); Interleukin-8 (P10145); Interleukin-18 (Q14116); IP-10 (10 kDa interferon-gamma-induced protein, P02778); IRPR (IFRD1, O00458); Isovaleryl-CoA dehydrogenase (IVD, P26440); I-TAC/CXCL11 (O14625); Keratin 19 (P08727); Kim-1 (Hepatitis A virus cellular receptor 1, O43656); L-arginine:glycine amidinotransferase (P50440); Leptin (P41159); Lipocalin2 (NGAL, P80188); MCP-1 (P13500); MIG (Gamma-interferon-induced monokine Q07325); MIP-1a (P10147); MIP-3a (P78556); MIP-1beta (P13236); MIP-1d (Q16663); NAG (N-acetyl-beta-D-glucosaminidase, P54802); Organic ion transporter (OCT2, O15244); Osteoprotegerin (O14788); P8 protein (O60356); Plasminogen activator inhibitor 1 (PAI-1, P05121); ProANP(1-98) (P01160); Protein phosphatase 1-beta (PPI-beta, P62140); Rab GDI-beta (P50395); Renal kallikrein (Q86U61); RT1.B-1 (alpha) chain of the integral membrane protein (Q5Y7A8); Soluble tumor necrosis factor receptor superfamily member 1A (sTNFR-I, P19438); Soluble tumor necrosis factor receptor superfamily member 1B (sTNFR-II, P20333); Tissue inhibitor of metalloproteinases 3 (TIMP-3, P35625); uPAR (Q03405) may be combined with the kidney injury marker assay result(s) of the present invention.


Other clinical indicia which may be combined with the kidney injury marker assay result(s) of the present invention includes demographic information (e.g., weight, sex, age, race), medical history (e.g., family history, type of surgery, pre-existing disease such as aneurism, congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, or sepsis, type of toxin exposure such as NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin), clinical variables (e.g., blood pressure, temperature, respiration rate), risk scores (APACHE score, PREDICT score, TIMI Risk Score for UA/NSTEMI, Framingham Risk Score), a urine total protein measurement, a glomerular filtration rate, an estimated glomerular filtration rate, a urine production rate, a serum or plasma creatinine concentration, a renal papillary antigen 1 (RPA1) measurement; a renal papillary antigen 2 (RPA2) measurement; a urine creatinine concentration, a fractional excretion of sodium, a urine sodium concentration, a urine creatinine to serum or plasma creatinine ratio, a urine specific gravity, a urine osmolality, a urine urea nitrogen to plasma urea nitrogen ratio, a plasma BUN to creatnine ratio, and/or a renal failure index calculated as urine sodium/(urine creatinine/plasma creatinine). Other measures of renal function which may be combined with the kidney injury marker assay result(s) are described hereinafter and in Harrison's Principles of Internal Medicine, 17th Ed., McGraw Hill, N.Y., pages 1741-1830, and Current Medical Diagnosis & Treatment 2008, 47th Ed, McGraw Hill, N.Y., pages 785-815, each of which are hereby incorporated by reference in their entirety.


Combining assay results/clinical indicia in this manner can comprise the use of multivariate logistical regression, loglinear modeling, neural network analysis, n-of-m analysis, decision tree analysis, etc. This list is not meant to be limiting.


Diagnosis of Acute Renal Failure


As noted above, the terms “acute renal (or kidney) injury” and “acute renal (or kidney) failure” as used herein are defined in part in terms of changes in serum creatinine from a baseline value. Most definitions of ARF have common elements, including the use of serum creatinine and, often, urine output. Patients may present with renal dysfunction without an available baseline measure of renal function for use in this comparison. In such an event, one may estimate a baseline serum creatinine value by assuming the patient initially had a normal GFR. Glomerular filtration rate (GFR) is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowman's capsule per unit time. Glomerular filtration rate (GFR) can be calculated by measuring any chemical that has a steady level in the blood, and is freely filtered but neither reabsorbed nor secreted by the kidneys. GFR is typically expressed in units of ml/min:






GFR
=


Urine





Concentration
×
Urine





Flow


Plasma





Concentration






By normalizing the GFR to the body surface area, a GFR of approximately 75-100 ml/min per 1.73 m2 can be assumed. The rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood.


There are several different techniques used to calculate or estimate the glomerular filtration rate (GFR or eGFR). In clinical practice, however, creatinine clearance is used to measure GFR. Creatinine is produced naturally by the body (creatinine is a metabolite of creatine, which is found in muscle). It is freely filtered by the glomerulus, but also actively secreted by the renal tubules in very small amounts such that creatinine clearance overestimates actual GFR by 10-20%. This margin of error is acceptable considering the ease with which creatinine clearance is measured.


Creatinine clearance (CCr) can be calculated if values for creatinine's urine concentration (UCr), urine flow rate (V), and creatinine's plasma concentration (PCr) are known. Since the product of urine concentration and urine flow rate yields creatinine's excretion rate, creatinine clearance is also said to be its excretion rate (UCr×V) divided by its plasma concentration. This is commonly represented mathematically as:







C
Cr

=



U
Cr

×
V


P
Cr






Commonly a 24 hour urine collection is undertaken, from empty-bladder one morning to the contents of the bladder the following morning, with a comparative blood test then taken:







C
Cr

=



U
Cr

×
24


-


hour





volume



P
Cr

×
24
×
60





mins






To allow comparison of results between people of different sizes, the CCr is often corrected for the body surface area (BSA) and expressed compared to the average sized man as ml/min/1.73 m2. While most adults have a BSA that approaches 1.7 (1.6-1.9), extremely obese or slim patients should have their CCr corrected for their actual BSA:







C

Cr
-
corrected


=



C

C
r


×
1.73

BSA





The accuracy of a creatinine clearance measurement (even when collection is complete) is limited because as glomerular filtration rate (GFR) falls creatinine secretion is increased, and thus the rise in serum creatinine is less. Thus, creatinine excretion is much greater than the filtered load, resulting in a potentially large overestimation of the GFR (as much as a twofold difference). However, for clinical purposes it is important to determine whether renal function is stable or getting worse or better. This is often determined by monitoring serum creatinine alone. Like creatinine clearance, the serum creatinine will not be an accurate reflection of GFR in the non-steady-state condition of ARF. Nonetheless, the degree to which serum creatinine changes from baseline will reflect the change in GFR. Serum creatinine is readily and easily measured and it is specific for renal function.


For purposes of determining urine output on a Urine output on a mL/kg/hr basis, hourly urine collection and measurement is adequate. In the case where, for example, only a cumulative 24-h output was available and no patient weights are provided, minor modifications of the RIFLE urine output criteria have been described. For example, Bagshaw et al., Nephrol. Dial. Transplant. 23: 1203-1210, 2008, assumes an average patient weight of 70 kg, and patients are assigned a RIFLE classification based on the following: <35 mL/h (Risk), <21 mL/h (Injury) or <4 mL/h (Failure).


Selecting a Treatment Regimen


Once a diagnosis is obtained, the clinician can readily select a treatment regimen that is compatible with the diagnosis, such as initiating renal replacement therapy, withdrawing delivery of compounds that are known to be damaging to the kidney, kidney transplantation, delaying or avoiding procedures that are known to be damaging to the kidney, modifying diuretic administration, initiating goal directed therapy, etc. The skilled artisan is aware of appropriate treatments for numerous diseases discussed in relation to the methods of diagnosis described herein. See, e.g., Merck Manual of Diagnosis and Therapy, 17th Ed. Merck Research Laboratories, Whitehouse Station, N.J., 1999. In addition, since the methods and compositions described herein provide prognostic information, the markers of the present invention may be used to monitor a course of treatment. For example, improved or worsened prognostic state may indicate that a particular treatment is or is not efficacious.


One skilled in the art readily appreciates that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. The examples provided herein are representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention.


Example 1
Contrast-Induced Nephropathy Sample Collection

The objective of this sample collection study is to collect samples of plasma and urine and clinical data from patients before and after receiving intravascular contrast media. Approximately 250 adults undergoing radiographic/angiographic procedures involving intravascular administration of iodinated contrast media are enrolled. To be enrolled in the study, each patient must meet all of the following inclusion criteria and none of the following exclusion criteria:


Inclusion Criteria

males and females 18 years of age or older;


undergoing a radiographic/angiographic procedure (such as a CT scan or coronary intervention) involving the intravascular administration of contrast media;


expected to be hospitalized for at least 48 hours after contrast administration.


able and willing to provide written informed consent for study participation and to comply with all study procedures.


Exclusion Criteria

renal transplant recipients;


acutely worsening renal function prior to the contrast procedure;


already receiving dialysis (either acute or chronic) or in imminent need of dialysis at enrollment;


expected to undergo a major surgical procedure (such as involving cardiopulmonary bypass) or an additional imaging procedure with contrast media with significant risk for further renal insult within the 48 hrs following contrast administration;


participation in an interventional clinical study with an experimental therapy within the previous 30 days;


known infection with human immunodeficiency virus (HIV) or a hepatitis virus.


Immediately prior to the first contrast administration (and after any pre-procedure hydration), an EDTA anti-coagulated blood sample (10 mL) and a urine sample (10 mL) are collected from each patient. Blood and urine samples are then collected at 4 (±0.5), 8 (±1), 24 (±2) 48 (±2), and 72 (±2) hrs following the last administration of contrast media during the index contrast procedure. Blood is collected via direct venipuncture or via other available venous access, such as an existing femoral sheath, central venous line, peripheral intravenous line or hep-lock. These study blood samples are processed to plasma at the clinical site, frozen and shipped to Astute Medical, Inc., San Diego, Calif. The study urine samples are frozen and shipped to Astute Medical, Inc.


Serum creatinine is assessed at the site immediately prior to the first contrast administration (after any pre-procedure hydration) and at 4 (±0.5), 8 (±1), 24 (±2) and 48 (±2)), and 72 (±2) hours following the last administration of contrast (ideally at the same time as the study samples are obtained). In addition, each patient's status is evaluated through day 30 with regard to additional serum and urine creatinine measurements, a need for dialysis, hospitalization status, and adverse clinical outcomes (including mortality).


Prior to contrast administration, each patient is assigned a risk based on the following assessment: systolic blood pressure<80 mm Hg=5 points; intra-arterial balloon pump=5 points; congestive heart failure (Class III-IV or history of pulmonary edema)=5 points; age>75 yrs=4 points; hematocrit level<39% for men, <35% for women=3 points; diabetes=3 points; contrast media volume=1 point for each 100 mL; serum creatinine level>1.5 g/dL=4 points OR estimated GFR 40-60 mL/min/1.73 m2=2 points, 20-40 mL/min/1.73 m2=4 points, <20 mL/min/1.73 m2=6 points. The risks assigned are as follows: risk for CIN and dialysis: 5 or less total points=risk of CIN—7.5%, risk of dialysis—0.04%; 6-10 total points=risk of CIN—14%, risk of dialysis—0.12%; 11-16 total points=risk of CIN—26.1%, risk of dialysis−1.09%; >16 total points=risk of CIN—57.3%, risk of dialysis—12.8%.


Example 2
Cardiac Surgery Sample Collection

The objective of this sample collection study is to collect samples of plasma and urine and clinical data from patients before and after undergoing cardiovascular surgery, a procedure known to be potentially damaging to kidney function. Approximately 900 adults undergoing such surgery are enrolled. To be enrolled in the study, each patient must meet all of the following inclusion criteria and none of the following exclusion criteria:


Inclusion Criteria

males and females 18 years of age or older;


undergoing cardiovascular surgery;


Toronto/Ottawa Predictive Risk Index for Renal Replacement risk score of at least 2 (Wijeysundera et al., JAMA 297: 1801-9, 2007); and


able and willing to provide written informed consent for study participation and to comply with all study procedures.


Exclusion Criteria

known pregnancy;


previous renal transplantation;


acutely worsening renal function prior to enrollment (e.g., any category of RIFLE criteria);


already receiving dialysis (either acute or chronic) or in imminent need of dialysis at enrollment;


currently enrolled in another clinical study or expected to be enrolled in another clinical study within 7 days of cardiac surgery that involves drug infusion or a therapeutic intervention for AKI;


known infection with human immunodeficiency virus (HIV) or a hepatitis virus.


Within 3 hours prior to the first incision (and after any pre-procedure hydration), an EDTA anti-coagulated blood sample (10 mL), whole blood (3 mL), and a urine sample (35 mL) are collected from each patient. Blood and urine samples are then collected at 3 (±0.5), 6 (±0.5), 12 (±1), 24 (±2) and 48 (±2) hrs following the procedure and then daily on days 3 through 7 if the subject remains in the hospital. Blood is collected via direct venipuncture or via other available venous access, such as an existing femoral sheath, central venous line, peripheral intravenous line or hep-lock. These study blood samples are frozen and shipped to Astute Medical, Inc., San Diego, Calif. The study urine samples are frozen and shipped to Astute Medical, Inc.


Example 3
Acutely Ill Subject Sample Collection

The objective of this study is to collect samples from acutely ill patients. Approximately 1900 adults expected to be in the ICU for at least 48 hours will be enrolled. To be enrolled in the study, each patient must meet all of the following inclusion criteria and none of the following exclusion criteria:


Inclusion Criteria

males and females 18 years of age or older;


Study population 1: approximately 300 patients that have at least one of:


shock (SBP<90 mmHg and/or need for vasopressor support to maintain MAP>60 mmHg and/or documented drop in SBP of at least 40 mmHg); and sepsis;


Study population 2: approximately 300 patients that have at least one of:


IV antibiotics ordered in computerized physician order entry (CPOE) within 24 hours of enrollment;


contrast media exposure within 24 hours of enrollment;


increased Intra-Abdominal Pressure with acute decompensated heart failure; and


severe trauma as the primary reason for ICU admission and likely to be hospitalized in the ICU for 48 hours after enrollment;


Study population 3: approximately 300 patients expected to be hospitalized through acute care setting (ICU or ED) with a known risk factor for acute renal injury (e.g. sepsis, hypotension/shock (Shock=systolic BP<90 mmHg and/or the need for vasopressor support to maintain a MAP>60 mmHg and/or a documented drop in SBP>40 mmHg), major trauma, hemorrhage, or major surgery); and/or expected to be hospitalized to the ICU for at least 24 hours after enrollment;


Study population 4: approximately 1000 patients that are 21 years of age or older, within 24 hours of being admitted into the ICU, expected to have an indwelling urinary catheter for at least 48 hours after enrollment, and have at least one of the following acute conditions within 24 hours prior to enrollment:


(i) respiratory SOFA score of ≧2 (PaO2/FiO2<300), (ii) cardiovascular SOFA score of ≧1 (MAP<70 mm Hg and/or any vasopressor required).


Exclusion Criteria

known pregnancy;


institutionalized individuals;


previous renal transplantation;


known acutely worsening renal function prior to enrollment (e.g., any category of RIFLE criteria);


received dialysis (either acute or chronic) within 5 days prior to enrollment or in imminent need of dialysis at the time of enrollment;


known infection with human immunodeficiency virus (HIV) or a hepatitis virus;


meets any of the following:


(i) active bleeding with an anticipated need for >4 units PRBC in a day;


(ii) hemoglobin<7 g/dL;


(iii) any other condition that in the physician's opinion would contraindicate drawing serial blood samples for clinical study purposes; meets only the SBP <90 mmHg inclusion criterion set forth above, and does not have shock in the attending physician's or principal investigator's opinion;


After obtaining informed consent, an EDTA anti-coagulated blood sample (10 mL) and a urine sample (25-50 mL) are collected from each patient. Blood and urine samples are then collected at 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), 36 (±2), 48 (±2), 60 (±2), 72 (±2), and 84 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. Blood is collected via direct venipuncture or via other available venous access, such as an existing femoral sheath, central venous line, peripheral intravenous line or hep-lock. These study blood samples are processed to plasma at the clinical site, frozen and shipped to Astute Medical, Inc., San Diego, Calif. The study urine samples are frozen and shipped to Astute Medical, Inc.


Example 4
Immunoassay Format

Analytes are measured using standard sandwich enzyme immunoassay techniques. A first antibody which binds the analyte is immobilized in wells of a 96 well polystyrene microplate. Analyte standards and test samples are pipetted into the appropriate wells and any analyte present is bound by the immobilized antibody. After washing away any unbound substances, a horseradish peroxidase-conjugated second antibody which binds the analyte is added to the wells, thereby forming sandwich complexes with the analyte (if present) and the first antibody. Following a wash to remove any unbound antibody-enzyme reagent, a substrate solution comprising tetramethylbenzidine and hydrogen peroxide is added to the wells. Color develops in proportion to the amount of analyte present in the sample. The color development is stopped and the intensity of the color is measured at 540 nm or 570 nm. An analyte concentration is assigned to the test sample by comparison to a standard curve determined from the analyte standards.


Units for the concentrations reported in the following data tables are as follows: Serum albumin—pg/mL, Protein S100-B—pg/mL, Glial cell line-derived neurotrophic factor—pg/mL, Resistin—pg/mL, Serum amyloid A protein—ng/mL, Hydrocortisone—ng/mL, Parathyroid hormone—pg/mL, and Tissue Plasminogen Activator—pg/mL. In the case of those kidney injury markers which are membrane proteins as described herein, the assays used in these examples detect soluble forms thereof.


Example 5
Apparently Healthy Donor and Chronic Disease Patient Samples

Human urine samples from donors with no known chronic or acute disease (“Apparently Healthy Donors”) were purchased from two vendors (Golden West Biologicals, Inc., 27625 Commerce Center Dr., Temecula, Calif. 92590 and Virginia Medical Research, Inc., 915 First Colonial Rd., Virginia Beach, Va. 23454). The urine samples were shipped and stored frozen at less than −20° C. The vendors supplied demographic information for the individual donors including gender, race (Black/White), smoking status and age.


Human urine samples from donors with various chronic diseases (“Chronic Disease Patients”) including congestive heart failure, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus and hypertension were purchased from Virginia Medical Research, Inc., 915 First Colonial Rd., Virginia Beach, Va. 23454. The urine samples were shipped and stored frozen at less than −20 degrees centigrade. The vendor provided a case report form for each individual donor with age, gender, race (Black/White), smoking status and alcohol use, height, weight, chronic disease(s) diagnosis, current medications and previous surgeries.


Example 6
Use of Kidney Injury Markers for Evaluating Renal Status in Patients

Patients from the intensive care unit (ICU) were enrolled in the following study. Each patient was classified by kidney status as non-injury (0), risk of injury (R), injury (I), and failure (F) according to the maximum stage reached within 7 days of enrollment as determined by the RIFLE criteria. EDTA anti-coagulated blood samples (10 mL) and a urine samples (25-30 mL) were collected from each patient at enrollment, 4 (±0.5) and 8 (±1) hours after contrast administration (if applicable); at 12 (±1), 24 (±2), and 48 (±2) hours after enrollment, and thereafter daily up to day 7 to day 14 while the subject is hospitalized. Markers were each measured by standard immunoassay methods using commercially available assay reagents in the urine samples and the plasma component of the blood samples collected.


Two cohorts were defined to represent a “diseased” and a “normal” population. While these terms are used for convenience, “diseased” and “normal” simply represent two cohorts for comparison (say RIFLE 0 vs RIFLE R, I and F; RIFLE 0 vs RIFLE R; RIFLE 0 and R vs RIFLE I and F; etc.). The time “prior max stage” represents the time at which a sample is collected, relative to the time a particular patient reaches the lowest disease stage as defined for that cohort, binned into three groups which are +/−12 hours. For example, “24 hr prior” which uses 0 vs R, I, F as the two cohorts would mean 24 hr (+/−12 hours) prior to reaching stage R (or I if no sample at R, or F if no sample at R or I).


A receiver operating characteristic (ROC) curve was generated for each biomarker measured and the area under each ROC curve (AUC) is determined Patients in Cohort 2 were also separated according to the reason for adjudication to cohort 2 as being based on serum creatinine measurements (sCr), being based on urine output (UO), or being based on either serum creatinine measurements or urine output. Using the same example discussed above (0 vs R, I, F), for those patients adjudicated to stage R, I, or F on the basis of serum creatinine measurements alone, the stage 0 cohort may include patients adjudicated to stage R, I, or F on the basis of urine output; for those patients adjudicated to stage R, I, or F on the basis of urine output alone, the stage 0 cohort may include patients adjudicated to stage R, I, or F on the basis of serum creatinine measurements; and for those patients adjudicated to stage R, I, or F on the basis of serum creatinine measurements or urine output, the stage 0 cohort contains only patients in stage 0 for both serum creatinine measurements and urine output. Also, in the data for patients adjudicated on the basis of serum creatinine measurements or urine output, the adjudication method which yielded the most severe RIFLE stage is used.


The ability to distinguish cohort 1 from Cohort 2 was determined using ROC analysis. SE is the standard error of the AUC, n is the number of sample or individual patients (“pts,” as indicated). Standard errors are calculated as described in Hanley, J. A., and McNeil, B. J., The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology (1982) 143: 29-36; p values are calculated with a two-tailed Z-test. An AUC <0.5 is indicative of a negative going marker for the comparison, and an AUC >0.5 is indicative of a positive going marker for the comparison.


Various threshold (or “cutoff”) concentrations were selected, and the associated sensitivity and specificity for distinguishing cohort 1 from cohort 2 are determined OR is the odds ratio calculated for the particular cutoff concentration, and 95% CI is the confidence interval for the odds ratio.









TABLE 1





Comparison of marker levels in urine samples collected from Cohort


1 (patients that did not progress beyond RIFLE stage 0) and in urine samples collected


from subjects at 0, 24 hours, and 48 hours prior to reaching stage R, I or F in Cohort 2.







Serum amyloid A protein














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
1.58
1.52
1.58
1.66
1.58
1.41


Average
85.0
79.1
85.0
190
85.0
4.77


Stdev
425
379
425
619
425
7.05


p(t-test)

0.91

0.17

0.51


Min
0.000420
0.000310
0.000420
0.000420
0.000420
0.000562


Max
2680
2680
2680
2680
2680
20.6


n (Samp)
150
92
150
58
150
12


n (Patient)
56
92
56
58
56
12














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
1.49
1.46
1.49
1.74
1.49
1.58


Average
67.4
11.1
67.4
109
67.4
227


Stdev
373
38.3
373
397
373
772


p(t-test)

0.45

0.62

0.16


Min
0.000420
0.0851
0.000420
0.452
0.000420
0.521


Max
2680
193
2680
1790
2680
2680


n (Samp)
412
25
412
20
412
12


n (Patient)
140
25
140
20
140
12














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
1.60
1.45
1.60
1.47
1.60
0.590


Average
73.1
83.9
73.1
155
73.1
2.34


Stdev
381
396
381
577
381
4.85


p(t-test)

0.83

0.20

0.52


Min
0.000420
0.000310
0.000420
0.000420
0.000420
0.000562


Max
2680
2680
2680
2680
2680
17.1


n (Samp)
208
84
208
59
208
12


n (Patient)
76
84
76
59
76
12













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.49
0.52
0.48
0.52
0.58


SE
0.038
0.060
0.038
0.045
0.068


P
0.86
0.71
0.51
0.69
0.26


nCohort 1
150
412
208
150
412


nCohort 2
92
25
84
58
20


Cutoff 1
0.945
1.18
0.906
1.08
1.25


Sens 1
71%
72%
70%
71%
70%


Spec 1
31%
41%
26%
35%
43%


Cutoff 2
0.701
1.06
0.612
0.853
0.945


Sens 2
80%
80%
81%
81%
80%


Spec 2
20%
36%
14%
25%
31%


Cutoff 3
0.249
0.794
0.249
0.435
0.641


Sens 3
90%
92%
90%
91%
90%


Spec 3
 3%
25%
 3%
 8%
19%


Cutoff 4
3.76
3.98
4.35
3.76
3.98


Sens 4
29%
24%
29%
33%
35%


Spec 4
70%
70%
70%
70%
70%


Cutoff 5
12.8
11.3
14.5
12.8
11.3


Sens 5
22%
12%
21%
19%
30%


Spec 5
80%
80%
80%
80%
80%


Cutoff 6
28.7
25.5
33.0
28.7
25.5


Sens 6
12%
 4%
12%
10%
20%


Spec 6
90%
90%
90%
90%
90%


OR Quart 2
0.83
3.6
1.0
1.5
1.0


p Value
0.62
0.059
1.0
0.38
1.0


95% CI of
0.40
0.95
0.48
0.62
0.24


OR Quart2
1.7
13
2.1
3.5
4.1


OR Quart 3
0.93
2.8
0.93
1.5
1.5


p Value
0.85
0.14
0.85
0.38
0.52


95% CI of
0.45
0.72
0.45
0.62
0.42


OR Quart3
1.9
11
1.9
3.5
5.6


OR Quart 4
1.0
1.3
1.4
1.2
1.5


p Value
0.94
0.71
0.37
0.65
0.52


95% CI of
0.50
0.29
0.68
0.50
0.42


OR Quart4
2.1
6.1
2.8
3.0
5.6















24 hr prior to





AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.47
0.41
0.52
0.25



SE
0.043
0.089
0.086
0.083



P
0.44
0.33
0.81
0.0030



nCohort 1
208
150
412
208



nCohort 2
59
12
12
12



Cutoff 1
0.950
0.371
0.873
0.314



Sens 1
71%
75%
75%
75%



Spec 1
29%
 6%
28%
 5%



Cutoff 2
0.619
0.314
0.853
0.278



Sens 2
81%
83%
83%
83%



Spec 2
15%
 5%
26%
 4%



Cutoff 3
0.371
0.000562
0.828
0.000562



Sens 3
92%
92%
92%
92%



Spec 3
 5%
 2%
25%
 1%



Cutoff 4
4.35
3.76
3.98
4.35



Sens 4
20%
33%
33%
17%



Spec 4
70%
70%
70%
70%



Cutoff 5
14.5
12.8
11.3
14.5



Sens 5
12%
17%
17%
 8%



Spec 5
80%
80%
80%
80%



Cutoff 6
33.0
28.7
25.5
33.0



Sens 6
 8%
 0%
 8%
 0%



Spec 6
90%
90%
90%
90%



OR Quart 2
1.7
1.0
2.0
2.0



p Value
0.21
0.97
0.42
0.57



95% CI of
0.74
0.19
0.37
0.18



OR Quart2
4.0
5.4
11
23



OR Quart 3
1.6
0.32
1.5
1.0



p Value
0.28
0.33
0.65
1.0



95% CI of
0.68
0.032
0.25
0.061



OR Quart3
3.8
3.2
9.3
16



OR Quart 4
1.5
1.8
1.5
9.2



p Value
0.36
0.44
0.65
0.040



95% CI of
0.63
0.40
0.25
1.1



OR Quart4
3.6
8.1
9.3
76










Tissue-type plasminogen activator














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
2.43
0.135
2.43
3.39
2.43
0.00535


Average
63.8
73.5
63.8
58.5
63.8
22.6


Stdev
351
501
351
215
351
50.2


p(t-test)

0.86

0.91

0.69


Min
0.00252
0.00252
0.00252
0.00314
0.00252
0.00314


Max
3940
4790
3940
1510
3940
132


n (Samp)
150
92
150
58
150
12


n (Patient)
56
92
56
58
56
12














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.176
0.00726
0.176
0.135
0.176
0.0348


Average
50.5
10.0
50.5
92.9
50.5
45.7


Stdev
320
28.1
320
335
320
154


p(t-test)

0.53

0.56

0.96


Min
0.00252
0.00252
0.00252
0.00453
0.00252
0.00297


Max
4790
117
4790
1510
4790
535


n (Samp)
412
25
412
20
412
12


n (Patient)
140
25
140
20
140
12














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
1.65
0.135
1.65
0.578
1.65
0.00503


Average
58.7
77.9
58.7
32.7
58.7
21.7


Stdev
316
524
316
92.4
316
50.6


p(t-test)

0.70

0.53

0.69


Min
0.00252
0.00252
0.00252
0.00297
0.00252
0.00252


Max
3940
4790
3940
535
3940
132


n (Samp)
208
84
208
59
208
12


n (Patient)
76
84
76
59
76
12













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.43
0.36
0.45
0.53
0.55


SE
0.038
0.061
0.038
0.045
0.068


P
0.079
0.026
0.20
0.45
0.42


nCohort 1
150
412
208
150
412


nCohort 2
92
25
84
58
20


Cutoff 1
0.00503
0.00453
0.00503
0.00726
0.00567


Sens 1
78%
72%
79%
76%
75%


Spec 1
19%
15%
22%
31%
30%


Cutoff 2
0.00453
0.00314
0.00453
0.00567
0.00564


Sens 2
83%
80%
83%
83%
90%


Spec 2
16%
10%
19%
28%
27%


Cutoff 3
0.00297
0
0.00297
0.00503
0.00564


Sens 3
90%
100% 
92%
93%
90%


Spec 3
 8%
 0%
11%
19%
27%


Cutoff 4
17.8
14.1
17.9
17.8
14.1


Sens 4
22%
12%
20%
31%
40%


Spec 4
70%
70%
70%
70%
70%


Cutoff 5
30.3
29.1
31.1
30.3
29.1


Sens 5
18%
 8%
18%
21%
25%


Spec 5
80%
80%
80%
80%
80%


Cutoff 6
72.2
70.3
76.5
72.2
70.3


Sens 6
11%
 8%
 8%
14%
10%


Spec 6
90%
90%
90%
90%
90%


OR Quart 2
1.0
1.4
1.5
2.2
4.8


p Value
0.95
0.69
0.33
0.080
0.048


95% CI of
0.48
0.30
0.68
0.91
1.0


OR Quart2
2.2
6.2
3.1
5.4
23


OR Quart 3
2.3
3.6
2.4
1.7
0.50


p Value
0.028
0.057
0.020
0.25
0.57


95% CI of
1.1
0.96
1.1
0.68
0.044


OR Quart3
4.8
13
5.0
4.2
5.5


OR Quart 4
1.4
2.8
1.6
1.7
4.2


p Value
0.41
0.13
0.25
0.25
0.072


95% CI of
0.65
0.73
0.73
0.68
0.88


OR Quart4
2.9
11
3.3
4.2
20















24 hr prior





to AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.53
0.38
0.37
0.33



SE
0.043
0.089
0.088
0.088



P
0.45
0.17
0.13
0.051



nCohort 1
208
150
412
208



nCohort 2
59
12
12
12



Cutoff 1
0.00726
0.00314
0.00297
0.00314



Sens 1
76%
92%
92%
75%



Spec 1
36%
11%
 6%
13%



Cutoff 2
0.00567
0.00314
0.00297
0.00297



Sens 2
81%
92%
92%
83%



Spec 2
30%
11%
 6%
11%



Cutoff 3
0.00503
0.00314
0.00297
0.00252



Sens 3
93%
92%
92%
92%



Spec 3
22%
11%
 6%
 5%



Cutoff 4
17.9
17.8
14.1
17.9



Sens 4
27%
17%
 8%
17%



Spec 4
70%
70%
70%
70%



Cutoff 5
31.1
30.3
29.1
31.1



Sens 5
17%
17%
 8%
17%



Spec 5
80%
80%
80%
80%



Cutoff 6
76.5
72.2
70.3
76.5



Sens 6
14%
17%
 8%
17%



Spec 6
90%
90%
90%
90%



OR Quart 2
2.6
1.0
4.1
0



p Value
0.030
0.98
0.21
na



95% CI of
1.1
0.14
0.45
na



OR Quart2
6.0
7.7
37
na



OR Quart 3
1.5
1.0
2.0
1.5



p Value
0.39
1.0
0.57
0.65



95% CI of
0.60
0.13
0.18
0.25



OR Quart3
3.6
7.5
23
9.5



OR Quart 4
1.5
3.4
5.2
3.9



p Value
0.39
0.15
0.14
0.10



95% CI of
0.60
0.65
0.60
0.77



OR Quart4
3.6
18
45
20










Glial cell line-derived neurotrophic factor














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.00569
0.200
0.00569
0.200
0.00569
0.422


Average
0.218
0.256
0.218
1.61
0.218
0.343


Stdev
0.373
0.284
0.373
6.02
0.373
0.308


p(t-test)

0.69

0.088

0.57


Min
0.00388
0.00388
0.00388
0.00388
0.00388
0.00388


Max
2.07
1.01
2.07
26.5
2.07
0.604


n (Samp)
55
18
55
19
55
3


n (Patient)
44
18
44
19
44
3














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.200
0.148
0.200
0.200
0.200
0.213


Average
0.513
0.192
0.513
0.202
0.513
0.213


Stdev
2.71
0.246
2.71
0.245
2.71
0.296


p(t-test)

0.79

0.80

0.88


Min
0.00388
0.00388
0.00388
0.00388
0.00388
0.00388


Max
26.5
0.604
26.5
0.604
26.5
0.422


n (Samp)
95
5
95
5
95
2


n (Patient)
76
5
76
5
76
2














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.00569
0.200
0.00569
0.200
0.00569
0.00388


Average
0.228
0.262
0.228
1.51
0.228
0.153


Stdev
0.366
0.300
0.366
5.88
0.366
0.260


p(t-test)

0.76

0.14

0.66


Min
0.00388
0.00388
0.00388
0.00388
0.00388
0.00388


Max
2.07
1.01
2.07
26.5
2.07
0.604


n (Samp)
47
14
47
20
47
5


n (Patient)
37
14
37
20
37
5













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.60
0.46
0.57
0.62
0.48


SE
0.080
0.14
0.090
0.078
0.13


P
0.21
0.74
0.45
0.14
0.88


nCohort 1
55
95
47
55
95


nCohort 2
18
5
14
19
5


Cutoff 1
0.00388
0
0.00388
0.00777
0


Sens 1
78%
100% 
79%
79%
100% 


Spec 1
40%
 0%
30%
60%
 0%


Cutoff 2
0
0
0
0
0


Sens 2
100% 
100% 
100% 
100% 
100% 


Spec 2
 0%
 0%
 0%
 0%
 0%


Cutoff 3
0
0
0
0
0


Sens 3
100% 
100% 
100% 
100% 
100% 


Spec 3
 0%
 0%
 0%
 0%
 0%


Cutoff 4
0.200
0.200
0.402
0.200
0.200


Sens 4
28%
20%
29%
32%
20%


Spec 4
71%
71%
72%
71%
71%


Cutoff 5
0.422
0.422
0.422
0.422
0.422


Sens 5
22%
20%
21%
16%
20%


Spec 5
87%
84%
87%
87%
84%


Cutoff 6
0.604
0.604
0.604
0.604
0.604


Sens 6
 6%
 0%
 7%
 5%
 0%


Spec 6
93%
92%
96%
93%
92%


OR Quart 2
1.0
1.0
0.62
0.94
2.1


p Value
1.0
1.0
0.63
0.95
0.56


95% CI of
0.17
0.059
0.087
0.12
0.18


OR Quart2
5.8
17
4.3
7.5
25


OR Quart 3
3.2
1.0
2.0
13
1.0


p Value
0.15
1.0
0.41
0.0046
1.0


95% CI of
0.67
0.059
0.38
2.2
0.059


OR Quart3
15
17
11
72
17


OR Quart 4
1.8
2.1
1.3
2.1
1.0


p Value
0.48
0.56
0.74
0.42
1.0


95% CI of
0.36
0.18
0.24
0.34
0.059


OR Quart4
8.9
25
7.3
13
17

















24 hr prior to















AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.53
0.63
0.47
0.38



SE
0.078
0.18
0.21
0.14



P
0.70
0.45
0.89
0.40



nCohort 1
47
55
95
47



nCohort 2
20
3
2
5



Cutoff 1
0.00388
0
0
0



Sens 1
70%
100% 
100% 
100% 



Spec 1
30%
 0%
 0%
 0%



Cutoff 2
0
0
0
0



Sens 2
100% 
100% 
100% 
100% 



Spec 2
 0%
 0%
 0%
 0%



Cutoff 3
0
0
0
0



Sens 3
100% 
100% 
100% 
100% 



Spec 3
 0%
 0%
 0%
 0%



Cutoff 4
0.402
0.200
0.200
0.402



Sens 4
25%
67%
50%
20%



Spec 4
72%
71%
71%
72%



Cutoff 5
0.422
0.422
0.422
0.422



Sens 5
15%
33%
 0%
20%



Spec 5
87%
87%
84%
87%



Cutoff 6
0.604
0.604
0.604
0.604



Sens 6
 5%
 0%
 0%
 0%



Spec 6
96%
93%
92%
96%



OR Quart 2
0.29 
0
0
1.0



p Value
0.19 
na
na
1.0



95% CI of
0.048
na
na
0.056



OR Quart2
1.8 
na
na
18



OR Quart 3
2.5 
1.0
0
1.0



p Value
0.21 
1.0
na
1.0



95% CI of
0.60 
0.056
na
0.056



OR Quart3
10   
18
na
18



OR Quart 4
0.68 
0.93
1.0
2.2



p Value
0.62 
0.96
0.98
0.55



95% CI of
0.15 
0.053
0.062
0.17



OR Quart4
3.2 
16
18
28










Protein S100-B














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.0871
3.15
0.0871
6.21
0.0871
0.755


Average
6.52
16.5
6.52
81.9
6.52
2.34


Stdev
15.5
28.0
15.5
283
15.5
3.37


p(t-test)

0.059

0.050

0.65


Min
0.0517
0.0517
0.0517
0.0517
0.0517
0.0517


Max
79.8
105
79.8
1240
79.8
6.21


n (Samp)
55
18
55
19
55
3


n (Patient)
44
18
44
19
44
3














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.0871
21.8
0.0871
26.8
0.0871
4.98


Average
20.4
36.6
20.4
36.6
20.4
4.98


Stdev
128
40.2
128
32.9
128
1.75


p(t-test)

0.78

0.78

0.87


Min
0.0517
0.0517
0.0517
0.0517
0.0517
3.74


Max
1240
105
1240
88.3
1240
6.21


n (Samp)
95
5
95
5
95
2


n (Patient)
76
5
76
5
76
2














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.0871
0.0871
0.0871
6.21
0.0871
20.7


Average
8.94
10.8
8.94
78.1
8.94
30.3


Stdev
20.3
19.1
20.3
276
20.3
43.2


p(t-test)

0.77

0.089

0.053


Min
0.0517
0.0517
0.0517
0.0517
0.0517
0.0517


Max
88.3
57.4
88.3
1240
88.3
105


n (Samp)
47
14
47
20
47
5


n (Patient)
37
14
37
20
37
5













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.54
0.77
0.50
0.64
0.78


SE
0.080
0.13
0.089
0.077
0.12


P
0.63
0.031
0.96
0.072
0.022


nCohort 1
55
95
47
55
95


nCohort 2
18
5
14
19
5


Cutoff 1
0
19.5
0
0
22.9


Sens 1
100% 
80%
100% 
100% 
80%


Spec 1
 0%
88%
 0%
 0%
89%


Cutoff 2
0
19.5
0
0
22.9


Sens 2
100% 
80%
100% 
100% 
80%


Spec 2
 0%
88%
 0%
 0%
89%


Cutoff 3
0
0
0
0
0


Sens 3
100% 
100% 
100% 
100% 
100% 


 Spec 3
 0%
 0%
 0%
 0%
 0%


Cutoff 4
1.55
6.21
1.55
1.55
6.21


Sens 4
50%
80%
43%
63%
80%


Spec 4
73%
73%
70%
73%
73%


Cutoff 5
10.3
12.4
10.3
10.3
12.4


Sens 5
33%
80%
21%
47%
80%


Spec 5
82%
81%
81%
82%
81%


Cutoff 6
23.8
23.8
26.8
23.8
23.8


Sens 6
17%
40%
14%
26%
60%


Spec 6
93%
92%
91%
93%
92%


OR Quart 2
0.40
0
0.46
0.41
0


p Value
0.26
na
0.42
0.34
na


95% CI of
0.082
na
0.071
0.065
na


OR Quart2
1.9
na
3.0
2.6
na


OR Quart 3
0.40
0
2.6
1.0
0


p Value
0.26
na
0.21
1.0
na


95% CI of
0.082
na
0.57
0.21
na


OR Quart3
1.9
na
12
4.8
na


OR Quart 4
0.92
4.6
0.21
3.1
4.6


p Value
0.91
0.19
0.19
0.12
0.19


95% CI of
0.23
0.47
0.021
0.75
0.47


OR Quart4
3.7
44
2.2
13
44

















24 hr prior to















AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.62
0.52
0.69
0.71



SE
0.077
0.17
0.21
0.14



P
0.11
0.90
0.38
0.12



nCohort 1
47
55
95
47



nCohort 2
20
3
2
5



Cutoff 1
0.0871
0
1.55
0.0871



Sens 1
70%
100% 
100% 
80%



Spec 1
62%
 0%
67%
62%



Cutoff 2
0
0
1.55
0.0871



Sens 2
100% 
100% 
100% 
80%



Spec 2
 0%
 0%
67%
62%



Cutoff 3
0
0
1.55
0



Sens 3
100% 
100% 
100% 
100% 



 Spec 3
 0%
 0%
67%
 0%



Cutoff 4
1.55
1.55
6.21
1.55



Sens 4
60%
33%
 0%
60%



Spec 4
70%
73%
73%
70%



Cutoff 5
10.3
10.3
12.4
10.3



Sens 5
40%
 0%
 0%
60%



Spec 5
81%
82%
81%
81%



Cutoff 6
26.8
23.8
23.8
26.8



Sens 6
20%
 0%
 0%
20%



Spec 6
91%
93%
92%
91%



OR Quart 2
2.2
0
>0
>1.1



p Value
0.42
na
<na  
<0.96



95% CI of
0.34
na
>na  
>0.061



OR Quart2
14
na
na
na



OR Quart 3
3.8
1.0
>2.2
>1.1



p Value
0.14
1.0
<0.54
<0.96



95% CI of
0.64
0.056
>0.18
>0.061



OR Quart3
23
18
na
na



OR Quart 4
6.2
0.93
>0
>3.9



p Value
0.042
0.96
<na  
<0.27



95% CI of
1.1
0.053
>na  
>0.35



OR Quart4
36
16
na
na










Resistin














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
44800
44300
44800
42900
44800
50500


Average
48600
51700
48600
51100
48600
50300


Stdev
25700
24400
25700
27500
25700
24600


p(t-test)

0.15

0.36

0.76


Min
2250
6850
2250
1230
2250
11800


Max
116000
125000
116000
100000
116000
104000


n (Samp)
464
194
464
117
464
25


n (Patient)
180
194
180
117
180
25














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
45200
43500
45200
45900
45200
61600


Average
50100
51300
50100
51800
50100
60600


Stdev
25200
24300
25200
28300
25200
22500


p(t-test)

0.72

0.66

0.027


Min
863
9330
863
1230
863
22300


Max
150000
100000
150000
101000
150000
100000


n (Samp)
1177
61
1177
49
1177
29


n (Patient)
369
61
369
49
369
29














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
43800
45700
43800
43500
43800
43300


Average
48400
51900
48400
52200
48400
48900


Stdev
25900
23700
25900
26500
25900
26100


p(t-test)

0.10

0.15

0.92


Min
1230
6850
1230
6450
1230
11800


Max
118000
125000
118000
100000
118000
104000


n (Samp)
575
179
575
117
575
28


n (Patient)
207
179
207
117
207
28













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.53
0.51
0.54
0.51
0.52


SE
0.025
0.038
0.025
0.030
0.042


P
0.20
0.71
0.077
0.66
0.70


nCohort 1
464
1177
575
464
1177


nCohort 2
194
61
179
117
49


Cutoff 1
37200
38900
37200
33500
38200


Sens 1
70%
70%
70%
70%
71%


Spec 1
37%
38%
38%
31%
36%


Cutoff 2
33200
33600
33900
28700
28700


Sens 2
80%
80%
80%
80%
82%


Spec 2
30%
27%
33%
21%
18%


Cutoff 3
27400
24400
27800
23000
15000


Sens 3
90%
90%
91%
91%
92%


Spec 3
20%
13%
21%
15%
 5%


Cutoff 4
57600
58400
58100
57600
58400


Sens 4
28%
30%
29%
36%
29%


Spec 4
70%
70%
70%
70%
70%


Cutoff 5
66300
69600
66800
66300
69600


Sens 5
24%
21%
23%
26%
22%


Spec 5
80%
80%
80%
80%
80%


Cutoff 6
100000
97900
100000
100000
97900


Sens 6
 1%
11%
 1%
 0%
18%


Spec 6
99%
90%
99%
99%
90%


OR Quart 2
2.4
1.9
2.5
1.4
0.91


p Value
4.1E−4
0.10
4.9E−4
0.25
0.83


95% CI of
1.5
0.88
1.5
0.79
0.40


OR QuaA2
4.0
4.0
4.1
2.4
2.1


OR Quart 3
1.4
1.4
1.9
0.74
1.1


p Value
0.16
0.42
0.015
0.34
0.84


95% CI of
0.87
0.62
1.1
0.40
0.49


OR Quart3
2.4
3.1
3.2
1.4
2.4


OR Quart 4
1.7
1.4
1.9
1.3
1.1


p Value
0.036
0.43
0.016
0.33
0.84


95% CI of
1.0
0.62
1.1
0.75
0.49


OR Quart4
2.8
3.0
3.2
2.3
2.4







24 hr prior















to AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.53
0.53
0.64
0.50



SE
0.030
0.060
0.056
0.056



P
0.25
0.63
0.016
0.98



nCohort 1
575
464
1177
575



nCohort 2
117
25
29
28



Cutoff 1
34300
34800
48700
33200



Sens 1
70%
72%
72%
71%



Spec 1
33%
33%
56%
31%



Cutoff 2
31600
29900
35000
24300



Sens 2
80%
80%
83%
82%



Spec 2
28%
23%
30%
16%



Cutoff 3
24700
21800
26200
21800



Sens 3
91%
92%
93%
93%



Spec 3
17%
13%
15%
14%



Cutoff 4
58100
57600
58400
58100



Sens 4
36%
36%
59%
25%



Spec 4
70%
70%
70%
70%



Cutoff 5
66800
66300
69600
66800



Sens 5
26%
24%
38%
21%



Spec 5
80%
80%
80%
80%



Cutoff 6
100000
100000
97900
100000



Sens 6
 0%
 4%
 7%
 4%



Spec 6
99%
99%
90%
99%



OR Quart 2
1.9
1.0
0.74
1.1



p Value
0.025
1.0
0.70
0.80



95% CI of
1.1
0.31
0.17
0.40



OR QuaA2
3.4
3.2
3.4
3.2



OR Quart 3
1.1
0.83
2.3
0.85



p Value
0.87
0.76
0.17
0.77



95% CI of
0.56
0.25
0.70
0.28



OR Quart3
2.0
2.8
7.5
2.6



OR Quart 4
1.7
1.3
3.3
0.99



p Value
0.082
0.59
0.037
0.99



95% CI of
0.94
0.45
1.1
0.34



OR Quart4
3.0
4.0
10
2.9










Parathyroid hormone














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
14.7
17.2
14.7
17.2
14.7
6.12


Average
20.2
24.3
20.2
23.6
20.2
14.8


Stdev
22.6
31.0
22.6
22.3
22.6
29.8


p(t-test)

0.041

0.094

0.12


Min
0.000320
0.000439
0.000320
0.00103
0.000320
0.00935


Max
302
268
302
106
302
191


n (Samp)
535
231
535
158
535
51


n (Patient)
211
231
211
158
211
51














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
16.0
17.7
16.0
14.1
16.0
9.56


Average
22.2
24.9
22.2
21.4
22.2
19.2


Stdev
26.9
25.8
26.9
21.3
26.9
31.1


p(t-test)

0.38

0.82

0.49


Min
0.000320
0.0209
0.000320
0.00185
0.000320
0.00935


Max
433
141
433
80.1
433
191


n (Samp)
1415
74
1415
66
1415
41


n (Patient)
452
74
452
66
452
41














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
15.4
16.4
15.4
17.2
15.4
8.25


Average
21.8
23.5
21.8
22.6
21.8
15.4


Stdev
23.5
31.2
23.5
21.4
23.5
19.0


p(t-test)

0.39

0.69

0.065


Min
0.000320
0.000439
0.000320
0.00103
0.000320
0.0392


Max
302
268
302
106
302
90.6


n (Samp)
661
218
661
149
661
49


n (Patient)
242
218
242
149
242
49













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.54
0.53
0.51
0.54
0.48


SE
0.023
0.035
0.023
0.026
0.037


P
0.074
0.37
0.82
0.18
0.65


nCohort 1
535
1415
661
535
1415


nCohort 2
231
74
218
158
66


Cutoff 1
9.21
8.48
8.40
7.50
6.06


Sens 1
70%
70%
70%
70%
71%


Spec 1
36%
31%
31%
31%
22%


Cutoff 2
6.13
5.84
5.94
4.08
3.39


Sens 2
80%
81%
80%
80%
80%


Spec 2
25%
22%
22%
17%
13%


Cutoff 3
3.78
3.75
2.67
0.930
1.04


Sens 3
90%
91%
90%
91%
91%


Spec 3
17%
14%
11%
 6%
 6%


Cutoff 4
24.5
24.8
25.8
24.5
24.8


Sens 4
32%
38%
27%
38%
32%


Spec 4
70%
70%
70%
70%
70%


Cutoff 5
30.7
32.2
33.9
30.7
32.2


Sens 5
20%
24%
17%
30%
26%


Spec 5
80%
80%
80%
80%
80%


Cutoff 6
43.3
47.5
47.0
43.3
47.5


Sens 6
12%
18%
10%
18%
14%


Spec 6
90%
90%
90%
90%
90%


OR Quart 2
1.2
0.74
1.2
0.47
0.51


p Value
0.51
0.39
0.39
0.0075
0.095


95% CI of
0.74
0.37
0.78
0.27
0.24


OR Quart2
1.8
1.5
1.9
0.82
1.1


OR Quart 3
1.4
0.79
1.2
0.85
0.84


p Value
0.18
0.50
0.33
0.53
0.61


95% CI of
0.87
0.40
0.80
0.52
0.42


OR Quart3
2.1
1.6
1.9
1.4
1.7


OR Quart 4
1.4
1.2
1.0
1.2
1.1


p Value
0.16
0.64
0.93
0.42
0.74


95% CI of
0.89
0.62
0.65
0.76
0.59


OR Quart4
2.1
2.1
1.6
2.0
2.1







24 hr prior















to AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.51
0.33
0.42
0.38



SE
0.026
0.043
0.047
0.044



P
0.74
9.9E−5
0.078
0.0046



nCohort 1
661
535
1415
661



nCohort 2
149
51
41
49



Cutoff 1
7.41
1.43
4.93
1.65



Sens 1
70%
71%
71%
71%



Spec 1
29%
 8%
19%
 7%



Cutoff 2
4.46
0.885
2.63
1.04



Sens 2
81%
80%
80%
82%



Spec 2
17%
 6%
11%
 5%



Cutoff 3
0.930
0.427
0.996
0.498



Sens 3
91%
90%
90%
92%



Spec 3
 4%
 3%
 6%
 3%



Cutoff 4
25.8
24.5
24.8
25.8



Sens 4
37%
12%
24%
20%



Spec 4
70%
70%
70%
70%



Cutoff 5
33.9
30.7
32.2
33.9



Sens 5
20%
12%
17%
14%



Spec 5
80%
80%
80%
80%



Cutoff 6
47.0
43.3
47.5
47.0



Sens 6
15%
 6%
 7%
 6%



Spec 6
90%
90%
90%
90%



OR Quart 2
0.50
1.7
1.4
1.0



p Value
0.011
0.30
0.46
0.99



95% CI of
0.29
0.61
0.54
0.41



OR Quart2
0.85
4.9
3.8
2.5



OR Quart 3
0.86
1.7
1.0
0.69



p Value
0.53
0.31
1.0
0.46



95% CI of
0.53
0.61
0.35
0.26



OR Quart3
1.4
4.8
2.9
1.8



OR Quart 4
1.0
4.9
2.5
2.4



p Value
0.92
8.0E−4
0.044
0.029



95% CI of
0.64
1.9
1.0
1.1



OR Quart4
1.6
12
6.1
5.2










Serum albumin














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
17800
36700
17800
38700
17800
16900


Average
52800
77800
52800
69200
52800
41300


Stdev
151000
122000
151000
131000
151000
45800


p(t-test)

0.043

0.28

0.70


Min
0.846
1.68
0.846
1.78
0.846
1.68


Max
1650000
1280000
1650000
1280000
1650000
181000


n (Samp)
462
192
462
115
462
25


n (Patient)
179
192
179
115
179
25














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
28200
27400
28200
45900
28200
31700


Average
74200
70500
74200
82800
74200
89600


Stdev
170000
87900
170000
103000
170000
200000


p(t-test)

0.87

0.73

0.63


Min
0.846
831
0.846
1.78
0.846
1.10


Max
1780000
380000
1780000
495000
1780000
1070000


n (Samp)
1165
62
1165
48
1165
29


n (Patient)
367
62
367
48
367
29














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
18700
39400
18700
38400
18700
35600


Average
52300
79700
52300
69400
52300
74800


Stdev
139000
125000
139000
132000
139000
175000


p(t-test)

0.020

0.22

0.40


Min
0.846
1.68
0.846
1750
0.846
1.68


Max
1650000
1280000
1650000
1280000
1650000
958000


n (Samp)
570
176
570
115
570
29


n (Patient)
206
176
206
115
206
29













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.64
0.55
0.65
0.61
0.56


SE
0.025
0.038
0.025
0.030
0.044


P
7.8E−9
0.22
1.9E−9
1.9E−4
0.16


nCohort 1
462
1165
570
462
1165


nCohort 2
192
62
176
115
48


Cutoff 1
18500
15400
20700
13400
13500


Sens 1
70%
71%
70%
70%
71%


Spec 1
51%
36%
53%
40%
32%


Cutoff 2
10600
10300
12000
8450
9100


Sens 2
80%
81%
80%
80%
81%


Spec 2
35%
26%
38%
28%
23%


Cutoff 3
5770
6470
6460
4690
2800


Sens 3
90%
90%
90%
90%
92%


Spec 3
21%
17%
22%
17%
9%


Cutoff 4
37500
55400
38200
37500
55400


Sens 4
48%
39%
51%
51%
42%


Spec 4
70%
70%
70%
70%
70%


Cutoff 5
55400
83700
62600
55400
83700


Sens 5
37%
26%
34%
40%
35%


Spec 5
80%
80%
80%
80%
80%


Cutoff 6
91500
149000
101000
91500
149000


Sens 6
25%
16%
23%
21%
21%


Spec 6
90%
90%
90%
90%
90%


OR Quart 2
1.6
2.3
1.5
0.95
1.1


p Value
0.085
0.034
0.16
0.87
0.82


95% CI of
0.94
1.1
0.85
0.50
0.46


OR Quart2
2.8
4.9
2.6
1.8
2.6


OR Quart 3
2.3
1.1
2.8
1.0
1.0


p Value
0.0023
0.83
1.9E−4
1.0
1.0


95% CI of
1.3
0.46
1.6
0.53
0.41


OR Quart3
3.8
2.6
4.7
1.9
2.4


OR Quart 4
3.7
2.0
3.5
2.5
1.7


p Value
5.8E−7
0.094
2.7E−6
0.0013
0.18


95% CI of
2.2
0.89
2.1
1.4
0.78


OR Quart4
6.1
4.3
5.9
4.4
3.9







24 hr prior















to AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.62
0.55
0.53
0.59



SE
0.030
0.061
0.055
0.057



P
9.7E−5
0.38
0.58
0.13



nCohort 1
570
462
1165
570



nCohort 2
115
25
29
29



Cutoff 1
14200
12600
12400
14000



Sens 1
70%
72%
72%
72%



Spec 1
42%
39%
30%
42%



Cutoff 2
10400
9880
9110
9880



Sens 2
80%
80%
83%
83%



Spec 2
34%
34%
23%
33%



Cutoff 3
5340
5110
5110
6460



Sens 3
90%
92%
93%
93%



Spec 3
20%
19%
15%
22%



Cutoff 4
38200
37500
55400
38200



Sens 4
50%
40%
34%
45%



Spec 4
70%
70%
70%
70%



Cutoff 5
62600
55400
83700
62600



Sens 5
35%
24%
31%
28%



Spec 5
80%
80%
80%
80%



Cutoff 6
101000
91500
149000
101000



Sens 6
16%
16%
10%
14%



Spec 6
90%
90%
90%
90%



OR Quart 2
1.3
2.3
1.3
1.8



p Value
0.42
0.17
0.59
0.29



95% CI of
0.69
0.70
0.46
0.60



OR Quart2
2.5
7.8
3.9
5.6



OR Quart 3
1.4
0.99
1.0
0.99



p Value
0.26
0.99
1.0
0.99



95% CI of
0.76
0.24
0.32
0.28



OR Quart3
2.7
4.1
3.1
3.5



OR Quart 4
2.9
2.1
1.5
2.1



p Value
3.2E−4
0.25
0.44
0.20



95% CI of
1.6
0.60
0.53
0.69



OR Quart4
5.2
7.0
4.3
6.2










Cortisol














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr or UO
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
137
179
137
158
137
117


Average
254
342
254
291
254
264


Stdev
305
370
305
324
305
336


p(t-test)

1.2E−4

0.13

0.79


Min
1.43
2.67
1.43
0.000854
1.43
3.78


Max
1500
1500
1500
1500
1500
1500


n (Samp)
757
271
757
204
757
66


n (Patient)
339
271
339
204
339
66














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













sCr only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
162
144
162
96.8
162
140


Average
293
292
293
210
293
249


Stdev
331
387
331
239
331
297


p(t-test)

0.99

0.026

0.36


Min
1.42
2.67
1.42
0.000854
1.42
3.78


Max
1500
1500
1500
1000
1500
1270


n (Samp)
1783
90
1783
81
1783
50


n (Patient)
608
90
608
81
608
50














0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage













UO only
Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
132
202
132
174
132
115


Average
253
377
253
333
253
279


Stdev
309
372
309
367
309
364


p(t-test)

1.3E−7

0.0018

0.52


Min
1.43
20.0
1.43
7.98
1.43
7.81


Max
1500
1500
1500
1500
1500
1500


n (Samp)
833
252
833
194
833
64


n (Patient)
316
252
316
194
316
64













0 hr prior to AKI stage
24 hr prior to AKI stage













sCr or UO
sCr only
UO only
sCr or UO
sCr only





AUC
0.58
0.45
0.62
0.54
0.41


SE
0.021
0.032
0.021
0.023
0.034


P
1.1E−4
0.16
3.2E−9
0.085
0.0071


nCohort 1
757
1783
833
757
1783


nCohort 2
271
90
252
204
81


Cutoff 1
98.1
59.1
116
90.6
62.5


Sens 1
70%
70%
70%
70%
70%


Spec 1
36%
18%
45%
34%
20%


Cutoff 2
73.2
47.3
82.3
59.1
46.8


Sens 2
80%
80%
80%
80%
80%


Spec 2
28%
13%
32%
23%
13%


Cutoff 3
53.3
29.8
60.3
35.9
27.8


Sens 3
90%
90%
90%
90%
90%


Spec 3
20%
 8%
25%
14%
 7%


Cutoff 4
239
295
239
239
295


Sens 4
39%
23%
44%
37%
26%


Spec 4
70%
70%
70%
70%
70%


Cutoff 5
363
464
360
363
464


Sens 5
31%
18%
36%
25%
12%


Spec 5
80%
80%
80%
80%
80%


Cutoff 6
732
805
725
732
805


Sens 6
15%
13%
18%
12%
 4%


Spec 6
90%
90%
90%
90%
90%


OR Quart 2
1.4
0.85
1.9
0.81
0.82


p Value
0.12
0.63
0.0059
0.35
0.58


95% CI of
0.92
0.45
1.2
0.51
0.40


OR Quart2
2.1
1.6
2.9
1.3
1.7


OR Quart 3
1.3
0.95
1.8
1.1
1.1


p Value
0.21
0.88
0.014
0.82
0.86


95% CI of
0.86
0.51
1.1
0.68
0.54


OR Quart3
2.0
1.8
2.8
1.6
2.1


OR Quart 4
2.1
1.5
3.3
1.3
1.9


p Value
4.1E−4
0.15
3.2E−8
0.29
0.030


95% CI of
1.4
0.86
2.2
0.82
1.1


OR Quart4
3.1
2.7
5.1
1.9
3.6







24 hr prior















to AKI stage
48 hr prior to AKI stage














UO only
sCr or UO
sCr only
UO only






AUC
0.58
0.48
0.45
0.48



SE
0.023
0.037
0.042
0.038



P
0.0011
0.68
0.24
0.67



nCohort 1
833
757
1783
833



nCohort 2
194
66
50
64



Cutoff 1
103
66.3
79.6
58.1



Sens 1
70%
71%
70%
70%



Spec 1
41%
25%
26%
24%



Cutoff 2
63.4
54.0
45.7
48.1



Sens 2
80%
80%
80%
81%



Spec 2
26%
20%
13%
20%



Cutoff 3
44.3
22.4
33.0
22.1



Sens 3
90%
91%
90%
91%



Spec 3
18%
 8%
 9%
 7%



Cutoff 4
239
239
295
239



Sens 4
39%
32%
22%
34%



Spec 4
70%
70%
70%
70%



Cutoff 5
360
363
464
360



Sens 5
28%
21%
18%
25%



Spec 5
80%
80%
80%
80%



Cutoff 6
725
732
805
725



Sens 6
18%
11%
 8%
14%



Spec 6
90%
90%
90%
90%



OR Quart 2
1.1
0.69
1.1
0.48



p Value
0.64
0.34
0.83
0.082



95% CI of
0.70
0.32
0.48
0.21



OR Quart2
1.8
1.5
2.5
1.1



OR Quart 3
1.5
1.1
1.1
0.94



p Value
0.070
0.86
0.83
0.87



95% CI of
0.97
0.53
0.48
0.47



OR Quart3
2.4
2.1
2.5
1.9



OR Quart 4
1.7
1.1
1.4
1.1



p Value
0.015
0.72
0.42
0.72



95% CI of
1.1
0.57
0.63
0.58



OR Quart4
2.7
2.3
3.0
2.2
















TABLE 2





Comparison of marker levels in urine samples collected from Cohort


1 (patients that did not progress beyond RIFLE stage 0 or R) and in urine samples


collected from subjects at 0, 24 hours, and 48 hours prior to reaching stage I or F in Cohort 2.







Serum amyloid A protein

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
1.53
1.51
1.53
1.84
1.53
0.956



Average
71.9
9.20
71.9
121
71.9
5.66



Stdev
369
16.4
369
545
369
13.2



p (t-test)

0.24

0.42

0.38



Min
0.000420
0.000420
0.000420
0.000310
0.000420
0.0684



Max
2680
89.7
2680
2680
2680
63.2



n (Samp)
364
47
364
47
364
24



n (Patient)
134
47
134
47
134
24



sCr only



Median
1.52
1.25
1.52
1.56
1.52
1.44



Average
71.4
5.28
71.4
3.33
71.4
10.5



Stdev
381
11.0
381
4.03
381
24.4



p (t-test)

0.65

0.55

0.65



Min
0.000420
0.000551
0.000420
0.801
0.000420
0.829



Max
2680
30.2
2680
14.2
2680
70.9



n (Samp)
532
7
532
11
532
8



n (Patient)
181
7
181
11
181
8



UO only



Median
1.52
1.56
1.52
1.77
1.52
0.858



Average
65.6
9.10
65.6
123
65.6
6.14



Stdev
351
16.6
351
551
351
14.0



p (t-test)

0.29

0.33

0.44



Min
0.000420
0.000420
0.000420
0.000310
0.000420
0.0684



Max
2680
89.7
2680
2680
2680
63.2



n (Samp)
402
44
402
46
402
21



n (Patient)
145
44
145
46
145
21















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.52
0.43
0.52
0.52
0.52
0.51
0.38
0.54
0.38



SE
0.045
0.11
0.046
0.045
0.089
0.045
0.063
0.10
0.067



p
0.73
0.55
0.72
0.73
0.83
0.81
0.067
0.73
0.075



nCohort 1
364
532
402
364
532
402
364
532
402



nCohort 2
47
7
44
47
11
46
24
8
21



Cutoff 1
1.02
1.25
1.00
0.945
1.08
0.945
0.532
1.36
0.521



Sens 1
70%
71%
70%
70%
73%
72%
71%
75%
71%



Spec 1
33%
43%
32%
29%
37%
29%
13%
47%
13%



Cutoff 2
0.772
0.363
0.715
0.801
1.05
0.853
0.452
1.05
0.452



Sens 2
81%
86%
82%
81%
82%
80%
83%
88%
81%



Spec 2
22%
 8%
20%
23%
36%
25%
10%
36%
10%



Cutoff 3
0.377
0.000529
0.377
0.512
0.945
0.512
0.377
0.828
0.377



Sens 3
91%
100% 
91%
91%
91%
91%
92%
100% 
90%



Spec 3
 9%
 2%
 9%
12%
31%
12%
 9%
26%
 9%



Cutoff 4
3.57
3.76
3.56
3.57
3.76
3.56
3.57
3.76
3.56



Sens 4
36%
14%
36%
32%
27%
30%
29%
25%
29%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
12.8
12.2
12.3
12.8
12.2
12.3
12.8
12.2
12.3



Sens 5
23%
14%
23%
21%
 9%
20%
12%
12%
14%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
31.3
28.4
27.4
31.3
28.4
27.4
31.3
28.4
27.4



Sens 6
 6%
14%
11%
 9%
 0%
11%
 4%
12%
 5%



Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%



OR Quart 2
1.2
2.0
0.99
0.89
4.1
1.5
0.39
>5.2
0.39



p Value
0.68
0.57
0.98
0.80
0.21
0.37
0.26
<0.14
0.26



95% CI of
0.51
0.18
0.41
0.36
0.45
0.61
0.073
>0.60
0.074



OR Quart 2
2.8
22
2.4
2.2
37
3.7
2.0
na
2.0



OR Quart 3
0.89
2.0
0.90
1.3
4.1
1.5
1.2
>2.0
0.79



p Value
0.80
0.57
0.82
0.54
0.21
0.37
0.76
<0.57
0.73



95% CI of
0.36
0.18
0.37
0.56
0.45
0.61
0.36
>0.18
0.21



OR Quart 3
2.2
22
2.2
3.0
37
3.7
4.1
na
3.0



OR Quart 4
1.2
2.0
1.1
1.1
2.0
1.2
2.4
>1.0
2.1



p Value
0.68
0.57
0.84
0.84
0.57
0.64
0.13
<1.00
0.18



95% CI of
0.51
0.18
0.46
0.46
0.18
0.50
0.79
>0.062
0.70



OR Quart 4
2.8
23
2.6
2.6
22
3.1
7.1
na
6.4











Tissue-type plasminogen activator

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
0.135
0.0624
0.135
1.13
0.135
0.00726



Average
55.3
12.6
55.3
29.7
55.3
14.7



Stdev
348
32.5
348
59.2
348
36.9



p (t-test)

0.40

0.61

0.57



Min
0.00252
0.00252
0.00252
0.00252
0.00252
0.00252



Max
4790
190
4790
274
4790
127



n (Samp)
364
47
364
47
364
24



n (Patient)
134
47
134
47
134
24



sCr only



Median
0.135
0.00567
0.135
0.0624
0.135
0.00647



Average
46.5
0.110
46.5
80.7
46.5
4.87



Stdev
291
0.254
291
222
291
9.45



p (t-test)

0.67

0.70

0.69



Min
0.00252
0.00252
0.00252
0.00314
0.00252
0.00297



Max
4790
0.685
4790
741
4790
25.0



n (Samp)
532
7
532
11
532
8



n (Patient)
181
7
181
11
181
8



UO only



Median
0.135
0.0624
0.135
3.45
0.135
0.0624



Average
52.2
14.4
52.2
30.6
52.2
16.9



Stdev
331
33.7
331
59.6
331
39.1



p (t-test)

0.45

0.66

0.63



Min
0.00252
0.00297
0.00252
0.00252
0.00252
0.00252



Max
4790
190
4790
274
4790
127



n (Samp)
402
44
402
46
402
21



n (Patient)
145
44
145
46
145
21















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.43
0.26
0.46
0.54
0.50
0.55
0.40
0.36
0.44



SE
0.046
0.11
0.047
0.045
0.088
0.046
0.063
0.11
0.066



p
0.12
0.028
0.37
0.42
0.97
0.24
0.096
0.20
0.36



nCohort 1
364
532
402
364
532
402
364
532
402



nCohort 2
47
7
44
47
11
46
24
8
21



Cutoff 1
0.00503
0.00314
0.00503
0.00567
0.00564
0.00567
0.00503
0.00314
0.00564



Sens 1
77%
86%
77%
72%
82%
74%
71%
75%
71%



Spec 1
21%
12%
21%
30%
28%
32%
21%
12%
28%



Cutoff 2
0.00453
0.00314
0.00453
0.00564
0.00564
0.00564
0.00297
0.00297
0.00453



Sens 2
81%
86%
82%
81%
82%
80%
88%
88%
86%



Spec 2
17%
12%
18%
27%
28%
28%
 8%
 8%
18%



Cutoff 3
0.00297
0
0.00297
0.00297
0.00314
0.00297
0.00252
0.00252
0.00297



Sens 3
91%
100% 
93%
94%
91%
91%
96%
100% 
90%



Spec 3
 8%
 0%
 8%
 8%
12%
 8%
 4%
 4%
 8%



Cutoff 4
11.7
13.2
11.6
11.7
13.2
11.6
11.7
13.2
11.6



Sens 4
23%
 0%
27%
40%
18%
41%
21%
25%
24%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
28.4
28.1
28.1
28.4
28.1
28.1
28.4
28.1
28.1



Sens 5
15%
 0%
18%
23%
18%
26%
12%
 0%
14%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
63.4
67.8
67.8
63.4
67.8
67.8
63.4
67.8
67.8



Sens 6
 6%
 0%
 5%
17%
18%
15%
12%
 0%
14%



Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%



OR Quart 2
1.1
>1.0
0.69
2.5
1.5
2.0
1.7
1.0
1.7



p Value
0.81
<1.00
0.46
0.055
0.65
0.17
0.47
1.0
0.48



95% CI of
0.44
>0.062
0.25
0.98
0.25
0.75
0.40
0.062
0.40



OR Quart 2
2.9
na
1.9
6.4
9.2
5.1
7.3
16
7.3



OR Quart 3
1.8
>3.1
1.6
1.5
2.0
1.8
3.2
3.0
2.4



p Value
0.20
<0.33
0.29
0.46
0.42
0.24
0.088
0.34
0.21



95% CI of
0.74
>0.32
0.68
0.53
0.37
0.68
0.84
0.31
0.61



OR Quart 3
4.3
na
3.7
4.0
11
4.8
12
30
9.7



OR Quart 4
1.5
>3.1
1.2
2.1
1.0
2.1
2.4
3.0
2.1



p Value
0.36
<0.33
0.64
0.12
0.99
0.12
0.21
0.34
0.31



95% CI of
0.62
>0.32
0.51
0.82
0.14
0.83
0.61
0.31
0.51



OR Quart 4
3.7
na
3.0
5.5
7.3
5.5
9.7
30
8.5











Protein S100-B

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
nd
nd
0.0871
6.21
nd
nd



Average
nd
nd
8.11
104
nd
nd



Stdev
nd
nd
16.8
317
nd
nd



p (t-test)
nd
nd

0.0029
nd
nd



Min
nd
nd
0.0517
0.0517
nd
nd



Max
nd
nd
88.3
1240
nd
nd



n (Samp)
nd
nd
99
15
nd
nd



n (Patient)
nd
nd
77
15
nd
nd



sCr only



Median
nd
nd
0.0871
23.8
nd
nd



Average
nd
nd
20.1
20.8
nd
nd



Stdev
nd
nd
118
16.4
nd
nd



p (t-test)
nd
nd

0.99
nd
nd



Min
nd
nd
0.0517
3.13
nd
nd



Max
nd
nd
1240
35.5
nd
nd



n (Samp)
nd
nd
112
3
nd
nd



n (Patient)
nd
nd
88
3
nd
nd



UO only



Median
nd
nd
0.0871
4.98
0.0871
14.2



Average
nd
nd
9.60
108
9.60
14.2



Stdev
nd
nd
20.4
329
20.4
15.7



p (t-test)
nd
nd

0.0063

0.75



Min
nd
nd
0.0517
0.0517
0.0517
3.13



Max
nd
nd
105
1240
105
25.3



n (Samp)
nd
nd
84
14
84
2



n (Patient)
nd
nd
65
14
65
2















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
nd
nd
nd
0.71
0.82
0.65
nd
nd
0.77



SE
nd
nd
nd
0.079
0.15
0.085
nd
nd
0.20



p
nd
nd
nd
0.0087
0.037
0.069
nd
nd
0.17



nCohort 1
nd
nd
nd
99
112
84
nd
nd
84



nCohort 2
nd
nd
nd
15
3
14
nd
nd
2



Cutoff 1
nd
nd
nd
0.755
1.55
0.0871
nd
nd
1.55



Sens 1
nd
nd
nd
73%
100% 
71%
nd
nd
100% 



Spec 1
nd
nd
nd
62%
65%
57%
nd
nd
65%



Cutoff 2
nd
nd
nd
0.174
1.55
0
nd
nd
1.55



Sens 2
nd
nd
nd
80%
100% 
100% 
nd
nd
100% 



Spec 2
nd
nd
nd
60%
65%
 0%
nd
nd
65%



Cutoff 3
nd
nd
nd
0
1.55
0
nd
nd
1.55



Sens 3
nd
nd
nd
100% 
100% 
100% 
nd
nd
100% 



Spec 3
nd
nd
nd
 0%
65%
 0%
nd
nd
65%



Cutoff 4
nd
nd
nd
6.21
6.21
6.21
nd
nd
6.21



Sens 4
nd
nd
nd
47%
67%
43%
nd
nd
50%



Spec 4
nd
nd
nd
73%
71%
71%
nd
nd
71%



Cutoff 5
nd
nd
nd
12.4
14.0
13.6
nd
nd
13.6



Sens 5
nd
nd
nd
47%
67%
43%
nd
nd
50%



Spec 5
nd
nd
nd
81%
81%
81%
nd
nd
81%



Cutoff 6
nd
nd
nd
23.8
26.8
26.8
nd
nd
26.8



Sens 6
nd
nd
nd
33%
33%
29%
nd
nd
 0%



Spec 6
nd
nd
nd
91%
91%
92%
nd
nd
92%



OR Quart 2
nd
nd
nd
0.46
>0
0.29
nd
nd
>0



p Value
nd
nd
nd
0.54
<na
0.30
nd
nd
<na



95% CI of
nd
nd
nd
0.040
>na
0.028
nd
nd
>na



OR Quart 2
nd
nd
nd
5.4
na
3.0
nd
nd
na



OR Quart 3
nd
nd
nd
2.8
>1.0
1.4
nd
nd
>1.0



p Value
nd
nd
nd
0.24
<1.0
0.68
nd
nd
<0.97



95% CI of
nd
nd
nd
0.50
>0.060
0.28
nd
nd
>0.061



OR Quart 3
nd
nd
nd
16
na
7.1
nd
nd
na



OR Quart 4
nd
nd
nd
4.1
>2.1
2.2
nd
nd
>1.0



p Value
nd
nd
nd
0.096
<0.56
0.31
nd
nd
<1.0



95% CI of
nd
nd
nd
0.78
>0.18
0.48
nd
nd
>0.059



OR Quart 4
nd
nd
nd
22
na
10
nd
nd
na











Serum albumin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
24900
50700
24900
49700
24900
16900



Average
56500
99500
56500
110000
56500
61200



Stdev
123000
152000
123000
204000
123000
145000



p (t-test)

0.0016

1.6E−4

0.80



Min
0.846
1.10
0.846
1.68
0.846
1.10



Max
1650000
1120000
1650000
1280000
1650000
958000



n (Samp)
921
95
921
99
921
48



n (Patient)
343
95
343
99
343
48



sCr only



Median
28100
38300
28100
54400
28100
52200



Average
72700
77100
72700
100000
72700
79200



Stdev
162000
94200
162000
182000
162000
82100



p (t-test)

0.89

0.34

0.84



Min
0.846
5430
0.846
227
0.846
1.10



Max
1780000
418000
1780000
1010000
1780000
324000



n (Samp)
1402
26
1402
32
1402
25



n (Patient)
437
26
437
32
437
25



UO only



Median
26300
50700
26300
49600
26300
14800



Average
61500
102000
61500
101000
61500
52200



Stdev
139000
156000
139000
188000
139000
153000



p (t-test)

0.0100

0.012

0.69



Min
0.846
1.10
0.846
1.68
0.846
1.10



Max
1830000
1120000
1830000
1280000
1830000
958000



n (Samp)
1027
85
1027
91
1027
39



n (Patient)
355
85
355
91
355
39















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.64
0.59
0.63
0.63
0.59
0.62
0.48
0.60
0.42


SE
0.032
0.059
0.033
0.031
0.053
0.032
0.043
0.060
0.049


p
7.9E−6
0.12
5.8E−5
3.9E−5
0.083
3.7E−4
0.62
0.11
0.091


nCohort 1
921
1402
1027
921
1402
1027
921
1402
1027


nCohort 2
95
26
85
99
32
91
48
25
39


Cutoff 1
25100
25600
22900
19900
15200
19900
10700
17100
9370


Sens 1
71%
73%
71%
71%
72%
70%
71%
72%
72%


Spec 1
51%
48%
46%
44%
35%
43%
29%
38%
24%


Cutoff 2
16400
16400
16400
12800
12800
12800
8450
12500
4530


Sens 2
80%
81%
80%
81%
81%
80%
81%
80%
82%


Spec 2
39%
37%
38%
33%
30%
31%
24%
30%
13%


Cutoff 3
6870
6800
6800
5770
3130
8090
3700
5170
3130


Sens 3
91%
92%
91%
91%
91%
90%
92%
92%
92%


Spec 3
19%
18%
18%
17%
 9%
21%
12%
14%
10%


Cutoff 4
47700
55400
50300
47700
55400
50300
47700
55400
50300


Sens 4
53%
38%
51%
53%
47%
48%
27%
44%
18%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
72500
84400
76700
72500
84400
76700
72500
84400
76700


Sens 5
35%
27%
36%
35%
34%
32%
19%
40%
13%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
112000
152000
123000
112000
152000
123000
112000
152000
123000


Sens 6
26%
15%
24%
22%
16%
21%
12%
20%
 5%


Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%


OR Quart 2
1.9
1.5
1.9
1.5
1.4
1.6
0.91
1.5
1.5


p Value
0.100
0.53
0.13
0.29
0.57
0.20
0.83
0.53
0.43


95% CI of
0.89
0.42
0.84
0.72
0.44
0.77
0.38
0.42
0.53


OR Quart 2
4.0
5.4
4.1
3.0
4.5
3.4
2.2
5.4
4.3


OR Quart 3
2.7
2.3
2.4
1.8
1.6
2.2
1.6
1.00
2.0


p Value
0.0062
0.17
0.023
0.095
0.41
0.030
0.24
1.00
0.16


95% CI of
1.3
0.70
1.1
0.90
0.52
1.1
0.73
0.25
0.76


OR Quart 3
5.6
7.5
5.2
3.5
5.0
4.5
3.5
4.0
5.5


OR Quart 4
3.6
1.8
3.7
3.3
2.4
3.2
0.91
2.8
2.1


p Value
2.9E−4
0.37
3.8E−4
2.3E−4
0.097
8.3E−4
0.83
0.081
0.16


95% CI of
1.8
0.51
1.8
1.7
0.85
1.6
0.38
0.88
0.76


OR Quart 4
7.3
6.1
7.7
6.2
7.0
6.3
2.2
8.9
5.6










Cortisol

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2



sCr or UO



Median
149
179
149
178
149
116



Average
280
327
280
321
280
283



Stdev
329
357
329
346
329
370



p (t-test)

0.11

0.16

0.93



Min
0.000854
11.2
0.000854
14.8
0.000854
16.4



Max
1500
1500
1500
1500
1500
1500



n (Samp)
1500
146
1500
141
1500
82



n (Patient)
584
146
584
141
584
82



sCr only



Median
161
183
161
83.9
161
95.7



Average
298
366
298
213
298
217



Stdev
338
447
338
323
338
275



p (t-test)

0.23

0.095

0.13



Min
0.000854
31.5
0.000854
20.4
0.000854
15.5



Max
1500
1500
1500
1490
1500
1010



n (Samp)
2154
37
2154
45
2154
40



n (Patient)
715
37
715
45
715
40



UO only



Median
152
157
152
206
152
128



Average
284
305
284
333
284
325



Stdev
332
338
332
336
332
399



p (t-test)

0.47

0.11

0.33



Min
1.43
11.2
1.43
14.8
1.43
16.4



Max
1500
1500
1500
1500
1500
1500



n (Samp)
1532
132
1532
127
1532
66



n (Patient)
534
132
534
127
534
66















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.55
0.50
0.54
0.54
0.37
0.57
0.45
0.40
0.48



SE
0.026
0.048
0.027
0.026
0.045
0.027
0.033
0.048
0.037



p
0.069
0.94
0.15
0.094
0.0053
0.014
0.17
0.044
0.67



nCohort 1
1500
2154
1532
1500
2154
1532
1500
2154
1532



nCohort 2
146
37
132
141
45
127
82
40
66



Cutoff 1
109
57.8
109
98.8
55.3
113
54.7
62.3
58.2



Sens 1
71%
70%
70%
70%
71%
70%
71%
70%
71%



Spec 1
38%
19%
39%
35%
18%
39%
18%
21%
20%



Cutoff 2
69.2
44.9
73.8
68.5
44.9
82.3
39.7
33.3
48.2



Sens 2
80%
81%
80%
80%
80%
80%
80%
80%
80%



Spec 2
25%
13%
27%
24%
13%
29%
13%
10%
16%



Cutoff 3
45.1
32.0
50.4
39.3
32.4
48.6
30.3
30.3
23.2



Sens 3
90%
92%
90%
90%
91%
91%
90%
90%
91%



Spec 3
15%
 9%
16%
13%
 9%
16%
 9%
 8%
 5%



Cutoff 4
272
301
276
272
301
276
272
301
276



Sens 4
33%
32%
30%
36%
13%
36%
29%
20%
32%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
428
491
424
428
491
424
428
491
424



Sens 5
25%
30%
21%
26%
13%
27%
21%
12%
24%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
756
838
760
756
838
760
756
838
760



Sens 6
14%
16%
12%
14%
 7%
13%
15%
 8%
20%



Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%



OR Quart 2
1.2
0.58
1.7
1.2
1.2
1.5
0.89
1.1
0.66



p Value
0.45
0.25
0.039
0.51
0.78
0.20
0.74
0.79
0.27



95% CI of
0.73
0.23
1.0
0.71
0.39
0.82
0.46
0.41
0.31



OR Quart 2
2.0
1.5
2.9
2.0
3.5
2.6
1.7
3.2
1.4



OR Quart 3
1.2
0.33
1.4
1.4
2.4
1.9
0.89
1.4
0.77



p Value
0.52
0.055
0.27
0.21
0.080
0.018
0.73
0.47
0.47



95% CI of
0.71
0.11
0.79
0.84
0.90
1.1
0.46
0.54
0.38



OR Quart 3
2.0
1.0
2.4
2.3
6.2
3.4
1.7
3.8
1.6



OR Quart 4
1.6
1.2
1.5
1.4
3.1
1.8
1.6
2.2
1.2



p Value
0.073
0.69
0.11
0.21
0.018
0.032
0.14
0.092
0.51



95% CI of
0.96
0.54
0.91
0.83
1.2
1.1
0.87
0.88
0.65



OR Quart 4
2.5
2.6
2.6
2.3
7.8
3.2
2.9
5.4
2.3

















TABLE 3





Comparison of marker levels in urine samples collected within 12


hours of reaching stage R from Cohort 1 (patients that reached, but did not progress


beyond, RIFLE stage R) and from Cohort 2 (patients that reached RIFLE stage I or F).







Glial cell line-derived neurotrophic factor















sCr or UO

UO only















Cohort 1
Cohort 2
Cohort 1
Cohort 2







Median
0.200
0.00569
0.200
0.200



Average
0.284
0.282
0.305
0.496



Stdev
0.269
0.621
0.285
0.885



p (t-test)

0.99

0.45



Min
0.00388
0.00388
0.00388
0.00388



Max
1.01
2.07
1.01
2.07



n (Samp)
22
11
16
5



n (Patient)
22
11
16
5














At Enrollment













sCr or UO
UO only







AUC
0.31
0.43



SE
0.10
0.15



p
0.064
0.62



nCohort 1
22
16



nCohort 2
11
5



Cutoff 1
0
0.00388



Sens 1
100% 
80%



Spec 1
 0%
12%



Cutoff 2
0
0.00388



Sens 2
100% 
80%



Spec 2
 0%
12%



Cutoff 3
0
0



Sens 3
100% 
100% 



Spec 3
 0%
 0%



Cutoff 4
0.422
0.422



Sens 4
18%
20%



Spec 4
77%
75%



Cutoff 5
0.604
0.604



Sens 5
 9%
20%



Spec 5
95%
94%



Cutoff 6
0.604
0.604



Sens 6
 9%
20%



Spec 6
95%
94%



OR Quart 2
1.2
1.2



p Value
0.89
0.89



95% CI of
0.12
0.058



OR Quart 2
11
27



OR Quart 3
1.2
3.3



p Value
0.89
0.40



95% CI of
0.12
0.20



OR Quart 3
11
55



OR Quart 4
5.8
1.2



p Value
0.10
0.89



95% CI of
0.70
0.058



OR Quart 4
49
27











Serum albumin














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
36300
52600
26900
54400
36800
51100


Average
70200
154000
86500
87200
70900
154000


Stdev
91500
267000
161000
101000
90600
273000


p (t-test)

6.4E−4

0.98

0.0015


Min
1.68
1.10
831
4870
1.68
1.10


Max
495000
1480000
958000
380000
495000
1480000


n (Samp)
143
101
46
26
130
85


n (Patient)
143
101
46
26
130
85












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.58
0.58
0.58



SE
0.037
0.071
0.040



p
0.028
0.28
0.050



nCohort 1
143
46
130



nCohort 2
101
26
85



Cutoff 1
23200
16600
27800



Sens 1
70%
73%
71%



Spec 1
37%
37%
36%



Cutoff 2
15700
12800
16100



Sens 2
80%
81%
80%



Spec 2
26%
26%
23%



Cutoff 3
9350
9350
10100



Sens 3
90%
92%
91%



Spec 3
15%
13%
15%



Cutoff 4
68100
59800
67300



Sens 4
43%
46%
41%



Spec 4
71%
72%
70%



Cutoff 5
109000
117000
93800



Sens 5
33%
23%
34%



Spec 5
80%
80%
80%



Cutoff 6
169000
264000
159000



Sens 6
24%
 8%
24%



Spec 6
90%
91%
90%



OR Quart 2
0.87
0.77
0.75



p Value
0.71
0.72
0.49



95% CI of
0.41
0.19
0.34



OR Quart 2
1.8
3.2
1.7



OR Quart 3
1.1
1.6
1.2



p Value
0.85
0.50
0.60



95% CI of
0.52
0.41
0.56



OR Quart 3
2.2
6.2
2.7



OR Quart 4
1.9
1.3
1.9



p Value
0.071
0.73
0.097



95% CI of
0.95
0.33
0.89



OR Quart 4
4.0
5.0
4.2

















TABLE 4





Comparison of the maximum marker levels in urine samples


collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0) and the


maximum values in urine samples collected from subjects between enrollment and 0, 24


hours, and 48 hours prior to reaching stage F in Cohort 2.







Serum amyloid A protein

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
4.03
9.62
4.03
10.1
4.03
2.13



Average
218
177
218
188
218
8.51



Stdev
678
667
678
689
678
10.2



p (t-test)

0.83

0.88

0.33



Min
0.435
0.911
0.435
0.829
0.435
0.779



Max
2680
2680
2680
2680
2680
30.7



n (Samp)
56
16
56
15
56
10



n (Patient)
56
16
56
15
56
10



sCr only



Median
4.33
2.23
4.33
2.23
4.33
2.23



Average
190
9.34
190
9.29
190
9.24



Stdev
623
10.5
623
10.5
623
10.6



p (t-test)

0.39

0.39

0.39



Min
0.249
1.25
0.249
0.829
0.249
0.779



Max
2680
30.7
2680
30.7
2680
30.7



n (Samp)
140
9
140
9
140
9



n (Patient)
140
9
140
9
140
9



UO only



Median
3.47
9.62
3.47
10.1
3.47
1.99



Average
187
278
187
308
187
8.92



Stdev
616
844
616
889
616
14.5



p (t-test)

0.68

0.60

0.57



Min
0.435
0.911
0.435
0.911
0.435
1.05



Max
2680
2680
2680
2680
2680
30.7



n (Samp)
76
10
76
9
76
4



n (Patient)
76
10
76
9
76
4















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.50
0.45
0.56
0.49
0.43
0.55
0.38
0.42
0.37



SE
0.082
0.10
0.100
0.085
0.10
0.10
0.10
0.10
0.15



p
0.99
0.59
0.57
0.87
0.51
0.64
0.23
0.43
0.39



nCohort 1
56
140
76
56
140
76
56
140
76



nCohort 2
16
9
10
15
9
9
10
9
4



Cutoff 1
1.96
1.36
6.33
1.96
1.36
2.01
1.88
1.36
1.88



Sens 1
75%
78%
70%
73%
78%
78%
70%
78%
75%



Spec 1
25%
21%
58%
25%
21%
30%
23%
21%
26%



Cutoff 2
1.30
1.27
2.01
1.30
1.27
1.05
1.30
0.779
1.05



Sens 2
81%
89%
80%
80%
89%
89%
80%
89%
100% 



Spec 2
14%
19%
30%
14%
19%
 9%
14%
 6%
 9%



Cutoff 3
1.17
1.25
1.05
0.873
0.770
0.873
0.779
0.770
1.05



Sens 3
94%
100% 
90%
93%
100% 
100% 
90%
100% 
100% 



Spec 3
12%
18%
 9%
 9%
 6%
 8%
 5%
 6%
 9%



Cutoff 4
19.7
19.7
19.7
19.7
19.7
19.7
19.7
19.7
19.7



Sens 4
19%
11%
30%
20%
11%
33%
10%
11%
25%



Spec 4
71%
70%
71%
71%
70%
71%
71%
70%
71%



Cutoff 5
28.7
27.1
28.4
28.7
27.1
28.4
28.7
27.1
28.4



Sens 5
19%
11%
30%
20%
11%
33%
10%
11%
25%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
76.9
63.2
76.9
76.9
63.2
76.9
76.9
63.2
76.9



Sens 6
 6%
 0%
10%
 7%
 0%
11%
 0%
 0%
 0%



Spec 6
91%
90%
91%
91%
90%
91%
91%
90%
91%



OR Quart 2
3.2
3.3
0.45
2.5
3.3
0.48
3.7
3.3
0



p Value
0.15
0.32
0.53
0.26
0.32
0.56
0.28
0.32
na



95% CI of
0.67
0.32
0.038
0.51
0.32
0.040
0.34
0.32
na



OR Quart 2
15
33
5.4
12
33
5.7
40
33
na



OR Quart 3
0.62
2.1
2.2
0.62
2.1
1.6
3.4
2.1
2.1



p Value
0.63
0.55
0.39
0.63
0.55
0.64
0.31
0.55
0.56



95% CI of
0.091
0.18
0.36
0.091
0.18
0.24
0.32
0.18
0.18



OR Quart 3
4.3
24
14
4.3
24
11
37
24
25



OR Quart 4
1.4
3.3
1.5
1.5
3.3
1.5
3.7
3.3
1.0



p Value
0.67
0.32
0.68
0.61
0.32
0.68
0.28
0.32
1.0



95% CI of
0.27
0.32
0.22
0.29
0.32
0.22
0.34
0.32
0.058



OR Quart 4
7.5
33
10
8.2
33
10
40
33
17











Tissue-type plasminogen activator

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
29.1
20.8
29.1
20.9
29.1
17.2



Average
158
46.1
158
49.1
158
37.5



Stdev
564
56.4
564
57.0
564
43.1



p (t-test)

0.43

0.46

0.50



Min
0.00252
0.00567
0.00252
0.00567
0.00252
0.00252



Max
3940
171
3940
171
3940
111



n (Samp)
56
16
56
15
56
10



n (Patient)
56
16
56
15
56
10



sCr only



Median
21.3
20.7
21.3
20.7
21.3
20.7



Average
132
41.6
132
41.6
132
41.6



Stdev
540
43.5
540
43.5
540
43.5



p (t-test)

0.62

0.62

0.62



Min
0.00252
0.00567
0.00252
0.00567
0.00252
0.00314



Max
4790
111
4790
111
4790
111



n (Samp)
140
9
140
9
140
9



n (Patient)
140
9
140
9
140
9



UO only



Median
26.2
20.8
26.2
20.9
26.2
15.1



Average
145
43.3
145
48.1
145
17.6



Stdev
512
61.8
512
63.5
512
17.3



p (t-test)

0.53

0.57

0.62



Min
0.00252
0.00567
0.00252
0.00567
0.00252
0.00252



Max
3940
171
3940
171
3940
40.3



n (Samp)
76
10
76
9
76
4



n (Patient)
76
10
76
9
76
4















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.43
0.51
0.43
0.46
0.51
0.48
0.42
0.50
0.36



SE
0.083
0.10
0.100
0.085
0.10
0.10
0.10
0.100
0.15



p
0.41
0.94
0.51
0.62
0.94
0.81
0.42
0.98
0.36



nCohort 1
56
140
76
56
140
76
56
140
76



nCohort 2
16
9
10
15
9
9
10
9
4



Cutoff 1
0.00567
11.7
8.47
7.83
11.7
8.47
7.83
11.7
8.47



Sens 1
75%
78%
70%
73%
78%
78%
70%
78%
75%



Spec 1
 5%
44%
37%
32%
44%
37%
32%
44%
37%



Cutoff 2
0.00297
0.00564
0.00567
0.00567
0.00564
0.00567
0.00314
0.00564
0



Sens 2
100% 
100% 
80%
80%
100% 
89%
80%
89%
100% 



Spec 2
 4%
 6%
 8%
 5%
 6%
 8%
 4%
 6%
 0%



Cutoff 3
0.00297
0.00564
0.00453
0.00297
0.00564
0.00453
0.00297
0.00297
0



Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
90%
100% 
100% 



Spec 3
 4%
 6%
 5%
 4%
 6%
 5%
 4%
 2%
 0%



Cutoff 4
63.4
54.6
56.3
63.4
54.6
56.3
63.4
54.6
56.3



Sens 4
31%
33%
20%
33%
33%
22%
30%
33%
 0%



Spec 4
71%
70%
71%
71%
70%
71%
71%
70%
71%



Cutoff 5
77.0
81.6
77.0
77.0
81.6
77.0
77.0
81.6
77.0



Sens 5
25%
22%
20%
27%
22%
22%
20%
22%
 0%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
246
192
192
246
192
192
246
192
192



Sens 6
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%



Spec 6
91%
90%
91%
91%
90%
91%
91%
90%
91%



OR Quart 2
0.15
1.5
1.1
0.15
1.5
1.1
0.31
1.5
>1.1



p Value
0.10
0.65
0.96
0.10
0.65
0.96
0.34
0.65
<0.97



95% CI of
0.016
0.24
0.13
0.016
0.24
0.13
0.029
0.24
>0.061



OR Quart 2
1.5
9.8
8.2
1.5
9.8
8.2
3.4
9.8
na



OR Quart 3
1.0
0.49
1.6
1.0
0.49
1.7
1.0
0.49
>2.2



p Value
1.0
0.56
0.64
1.0
0.56
0.60
1.0
0.56
<0.53



95% CI of
0.23
0.042
0.24
0.23
0.042
0.25
0.17
0.042
>0.19



OR Quart 3
4.3
5.6
11
4.3
5.6
11
5.8
5.6
na



OR Quart 4
1.0
1.5
1.7
0.80
1.5
1.1
1.1
1.5
>1.1



p Value
1.0
0.67
0.60
0.77
0.67
0.96
0.93
0.67
<0.97



95% CI of
0.23
0.24
0.25
0.17
0.24
0.13
0.18
0.24
>0.061



OR Quart 4
4.3
9.5
11
3.7
9.5
8.2
6.3
9.5
na











Protein S100-B

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
0.0871
19.8
0.0871
19.8
0.0871
10.3



Average
6.14
178
6.14
178
6.14
32.9



Stdev
14.2
432
14.2
432
14.2
42.7



p (t-test)

0.0082

0.0082

0.0095



Min
0.0517
3.13
0.0517
3.13
0.0517
6.21



Max
79.8
1240
79.8
1240
79.8
82.1



n (Samp)
44
8
44
8
44
3



n (Patient)
44
8
44
8
44
3



sCr only



Median
0.0871
15.0
0.0871
15.0
nd
nd



Average
24.0
17.2
24.0
17.2
nd
nd



Stdev
143
15.2
143
15.2
nd
nd



p (t-test)

0.92

0.92
nd
nd



Min
0.0517
3.13
0.0517
3.13
nd
nd



Max
1240
35.5
1240
35.5
nd
nd



n (Samp)
76
4
76
4
nd
nd



n (Patient)
76
4
76
4
nd
nd



UO only



Median
0.0871
15.7
0.0871
15.7
0.0871
10.3



Average
8.70
272
8.70
272
8.70
32.9



Stdev
20.1
545
20.1
545
20.1
42.7



p (t-test)

0.0028

0.0028

0.074



Min
0.0517
6.21
0.0517
6.21
0.0517
6.21



Max
88.3
1240
88.3
1240
88.3
82.1



n (Samp)
37
5
37
5
37
3



n (Patient)
37
5
37
5
37
3















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.88
0.80
0.86
0.88
0.80
0.86
0.84
nd
0.82



SE
0.082
0.14
0.11
0.082
0.14
0.11
0.15
nd
0.15



p
3.7E−6
0.028
6.6E−4
3.7E−6
0.028
6.6E−4
0.019
nd
0.036



nCohort 1
44
76
37
44
76
37
44
nd
37



nCohort 2
8
4
5
8
4
5
3
nd
3



Cutoff 1
6.21
3.13
6.21
6.21
3.13
6.21
1.55
nd
1.55



Sens 1
75%
75%
80%
75%
75%
80%
100% 
nd
100% 



Spec 1
75%
67%
73%
75%
67%
73%
73%
nd
70%



Cutoff 2
3.13
1.55
6.21
3.13
1.55
6.21
1.55
nd
1.55



Sens 2
88%
100% 
80%
88%
100% 
80%
100% 
nd
100% 



Spec 2
73%
67%
73%
73%
67%
73%
73%
nd
70%



Cutoff 3
1.55
1.55
1.55
1.55
1.55
1.55
1.55
nd
1.55



Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
100% 
nd
100% 



Spec 3
73%
67%
70%
73%
67%
70%
73%
nd
70%



Cutoff 4
1.55
6.21
1.55
1.55
6.21
1.55
1.55
nd
1.55



Sens 4
100% 
50%
100% 
100% 
50%
100% 
100% 
nd
100% 



Spec 4
73%
71%
70%
73%
71%
70%
73%
nd
70%



Cutoff 5
10.3
13.6
10.3
10.3
13.6
10.3
10.3
nd
10.3



Sens 5
62%
50%
60%
62%
50%
60%
33%
nd
33%



Spec 5
82%
80%
81%
82%
80%
81%
82%
nd
81%



Cutoff 6
23.8
23.8
26.8
23.8
23.8
26.8
23.8
nd
26.8



Sens 6
38%
25%
40%
38%
25%
40%
33%
nd
33%



Spec 6
93%
91%
92%
93%
91%
92%
93%
nd
92%



OR Quart 2
>0
>0
>0
>0
>0
>0
>0
nd
>0



p Value
<na
<na
<na
<na
<na
<na
<na
nd
<na



95% CI of
>na
>na
>na
>na
>na
>na
>na
nd
>na



OR Quart 2
na
na
na
na
na
na
na
nd
na



OR Quart 3
>3.9
>2.2
>2.5
>3.9
>2.2
>2.5
>2.2
nd
>2.5



p Value
<0.27
<0.53
<0.49
<0.27
<0.53
<0.49
<0.54
nd
<0.49



95% CI of
>0.35
>0.19
>0.19
>0.35
>0.19
>0.19
>0.17
nd
>0.19



OR Quart 3
na
na
na
na
na
na
na
nd
na



OR Quart 4
>8.1
>2.2
>3.8
>8.1
>2.2
>3.8
>1.0
nd
>1.1



p Value
<0.077
<0.53
<0.29
<0.077
<0.53
<0.29
<1.0
nd
<0.94



95% CI of
>0.80
>0.19
>0.32
>0.80
>0.19
>0.32
>0.055
nd
>0.060



OR Quart 4
na
na
na
na
na
na
na
nd
na











Resistin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
54700
61700
54700
61600
54700
62600



Average
56700
67000
56700
65800
56700
70100



Stdev
25600
23300
25600
24400
25600
26600



p (t-test)

0.022

0.050

0.023



Min
2250
27200
2250
21900
2250
34300



Max
116000
150000
116000
150000
116000
150000



n (Samp)
180
39
180
37
180
22



n (Patient)
180
39
180
37
180
22



sCr only



Median
58400
66100
58400
64900
58400
67700



Average
61100
74500
61100
74100
61100
75300



Stdev
26200
23900
26200
24100
26200
27400



p (t-test)

0.017

0.020

0.029



Min
2250
48300
2250
48300
2250
36300



Max
150000
150000
150000
150000
150000
150000



n (Samp)
369
23
369
23
369
17



n (Patient)
369
23
369
23
369
17



UO only



Median
56600
59900
56600
59400
56600
60900



Average
57800
61000
57800
58400
57800
63600



Stdev
25600
22000
25600
23400
25600
24600



p (t-test)

0.58

0.92

0.46



Min
2250
27200
2250
21900
2250
34300



Max
118000
118000
118000
118000
118000
118000



n (Samp)
207
22
207
20
207
11



n (Patient)
207
22
207
20
207
11















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.62
0.65
0.54
0.60
0.65
0.50
0.64
0.65
0.56


SE
0.052
0.064
0.066
0.053
0.064
0.068
0.067
0.074
0.092


p
0.022
0.016
0.59
0.058
0.020
0.97
0.037
0.050
0.52


nCohort 1
180
369
207
180
369
207
180
369
207


nCohort 2
39
23
22
37
23
20
22
17
11


Cutoff 1
54900
60900
49800
58600
60900
47500
56600
60900
49800


Sens 1
72%
74%
73%
70%
74%
70%
73%
71%
73%


Spec 1
51%
54%
43%
56%
54%
40%
52%
54%
43%


Cutoff 2
49200
58600
47500
48100
58600
40200
49800
54200
49300


Sens 2
82%
83%
82%
81%
83%
80%
82%
82%
82%


Spec 2
42%
51%
40%
42%
51%
27%
44%
44%
41%


Cutoff 3
37600
49800
37000
37600
49300
37000
40200
49200
40200


Sens 3
92%
91%
91%
92%
91%
90%
91%
94%
91%


Spec 3
25%
38%
22%
25%
37%
22%
28%
37%
27%


Cutoff 4
66800
75100
67200
66800
75100
67200
66800
75100
67200


Sens 4
36%
35%
23%
30%
35%
15%
41%
41%
18%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
80700
87300
81300
80700
87300
81300
80700
87300
81300


Sens 5
21%
26%
14%
22%
26%
15%
27%
29%
18%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
100000
100000
100000
100000
100000
100000
100000
100000
100000


Sens 6
 5%
 9%
 5%
 5%
 9%
 5%
 9%
12%
 9%


Spec 6
98%
96%
98%
98%
96%
98%
98%
96%
98%


OR Quart 2
2.1
>5.3
1.6
1.9
>5.3
2.9
2.6
4.1
3.1


p Value
0.24
<0.13
0.51
0.35
<0.13
0.13
0.27
0.21
0.34


95% CI of
0.60
>0.60
0.42
0.51
>0.60
0.74
0.48
0.45
0.31


OR Quart 2
7.5
na
5.8
6.8
na
12
14
37
30


OR Quart 3
5.1
>12
1.9
5.3
>12
1.7
4.6
6.3
5.4


p Value
0.0063
<0.017
0.35
0.0056
<0.017
0.47
0.063
0.090
0.13


95% CI of
1.6
>1.6
0.51
1.6
>1.6
0.39
0.92
0.75
0.61


OR Quart 3
17
na
6.7
17
na
7.6
23
54
48


OR Quart 4
3.1
>7.5
1.2
2.8
>7.5
1.4
3.8
6.3
2.0


p Value
0.066
<0.061
0.75
0.10
<0.061
0.68
0.11
0.092
0.58


95% CI of
0.93
>0.91
0.32
0.81
>0.91
0.30
0.75
0.74
0.18


OR Quart 4
11
na
4.9
9.5
na
6.5
19
53
23










Parathyroid hormone

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
18.0
23.8
18.0
20.0
18.0
23.8



Average
25.5
31.0
25.5
28.4
25.5
29.9



Stdev
30.0
30.2
30.0
28.8
30.0
32.7



p (t-test)

0.24

0.54

0.45



Min
0.00103
0.00185
0.00103
0.00185
0.00103
0.0488



Max
302
160
302
160
302
160



n (Samp)
211
51
211
47
211
31



n (Patient)
211
51
211
47
211
31



sCr only



Median
22.9
24.6
22.9
25.3
22.9
23.8



Average
31.7
30.3
31.7
28.6
31.7
26.0



Stdev
38.1
24.1
38.1
20.2
38.1
19.0



p (t-test)

0.86

0.69

0.52



Min
0.00103
0.00185
0.00103
0.00185
0.00103
1.24



Max
433
96.9
433
75.7
433
72.1



n (Samp)
452
26
452
25
452
19



n (Patient)
452
26
452
25
452
19



UO only



Median
21.0
20.0
21.0
19.6
21.0
21.9



Average
29.7
29.4
29.7
26.7
29.7
30.0



Stdev
31.5
32.3
31.5
32.3
31.5
38.2



p (t-test)

0.97

0.63

0.97



Min
0.00103
0.539
0.00103
0.539
0.00103
0.0488



Max
302
160
302
160
302
160



n (Samp)
242
33
242
30
242
20



n (Patient)
242
33
242
30
242
20















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.56
0.53
0.49
0.54
0.53
0.45
0.54
0.50
0.46



SE
0.046
0.059
0.054
0.047
0.060
0.057
0.056
0.068
0.069



p
0.17
0.61
0.80
0.38
0.64
0.40
0.51
0.98
0.52



nCohort 1
211
452
242
211
452
242
211
452
242



nCohort 2
51
26
33
47
25
30
31
19
20



Cutoff 1
13.6
15.9
7.99
12.5
18.7
7.99
11.5
13.6
5.52



Sens 1
71%
73%
73%
70%
72%
70%
71%
74%
70%



Spec 1
40%
38%
23%
37%
44%
23%
36%
32%
16%



Cutoff 2
7.99
13.6
5.29
5.33
13.6
4.62
6.06
7.02
2.32



Sens 2
80%
81%
82%
81%
80%
80%
81%
84%
80%



Spec 2
29%
32%
16%
20%
32%
14%
22%
20%
11%



Cutoff 3
2.32
2.32
1.61
1.61
2.32
1.61
1.38
2.32
0.532



Sens 3
90%
92%
91%
91%
92%
90%
90%
95%
90%



Spec 3
15%
12%
 8%
11%
12%
 8%
10%
12%
 2%



Cutoff 4
30.5
35.8
35.3
30.5
35.8
35.3
30.5
35.8
35.3



Sens 4
39%
27%
27%
38%
28%
20%
35%
26%
25%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
36.9
47.5
46.0
36.9
47.5
46.0
36.9
47.5
46.0



Sens 5
25%
23%
18%
23%
20%
13%
26%
16%
15%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
53.9
66.4
64.3
53.9
66.4
64.3
53.9
66.4
64.3



Sens 6
18%
12%
 9%
13%
 8%
 7%
16%
 5%
10%



Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%



OR Quart 2
1.1
2.1
1.0
0.68
1.8
1.2
0.46
2.4
1.0



p Value
0.84
0.25
1.0
0.44
0.36
0.77
0.22
0.21
0.98



95% CI of
0.43
0.60
0.35
0.25
0.51
0.38
0.13
0.61
0.28



OR Quart 2
2.8
7.0
2.8
1.8
6.3
3.7
1.6
9.6
3.7



OR Quart 3
1.6
2.1
0.86
1.6
2.4
1.2
1.3
1.7
0.38



p Value
0.27
0.24
0.78
0.28
0.16
0.77
0.61
0.48
0.26



95% CI of
0.68
0.61
0.29
0.68
0.70
0.38
0.47
0.40
0.071



OR Quart 3
4.0
7.1
2.5
3.8
7.9
3.7
3.6
7.3
2.0



OR Quart 4
1.6
1.5
1.3
1.1
1.2
1.8
1.1
1.4
1.7



p Value
0.29
0.53
0.59
0.85
0.74
0.29
0.82
0.69
0.37



95% CI of
0.67
0.42
0.49
0.44
0.33
0.61
0.40
0.30
0.53



OR Quart 4
3.9
5.5
3.6
2.7
4.8
5.2
3.1
6.2
5.5











Serum albumin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
36200
184000
36200
156000
36200
103000



Average
84000
324000
84000
286000
84000
212000



Stdev
197000
408000
197000
399000
197000
282000



p (t-test)

1.1E−7

7.1E−6

0.0072



Min
12.7
16400
12.7
13200
12.7
12500



Max
1650000
1780000
1650000
1780000
1650000
1030000



n (Samp)
179
39
179
37
179
22



n (Patient)
179
39
179
37
179
22



sCr only



Median
51900
156000
51900
107000
51900
110000



Average
123000
225000
123000
214000
123000
230000



Stdev
239000
271000
239000
276000
239000
313000



p (t-test)

0.049

0.081

0.077



Min
1.68
16400
1.68
13200
1.68
12500



Max
1780000
1030000
1780000
1030000
1780000
1030000



n (Samp)
367
23
367
23
367
17



n (Patient)
367
23
367
23
367
17



UO only



Median
39100
227000
39100
183000
39100
96500



Average
87200
421000
87200
373000
87200
222000



Stdev
187000
488000
187000
487000
187000
297000



p (t-test)

8.3E−10

2.2E−7

0.025



Min
12.7
16900
12.7
16900
12.7
15300



Max
1650000
1780000
1650000
1780000
1650000
1030000



n (Samp)
206
22
206
20
206
11



n (Patient)
206
22
206
20
206
11















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.82
0.72
0.83
0.79
0.68
0.80
0.75
0.67
0.72


SE
0.043
0.062
0.055
0.046
0.063
0.060
0.062
0.073
0.089


p
5.8E−14
4.1E−4
3.7E−9
3.4E−10
0.0040
4.4E−7
4.6E−5
0.024
0.015


nCohort 1
179
367
206
179
367
206
179
367
206


nCohort 2
39
23
22
37
23
20
22
17
11


Cutoff 1
87300
56200
95300
56100
53700
95300
52800
53200
61800


Sens 1
72%
74%
73%
70%
74%
70%
73%
71%
73%


Spec 1
79%
53%
79%
68%
51%
79%
65%
51%
67%


Cutoff 2
54500
53700
80500
52800
48000
80500
37700
37700
33800


Sens 2
82%
83%
82%
81%
83%
80%
82%
82%
82%


Spec 2
66%
51%
73%
65%
48%
73%
52%
40%
43%


Cutoff 3
24300
29100
36400
24300
29100
29100
24300
25700
19700


Sens 3
92%
91%
91%
92%
91%
90%
91%
94%
91%


Spec 3
41%
33%
47%
41%
33%
40%
41%
31%
31%


Cutoff 4
59700
93100
72200
59700
93100
72200
59700
93100
72200


Sens 4
74%
65%
82%
68%
57%
80%
64%
53%
64%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
89500
145000
101000
89500
145000
101000
89500
145000
101000


Sens 5
69%
52%
68%
62%
43%
65%
55%
47%
45%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
147000
257000
162000
147000
257000
162000
147000
257000
162000


Sens 6
59%
22%
59%
51%
22%
55%
45%
24%
36%


Spec 6
91%
90%
90%
91%
90%
90%
91%
90%
90%


OR Quart 2
4.2
4.1
2.0
5.4
6.3
2.0
4.3
4.1
2.0


p Value
0.21
0.21
0.57
0.13
0.092
0.58
0.20
0.21
0.57


95% CI of
0.45
0.45
0.18
0.61
0.74
0.18
0.46
0.45
0.18


OR Quart 2
38
37
23
48
53
23
40
38
23


OR Quart 3
9.2
6.3
4.2
9.2
6.3
4.2
4.3
4.1
2.0


p Value
0.040
0.090
0.20
0.040
0.090
0.20
0.20
0.21
0.57


95% CI of
1.1
0.75
0.46
1.1
0.75
0.46
0.46
0.45
0.18


OR Quart 3
76
54
39
76
54
39
40
38
23


OR Quart 4
48
13
20
39
11
16
17
8.6
6.5


p Value
2.2E−4
0.014
0.0044
4.5E−4
0.024
0.0084
0.0078
0.044
0.089


95% CI of
6.1
1.7
2.5
5.1
1.4
2.0
2.1
1.1
0.75


OR Quart 4
370
110
160
310
87
130
130
70
56










Cortisol

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
213
318
213
265
213
240



Average
373
585
373
485
373
501



Stdev
371
499
371
447
371
489



p (t-test)

1.6E−4

0.042

0.064



Min
2.20
28.0
2.20
28.0
2.20
17.6



Max
1500
1500
1500
1500
1500
1500



n (Samp)
339
58
339
56
339
34



n (Patient)
339
58
339
56
339
34



sCr only



Median
275
265
275
241
275
240



Average
452
520
452
446
452
413



Stdev
411
485
411
417
411
425



p (t-test)

0.38

0.94

0.66



Min
2.20
28.0
2.20
28.0
2.20
29.2



Max
1500
1500
1500
1500
1500
1500



n (Samp)
608
30
608
30
608
22



n (Patient)
608
30
608
30
608
22



UO only



Median
239
293
239
229
239
218



Average
397
542
397
448
397
457



Stdev
384
479
384
435
384
480



p (t-test)

0.031

0.46

0.49



Min
5.03
36.0
5.03
29.2
5.03
17.6



Max
1500
1500
1500
1500
1500
1500



n (Samp)
316
39
316
37
316
22



n (Patient)
316
39
316
37
316
22















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.63
0.53
0.59
0.58
0.49
0.54
0.57
0.47
0.53



SE
0.042
0.055
0.050
0.043
0.054
0.051
0.053
0.064
0.065



p
0.0024
0.60
0.061
0.077
0.89
0.42
0.19
0.69
0.70



nCohort 1
339
608
316
339
608
316
339
608
316



nCohort 2
58
30
39
56
30
37
34
22
22



Cutoff 1
196
196
183
168
181
181
152
152
148



Sens 1
71%
70%
72%
71%
70%
70%
71%
73%
73%



Spec 1
45%
37%
39%
40%
33%
39%
36%
28%
33%



Cutoff 2
148
145
150
119
115
148
115
115
121



Sens 2
81%
80%
82%
80%
80%
81%
82%
82%
82%



Spec 2
35%
27%
33%
29%
20%
33%
27%
20%
28%



Cutoff 3
88.2
74.7
88.2
74.7
70.5
83.6
88.2
60.3
88.2



Sens 3
91%
90%
92%
91%
90%
92%
91%
91%
91%



Spec 3
19%
12%
17%
16%
10%
16%
19%
 8%
17%



Cutoff 4
431
605
465
431
605
465
431
605
465



Sens 4
47%
37%
41%
38%
33%
30%
32%
23%
27%



Spec 4
71%
70%
70%
71%
70%
70%
71%
70%
70%



Cutoff 5
693
838
707
693
838
707
693
838
707



Sens 5
38%
30%
31%
32%
23%
24%
32%
23%
27%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
983
1050
1000
983
1050
1000
983
1050
1000



Sens 6
29%
13%
18%
21%
 7%
11%
29%
 9%
14%



Spec 6
90%
90%
91%
90%
90%
91%
90%
90%
91%



OR Quart 2
1.5
1.5
2.6
1.4
0.54
2.4
1.6
1.0
2.1



p Value
0.37
0.44
0.087
0.40
0.29
0.096
0.42
0.99
0.25



95% CI of
0.61
0.53
0.87
0.61
0.18
0.86
0.53
0.29
0.60



OR Quart 2
3.7
4.4
7.7
3.4
1.7
6.5
4.6
3.5
7.2



OR Quart 3
1.4
0.66
1.9
1.3
1.0
1.4
1.4
1.4
1.0



p Value
0.49
0.52
0.28
0.52
1.0
0.58
0.58
0.56
1.0



95% CI of
0.55
0.18
0.60
0.55
0.39
0.45
0.45
0.44
0.24



OR Quart 3
3.4
2.4
5.8
3.2
2.6
4.1
4.1
4.6
4.1



OR Quart 4
3.2
1.9
2.8
2.1
0.77
1.7
1.9
1.0
1.5



p Value
0.0063
0.22
0.058
0.079
0.62
0.31
0.22
0.99
0.53



95% CI of
1.4
0.68
0.97
0.92
0.28
0.60
0.68
0.29
0.41



OR Quart 4
7.2
5.2
8.3
4.8
2.1
5.0
5.4
3.5
5.6

















TABLE 5





Comparison of marker levels in EDTA samples collected from


Cohort 1 (patients that did not progress beyond RIFLE stage 0) and in EDTA samples


collected from subjects at 0, 24 hours, and 48 hours prior to reaching stage R, I or F in


Cohort 2.







Serum amyloid A protein

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
56800
893000
56800
45200
56800
494000



Average
570000
889000
570000
625000
570000
615000



Stdev
751000
869000
751000
755000
751000
652000



p (t-test)

0.014

0.72

0.89



Min
2540
3230
2540
8670
2540
5520



Max
2630000
2630000
2630000
2630000
2630000
1340000



n (Samp)
105
60
105
32
105
6



n (Patient)
38
60
38
32
38
6



sCr only



Median
95000
893000
95000
893000
95000
556000



Average
729000
845000
729000
555000
729000
616000



Stdev
869000
952000
869000
526000
869000
612000



p (t-test)

0.58

0.55

0.80



Min
16.4
5230
16.4
17100
16.4
11600



Max
2630000
2630000
2630000
1340000
2630000
1340000



n (Samp)
268
18
268
9
268
4



n (Patient)
89
18
89
9
89
4



UO only



Median
43900
893000
43900
893000
43900
94300



Average
542000
889000
542000
727000
542000
563000



Stdev
729000
836000
729000
800000
729000
646000



p (t-test)

0.0056

0.19

0.93



Min
1150
426
1150
610
1150
559



Max
2630000
2630000
2630000
2630000
2630000
1340000



n (Samp)
137
52
137
36
137
9



n (Patient)
48
52
48
36
48
9















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.60
0.52
0.62
0.50
0.45
0.55
0.51
0.50
0.49


SE
0.047
0.071
0.047
0.059
0.10
0.055
0.12
0.15
0.10


p
0.032
0.82
0.012
0.96
0.60
0.39
0.92
0.99
0.94


nCohort 1
105
268
137
105
268
137
105
268
137


nCohort 2
60
18
52
32
9
36
6
4
9


Cutoff 1
40700
27200
44600
28300
21200
28300
15300
171000
16000


Sens 1
70%
72%
71%
72%
78%
72%
83%
75%
78%


Spec 1
41%
27%
52%
30%
19%
31%
10%
52%
11%


Cutoff 2
26800
25000
26800
18800
17500
25700
15300
10900
3730


Sens 2
80%
83%
81%
81%
89%
81%
83%
100% 
89%


Spec 2
29%
22%
30%
13%
14%
27%
10%
 8%
 3%


Cutoff 3
17400
18600
14200
12600
16000
9440
3420
10900
0


Sens 3
90%
94%
90%
91%
100% 
92%
100% 
100% 
100% 


Spec 3
10%
15%
 9%
 6%
13%
 5%
 2%
 8%
 0%


Cutoff 4
893000
893000
893000
893000
893000
893000
893000
893000
893000


Sens 4
38%
28%
40%
25%
11%
31%
33%
25%
33%


Spec 4
78%
70%
79%
78%
70%
79%
78%
70%
79%


Cutoff 5
1340000
1340000
1340000
1340000
1340000
1340000
1340000
1340000
1340000


Sens 5
13%
17%
12%
 6%
 0%
 8%
 0%
 0%
 0%


Spec 5
93%
88%
94%
93%
88%
94%
93%
88%
94%


Cutoff 6
1340000
2630000
1340000
1340000
2630000
1340000
1340000
2630000
1340000


Sens 6
13%
 0%
12%
 6%
 0%
 8%
 0%
 0%
 0%


Spec 6
93%
100% 
94%
93%
100% 
94%
93%
100% 
94%


OR Quart 2
0.89
0.57
0.87
1.6
4.2
1.4
0
0
0.24


p Value
0.81
0.46
0.79
0.40
0.20
0.58
na
na
0.21


95% CI of
0.34
0.13
0.30
0.53
0.46
0.46
na
na
0.025


OR Quart 2
2.3
2.5
2.5
4.9
39
4.1
na
na
2.2


OR Quart 3
1.7
1.0
2.2
0.83
1.0
1.4
0.96
3.1
0.23


p Value
0.25
1.0
0.11
0.76
0.99
0.58
0.97
0.33
0.20


95% CI of
0.69
0.28
0.85
0.25
0.062
0.46
0.13
0.31
0.024


OR Quart 3
4.3
3.6
5.6
2.8
17
4.1
7.4
30
2.2


OR Quart 4
2.2
0.99
2.8
1.3
3.1
1.7
0.96
0
0.75


p Value
0.088
0.98
0.032
0.61
0.33
0.32
0.97
na
0.72


95% CI of
0.89
0.27
1.1
0.43
0.32
0.59
0.13
na
0.16


OR Quart 4
5.4
3.6
7.0
4.1
31
4.9
7.4
na
3.6










Tissue-type plasminogen activator

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
8260
6790
8260
8530
8260
16000



Average
8840
9200
8840
10000
8840
14100



Stdev
6580
9070
6580
7870
6580
9330



p (t-test)

0.77

0.40

0.067



Min
0.840
3.93
0.840
448
0.840
2770



Max
35700
44400
35700
33400
35700
24100



n (Samp)
105
60
105
32
105
6



n (Patient)
38
60
38
32
38
6



sCr only



Median
8210
5190
8210
8610
8210
6720



Average
9130
10400
9130
13700
9130
8080



Stdev
6410
12600
6410
12800
6410
4910



p (t-test)

0.47

0.043

0.74



Min
0.840
1800
0.840
211
0.840
4010



Max
35700
44400
35700
33400
35700
14900



n (Samp)
268
18
268
9
268
4



n (Patient)
89
18
89
9
89
4



UO only



Median
8050
7130
8050
7290
8050
4800



Average
9920
8240
9920
8330
9920
10700



Stdev
10100
6740
10100
4990
10100
8960



p (t-test)

0.27

0.36

0.83



Min
0.840
3.93
0.840
508
0.840
2770



Max
70800
32500
70800
25200
70800
24100



n (Samp)
137
52
137
36
137
9



n (Patient)
48
52
48
36
48
9















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.47
0.43
0.47
0.53
0.57
0.50
0.66
0.46
0.52



SE
0.047
0.072
0.047
0.059
0.10
0.054
0.12
0.15
0.10



p
0.58
0.37
0.49
0.59
0.50
0.95
0.19
0.81
0.84



nCohort 1
105
268
137
105
268
137
105
268
137



nCohort 2
60
18
52
32
9
36
6
4
9



Cutoff 1
3850
3480
4250
5650
6570
5130
3850
4960
3850



Sens 1
70%
72%
71%
72%
78%
72%
83%
75%
78%



Spec 1
27%
19%
30%
40%
39%
36%
27%
28%
28%



Cutoff 2
2410
2920
2150
4690
378
4600
3850
3940
2980



Sens 2
80%
83%
81%
81%
89%
81%
83%
100% 
89%



Spec 2
15%
15%
16%
31%
 4%
31%
27%
22%
19%



Cutoff 3
1750
1890
1560
2430
57.5
2550
2410
3940
2410



Sens 3
90%
94%
90%
91%
100% 
92%
100% 
100% 
100% 



Spec 3
12%
10%
13%
15%
 4%
18%
15%
22%
18%



Cutoff 4
11600
11500
11600
11600
11500
11600
11600
11500
11600



Sens 4
27%
33%
21%
25%
44%
22%
50%
25%
33%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
13100
13300
13600
13100
13300
13600
13100
13300
13600



Sens 5
17%
17%
15%
19%
33%
11%
50%
25%
33%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
16600
17000
20800
16600
17000
20800
16600
17000
20800



Sens 6
12%
11%
 6%
16%
33%
 3%
50%
 0%
22%



Spec 6
90%
90%
91%
90%
90%
91%
90%
90%
91%



OR Quart 2
1.2
0.75
2.2
2.4
1.0
2.7
0.96
1.0
1.5



p Value
0.76
0.71
0.094
0.15
1.0
0.075
0.98
1.0
0.67



95% CI of
0.46
0.16
0.87
0.73
0.14
0.91
0.057
0.061
0.24



OR Quart 2
2.9
3.5
5.7
8.0
7.3
7.9
16
16
9.6



OR Quart 3
1.4
0.74
1.7
2.4
1.0
2.1
0.96
1.0
0.49



p Value
0.44
0.70
0.31
0.15
1.0
0.18
0.98
1.0
0.56



95% CI of
0.58
0.16
0.63
0.73
0.14
0.70
0.057
0.061
0.042



OR Quart 3
3.5
3.4
4.4
8.0
7.3
6.4
16
16
5.6



OR Quart 4
1.6
2.2
1.8
1.4
1.5
0.97
3.1
1.0
1.5



p Value
0.32
0.23
0.21
0.56
0.66
0.97
0.34
1.0
0.67



95% CI of
0.64
0.62
0.71
0.41
0.24
0.29
0.30
0.061
0.24



OR Quart 4
3.9
7.5
4.8
5.1
9.3
3.3
32
16
9.6











Glial cell line-derived neurotrophic factor

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
0.00484
0.00484
0.00484
0.137
0.00484
0.00460



Average
7.01
0.319
7.01
0.317
7.01
0.160



Stdev
36.3
0.696
36.3
0.450
36.3
0.467



p (t-test)

0.49

0.37

0.58



Min
0.00460
0.00460
0.00460
0.00460
0.00460
0.00460



Max
260
2.46
260
1.85
260
1.41



n (Samp)
54
14
54
24
54
9



n (Patient)
53
14
53
24
53
9



sCr only



Median
0.00484
0.00484
0.00484
0.0396
0.00484
0.00460



Average
3.89
0.0698
3.89
0.0396
3.89
0.00460



Stdev
25.5
0.113
25.5
0.0495
25.5
0



p (t-test)

0.80

0.83

0.79



Min
0.00460
0.00460
0.00460
0.00460
0.00460
0.00460



Max
260
0.200
260
0.0746
260
0.00460



n (Samp)
111
3
111
2
111
3



n (Patient)
93
3
93
2
93
3



UO only



Median
0.00484
0.00484
0.00484
0.200
0.00484
0.00484



Average
7.85
0.484
7.85
0.325
7.85
0.316



Stdev
38.4
0.815
38.4
0.442
38.4
0.618



p (t-test)

0.51

0.33

0.56



Min
0.00460
0.00460
0.00460
0.00460
0.00460
0.00460



Max
260
2.46
260
1.85
260
1.41



n (Samp)
48
12
48
25
48
9



n (Patient)
44
12
44
25
44
9















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.47
0.41
0.52
0.53
0.36
0.55
0.35
0.16
0.42



SE
0.088
0.18
0.095
0.072
0.21
0.072
0.11
0.14
0.11



p
0.77
0.59
0.83
0.66
0.51
0.53
0.15
0.017
0.48



nCohort 1
54
111
48
54
111
48
54
111
48



nCohort 2
14
3
12
24
2
25
9
3
9



Cutoff 1
0.00460
0
0.00460
0.00460
0
0.00460
0
0
0



Sens 1
71%
100% 
75%
71%
100% 
72%
100% 
100% 
100% 



Spec 1
35%
 0%
35%
35%
 0%
35%
 0%
 0%
 0%



Cutoff 2
0
0
0
0
0
0
0
0
0



Sens 2
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 



Spec 2
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%



Cutoff 3
0
0
0
0
0
0
0
0
0



Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 



Spec 3
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%



Cutoff 4
0.200
0.519
0.200
0.200
0.519
0.200
0.200
0.519
0.200



Sens 4
21%
 0%
33%
33%
 0%
36%
11%
 0%
22%



Spec 4
70%
74%
71%
70%
74%
71%
70%
74%
71%



Cutoff 5
0.652
0.652
0.652
0.652
0.652
0.652
0.652
0.652
0.652



Sens 5
14%
 0%
25%
 8%
 0%
 8%
11%
 0%
22%



Spec 5
81%
80%
81%
81%
80%
81%
81%
80%
81%



Cutoff 6
3.58
2.46
9.59
3.58
2.46
9.59
3.58
2.46
9.59



Sens 6
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%



Spec 6
91%
93%
92%
91%
93%
92%
91%
93%
92%



OR Quart 2
0.29
>1.1
1.5
0.30
>1.1
0.31
2.1
>0
1.1



p Value
0.31
<0.96
0.67
0.13
<0.96
0.15
0.55
<na
0.94



95% CI of
0.027
>0.064
0.26
0.065
>0.064
0.066
0.17
>na
0.13



OR Quart 2
3.1
na
8.0
1.4
na
1.5
26
na
8.9



OR Quart 3
5.2
>1.0
0.29
1.0
>0
1.0
5.0
>1.0
3.6



p Value
0.038
<0.98
0.30
1.0
<na
1.0
0.17
<0.98
0.17



95% CI of
1.1
>0.062
0.026
0.27
>na
0.26
0.49
>0.062
0.57



OR Quart 3
25
na
3.1
3.7
na
3.8
51
na
23



OR Quart 4
0.29
>1.1
1.5
0.92
>1.1
1.1
2.3
>2.2
0



p Value
0.31
<0.96
0.67
0.90
<0.96
0.84
0.51
<0.52
na



95% CI of
0.027
>0.064
0.26
0.25
>0.064
0.31
0.19
>0.19
na



OR Quart 4
3.1
na
8.0
3.4
na
4.3
28
na
na











Protein S100-B

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
0.134
3.32
0.134
3.32
0.134
12.9



Average
15.7
8.00
15.7
12.3
15.7
36.2



Stdev
51.2
11.3
51.2
24.9
51.2
60.0



p (t-test)

0.58

0.76

0.28



Min
0.0774
0.0774
0.0774
0.0774
0.0774
0.0774



Max
368
33.9
368
121
368
184



n (Samp)
54
14
54
24
54
9



n (Patient)
53
14
53
24
53
9



sCr only



Median
0.134
9.52
0.134
11.7
0.134
5.77



Average
16.8
7.20
16.8
11.7
16.8
6.26



Stdev
45.8
6.24
45.8
16.4
45.8
6.39



p (t-test)

0.72

0.88

0.69



Min
0.0774
0.134
0.0774
0.134
0.0774
0.134



Max
368
11.9
368
23.3
368
12.9



n (Samp)
111
3
111
2
111
3



n (Patient)
93
3
93
2
93
3



UO only



Median
0.134
3.32
0.134
3.32
0.134
22.1



Average
17.0
7.81
17.0
12.3
17.0
38.3



Stdev
54.0
12.1
54.0
24.4
54.0
59.4



p (t-test)

0.56

0.68

0.29



Min
0.0774
0.0774
0.0774
0.0774
0.0774
0.0774



Max
368
33.9
368
121
368
184



n (Samp)
48
12
48
25
48
9



n (Patient)
44
12
44
25
44
9















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.50
0.58
0.46
0.55
0.59
0.54
0.63
0.56
0.63



SE
0.087
0.18
0.095
0.072
0.21
0.072
0.11
0.17
0.11



p
0.96
0.66
0.70
0.45
0.66
0.55
0.24
0.72
0.21



nCohort 1
54
111
48
54
111
48
54
111
48



nCohort 2
14
3
12
24
2
25
9
3
9



Cutoff 1
0.0774
0.0774
0
0.0774
0.0774
0.0774
0.0774
0.0774
0.0774



Sens 1
71%
100% 
100% 
83%
100% 
84%
78%
100% 
78%



Spec 1
22%
23%
 0%
22%
23%
21%
22%
23%
21%



Cutoff 2
0
0.0774
0
0.0774
0.0774
0.0774
0
0.0774
0



Sens 2
100% 
100% 
100% 
83%
100% 
84%
100% 
100% 
100% 



Spec 2
 0%
23%
 0%
22%
23%
21%
 0%
23%
 0%



Cutoff 3
0
0.0774
0
0
0.0774
0
0
0.0774
0



Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 



Spec 3
 0%
23%
 0%
 0%
23%
 0%
 0%
23%
 0%



Cutoff 4
9.52
12.9
9.52
9.52
12.9
9.52
9.52
12.9
9.52



Sens 4
29%
 0%
25%
33%
50%
36%
56%
 0%
56%



Spec 4
74%
72%
71%
74%
72%
71%
74%
72%
71%



Cutoff 5
22.1
22.1
18.4
22.1
22.1
18.4
22.1
22.1
18.4



Sens 5
14%
 0%
17%
17%
50%
16%
33%
 0%
56%



Spec 5
81%
81%
81%
81%
81%
81%
81%
81%
81%



Cutoff 6
33.9
33.9
33.9
33.9
33.9
33.9
33.9
33.9
33.9



Sens 6
 0%
 0%
 0%
 4%
 0%
 4%
22%
 0%
22%



Spec 6
91%
91%
92%
91%
91%
92%
91%
91%
92%



OR Quart 2
0.43
0
1.5
0.93
>0
1.0
0.43
0
0.46



p Value
0.38
na
0.67
0.93
<na
1.0
0.51
na
0.55



95% CI of
0.068
na
0.26
0.22
>na
0.23
0.035
na
0.037



OR Quart 2
2.8
na
8.0
3.9
na
4.3
5.3
na
5.8



OR Quart 3
1.4
2.1
0.29
1.6
>1.0
1.7
0.93
2.1
0.46



p Value
0.70
0.56
0.30
0.49
<0.98
0.48
0.94
0.56
0.55



95% CI of
0.29
0.18
0.026
0.41
>0.062
0.41
0.11
0.18
0.037



OR Quart 3
6.3
24
3.1
6.5
na
6.7
7.6
24
5.8



OR Quart 4
0.70
0
1.5
1.5
>1.0
1.9
2.2
0
3.0



p Value
0.67
na
0.67
0.56
<1.0
0.36
0.42
na
0.24



95% CI of
0.13
na
0.26
0.38
>0.060
0.48
0.33
na
0.48



OR Quart 4
3.7
na
8.0
6.0
na
7.5
14
na
19











Resistin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
12300
20000
12300
17900
12300
11000



Average
17400
25200
17400
21900
17400
13500



Stdev
16700
24100
16700
15500
16700
9050



p (t-test)

0.0051

0.082

0.37



Min
1550
2630
1550
2120
1550
2860



Max
118000
150000
118000
60100
118000
35100



n(Samp)
158
73
158
55
158
15



n (Patient)
88
73
88
55
88
15



sCr only



Median
14800
23300
14800
19300
14800
17300



Average
19500
32700
19500
21400
19500
19600



Stdev
16900
32000
16900
16800
16900
10100



p (t-test)

0.0014

0.72

0.99



Min
1550
3100
1550
2120
1550
9360



Max
135000
150000
135000
56400
135000
35600



n (Samp)
378
20
378
11
378
7



n (Patient)
175
20
175
11
175
7



UO only



Median
13900
19000
13900
21000
13900
12100



Average
20400
24800
20400
22900
20400
20300



Stdev
17800
24800
17800
15400
17800
17800



p (t-test)

0.13

0.34

0.97



Min
1620
2630
1620
3300
1620
2860



Max
118000
150000
118000
60100
118000
66600



n(Samp)
184
64
184
61
184
18



n (Patient)
89
64
89
61
89
18















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.63
0.66
0.56
0.60
0.54
0.57
0. 45
0.57
0.49


SE
0.041
0.068
0.042
0.046
0.090
0.043
0.080
0.11
0.072


p
0.0018
0.018
0.17
0.025
0.65
0.12
0.52
0.55
0.91


nCohort 1
158
378
184
158
378
184
158
378
184


nCohort 2
73
20
64
55
11
61
15
7
18


Cutoff 1
11000
16600
11000
11100
9630
12500
8790
11900
9630


Sens 1
71%
70%
70%
71%
73%
70%
73%
71%
72%


Spec 1
43%
56%
38%
45%
32%
47%
33%
41%
32%


Cutoff 2
7700
12500
7520
7600
9520
7700
7230
11100
7230


Sens 2
81%
80%
81%
80%
82%
80%
80%
86%
83%


Spec 2
23%
43%
18%
23%
32%
19%
22%
37%
18%


Cutoff 3
5700
7730
5710
4850
9390
5400
3670
9340
3670


Sens 3
90%
90%
91%
91%
91%
90%
93%
100% 
94%


Spec 3
16%
23%
14%
13%
31%
12%
 8%
30%
 7%


Cutoff 4
18100
24100
24100
18100
24100
24100
18100
24100
24100


Sens 4
56%
45%
36%
49%
18%
38%
27%
29%
28%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
26600
30700
32400
26600
30700
32400
26600
30700
32400


Sens 5
30%
40%
25%
35%
18%
25%
 7%
14%
22%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
33400
37700
44000
33400
37700
44000
33400
37700
44000


Sens 6
25%
30%
 8%
24%
18%
13%
 7%
 0%
11%


Spec 6
91%
90%
90%
91%
90%
90%
91%
90%
90%


OR Quart 2
0.53
0.65
0.82
0.70
4.1
1.0
0.49
>3.1
1.0


p Value
0.17
0.64
0.66
0.47
0.21
1.0
0.42
<0.33
0.98


95% CI of
0.22
0.11
0.35
0.27
0.45
0.42
0.085
>0.32
0.24


OR Quart 2
1.3
4.0
2.0
1.8
38
2.4
2.8
na
4.3


OR Quart 3
1.5
2.4
1.5
1.3
4.1
1.4
1.3
>2.0
1.6


p Value
0.35
0.21
0.31
0.50
0.21
0.40
0.70
<0.56
0.51


95% CI of
0.66
0.61
0.68
0.56
0.45
0.62
0.33
>0.18
0.41


OR Quart 3
3.2
9.7
3.4
3.2
38
3.3
5.3
na
5.9


OR Quart 4
2.1
2.8
1.5
1.9
2.0
1.5
1.0
>2.0
1.0


p Value
0.064
0.14
0.31
0.16
0.57
0.33
0.97
<0.57
0.98


95% CI of
0.96
0.72
0.68
0.79
0.18
0.66
0.24
>0.18
0.24


OR Quart 4
4.5
11
3.4
4.3
22
3.4
4.4
na
4.3










Parathyroid hormone

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
24.9
34.0
24.9
45.5
24.9
32.0



Average
43.0
49.8
43.0
59.0
43.0
46.4



Stdev
58.4
54.5
58.4
52.9
58.4
38.7



p (t-test)

0.40

0.11

0.80



Min
5.71
7.35
5.71
2.59
5.71
3.51



Max
485
302
485
291
485
158



n (Samp)
130
77
130
44
130
20



n (Patient)
59
77
59
44
59
20



sCr only



Median
30.2
47.8
30.2
55.9
30.2
29.1



Average
46.2
64.0
46.2
75.0
46.2
39.2



Stdev
58.0
68.4
58.0
67.8
58.0
32.1



p (t-test)

0.16

0.063

0.71



Min
2.59
11.0
2.59
12.0
2.59
3.51



Max
506
298
506
291
506
96.5



n(Samp)
341
23
341
15
341
10



n (Patient)
138
23
138
15
138
10



UO only



Median
29.2
33.5
29.2
42.4
29.2
30.7



Average
51.2
46.1
51.2
50.8
51.2
43.8



Stdev
66.7
48.6
66.7
39.1
66.7
39.3



p (t-test)

0.57

0.97

0.65



Min
4.99
7.35
4.99
2.59
4.99
10.4



Max
485
302
485
189
485
158



n(Samp)
159
66
159
50
159
18



n (Patient)
65
66
65
50
65
18















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.59
0.62
0.54
0.67
0.72
0.59
0.58
0.48
0.52



SE
0.041
0.064
0.043
0.049
0.076
0.047
0.071
0.094
0.073



p
0.029
0.052
0.32
4.2E−4
0.0030
0.057
0.23
0.82
0.78



nCohort 1
130
341
159
130
341
159
130
341
159



nCohort 2
77
23
66
44
15
50
20
10
18



Cutoff 1
23.7
25.1
23.7
32.9
40.7
26.8
29.3
16.8
22.4



Sens 1
70%
74%
71%
70%
73%
70%
70%
70%
72%



Spec 1
48%
43%
45%
65%
67%
48%
55%
21%
42%



Cutoff 2
18.8
19.8
18.8
26.3
37.6
19.3
17.9
14.8
17.2



Sens 2
82%
83%
80%
82%
80%
80%
80%
80%
83%



Spec 2
27%
28%
26%
52%
65%
27%
24%
16%
21%



Cutoff 3
14.1
19.0
14.1
15.7
14.4
16.6
11.9
7.57
11.6



Sens 3
91%
91%
91%
91%
93%
90%
90%
90%
94%



Spec 3
16%
27%
16%
19%
15%
20%
10%
 4%
 9%



Cutoff 4
36.7
42.7
43.9
36.7
42.7
43.9
36.7
42.7
43.9



Sens 4
47%
52%
30%
61%
67%
46%
45%
40%
28%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
49.0
55.6
63.4
49.0
55.6
63.4
49.0
55.6
63.4



Sens 5
30%
48%
17%
39%
53%
24%
35%
30%
17%



Spec 5
80%
80%
81%
80%
80%
81%
80%
80%
81%



Cutoff 6
85.3
88.8
121
85.3
88.8
121
85.3
88.8
121



Sens 6
 8%
13%
 6%
18%
27%
 8%
10%
10%
11%



Spec 6
90%
90%
91%
90%
90%
91%
90%
90%
91%



OR Quart 2
0.89
8.7
1.1
0.32
0
0.65
0.17
0.24
0.37



p Value
0.78
0.044
0.83
0.11
na
0.43
0.12
0.21
0.25



95% CI of
0.38
1.1
0.47
0.079
na
0.23
0.019
0.026
0.068



OR Quart 2
2.1
71
2.6
1.3
na
1.9
1.6
2.2
2.0



OR Quart 3
1.6
3.1
1.9
2.6
1.5
2.4
1.5
0.24
1.2



p Value
0.25
0.34
0.11
0.058
0.65
0.052
0.53
0.21
0.75



95% CI of
0.72
0.31
0.86
0.97
0.25
0.99
0.43
0.026
0.35



OR Quart 3
3.6
30
4.4
6.9
9.3
5.9
5.2
2.2
4.4



OR Quart 4
1.9
12
1.1
2.8
5.5
1.5
1.4
1.0
0.98



p Value
0.13
0.017
0.87
0.042
0.031
0.38
0.56
0.99
0.97



95% CI of
0.84
1.6
0.46
1.0
1.2
0.60
0.41
0.24
0.26



OR Quart 4
4.2
98
2.5
7.3
26
3.8
5.0
4.2
3.6











Serum albumin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
1.89E7
1.84E7
1.89E7
1.89E7
1.89E7
1.80E7



Average
1.90E7
1.83E7
1.90E7
1.82E7
1.90E7
1.88E7



Stdev
6630000
5710000
6630000
5860000
6630000
4110000



p (t-test)

0.75

0.62

0.94



Min
6690000
6640000
6690000
5860000
6690000
1.08E7



Max
3.44E7
2.60E7
3.44E7
2.82E7
3.44E7
2.64E7



n (Samp)
50
12
50
23
50
9



n (Patient)
49
12
49
23
49
9



sCr only



Median
1.90E7
1.83E7
1.90E7
2.26E7
1.90E7
1.75E7



Average
1.90E7
1.83E7
1.90E7
2.26E7
1.90E7
1.83E7



Stdev
6430000
132000
6430000
3150000
6430000
1490000



p (t-test)

0.86

0.44

0.85



Min
5860000
1.82E7
5860000
2.04E7
5860000
1.74E7



Max
3.44E7
1.84E7
3.44E7
2.48E7
3.44E7
2.00E7



n (Samp)
106
2
106
2
106
3



n (Patient)
88
2
88
2
88
3



UO only



Median
1.88E7
1.85E7
1.88E7
2.04E7
1.88E7
1.80E7



Average
1.91E7
1.83E7
1.91E7
1.87E7
1.91E7
2.02E7



Stdev
6630000
5990000
6630000
5950000
6630000
6240000



p (t-test)

0.73

0.80

0.64



Min
6690000
6640000
6690000
5860000
6690000
1.08E7



Max
3.44E7
2.60E7
3.44E7
2.82E7
3.44E7
3.28E7



n (Samp)
44
11
44
25
44
9



n (Patient)
40
11
40
25
40
9















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.49
0.45
0.49
0.48
0.68
0.51
0.50
0.44
0.54


SE
0.094
0.21
0.098
0.074
0.21
0.073
0.11
0.17
0.11


p
0.88
0.81
0.96
0.79
0.40
0.88
0.97
0.73
0.70


nCohort 1
50
106
44
50
106
44
50
106
44


nCohort 2
12
2
11
23
2
25
9
3
9


Cutoff 1
1.61E7
1.80E7
1.61E7
1.52E7
1.98E7
1.68E7
1.76E7
1.74E7
1.75E7


Sens 1
75%
100% 
73%
74%
100% 
72%
78%
100% 
78%


Spec 1
34%
44%
34%
32%
54%
39%
44%
39%
43%


Cutoff 2
1.52E7
1.80E7
1.53E7
1.35E7
1.98E7
1.42E7
1.74E7
1.74E7
1.74E7


Sens 2
83%
100% 
82%
83%
100% 
80%
89%
100% 
89%


Spec 2
32%
44%
32%
30%
54%
27%
40%
39%
41%


Cutoff 3
8940000
1.80E7
6690000
7090000
1.98E7
7090000
1.06E7
1.74E7
1.06E7


Sens 3
92%
100% 
91%
91%
100% 
92%
100% 
100% 
100% 


Spec 3
 4%
44%
 2%
 2%
54%
 2%
14%
39%
11%


Cutoff 4
2.18E7
2.23E7
2.18E7
2.18E7
2.23E7
2.18E7
2.18E7
2.23E7
2.18E7


Sens 4
33%
 0%
36%
26%
50%
28%
11%
 0%
22%


Spec 4
70%
71%
70%
70%
71%
70%
70%
71%
70%


Cutoff 5
2.36E7
2.37E7
2.36E7
2.36E7
2.37E7
2.36E7
2.36E7
2.37E7
2.36E7


Sens 5
17%
 0%
18%
22%
50%
24%
11%
 0%
22%


Spec 5
80%
80%
82%
80%
80%
82%
80%
80%
82%


Cutoff 6
2.66E7
2.69E7
2.66E7
2.66E7
2.69E7
2.66E7
2.66E7
2.69E7
2.66E7


Sens 6
 0%
 0%
 0%
 4%
 0%
 8%
 0%
 0%
11%


Spec 6
90%
91%
91%
90%
91%
91%
90%
91%
91%


OR Quart 2
0.67
>0
0.61
1.1
>0
1.3
4.7
>1.1
5.3


p Value
0.68
<na
0.62
0.91
<na
0.71
0.19
<0.96
0.16


95% CI of
0.095
>na
0.085
0.27
>na
0.31
0.46
>0.064
0.51


OR Quart 2
4.7
na
4.4
4.3
na
5.5
49
na
56


OR Quart 3
2.0
>2.2
1.5
1.4
>1.0
1.7
3.2
>2.2
2.2


p Value
0.42
<0.54
0.66
0.64
<0.98
0.47
0.33
<0.52
0.55


95% CI of
0.38
>0.18
0.26
0.36
>0.062
0.41
0.30
>0.19
0.17


OR Quart 3
10
na
8.2
5.3
na
7.0
36
na
28


OR Quart 4
0.67
>0
0.67
0.62
>1.0
1.5
0.93
>0
2.0


p Value
0.68
<na
0.69
0.52
<0.98
0.56
0.96
<na
0.59


95% CI of
0.095
>na
0.093
0.14
>0.062
0.37
0.053
>na
0.16


OR Quart 4
4.7
na
4.8
2.7
na
6.3
16
na
25










Cortisol

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
78.1
95.9
78.1
131
78.1
159



Average
175
224
175
244
175
431



Stdev
279
330
279
405
279
581



p (t-test)

0.31

0.28

0.044



Min
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5



Max
1200
1500
1200
1500
1200
1500



n (Samp)
105
61
105
32
105
6



n (Patient)
38
61
38
32
38
6



sCr only



Median
97.5
113
97.5
67.4
97.5
187



Average
203
238
203
251
203
163



Stdev
308
342
308
430
308
70.6



p (t-test)

0.64

0.65

0.79



Min
1.22E−5
17.1
1.22E−5
4.83
1.22E−5
60.5



Max
1500
1330
1500
1350
1500
218



n (Samp)
269
18
269
9
269
4



n (Patient)
89
18
89
9
89
4



UO only



Median
74.2
112
74.2
140
74.2
151



Average
172
236
172
273
172
338



Stdev
292
314
292
398
292
483



p (t-test)

0.19

0.089

0.12



Min
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5



Max
1500
1500
1500
1500
1500
1500



n (Samp)
137
53
137
36
137
9



n (Patient)
48
53
48
36
48
9















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.59
0.55
0.62
0.60
0.49
0.67
0.64
0.65
0.66



SE
0.046
0.072
0.047
0.059
0.099
0.054
0.13
0.15
0.10



p
0.059
0.49
0.0079
0.087
0.88
0.0020
0.25
0.32
0.12



nCohort 1
105
269
137
105
269
137
105
269
137



nCohort 2
61
18
53
32
9
36
6
4
9



Cutoff 1
57.7
51.5
75.5
67.4
37.9
97.5
61.6
173
81.6



Sens 1
70%
72%
72%
72%
78%
72%
83%
75%
78%



Spec 1
44%
30%
51%
46%
26%
58%
45%
72%
54%



Cutoff 2
40.4
33.7
54.1
36.8
37.6
71.2
61.6
57.7
61.6



Sens 2
80%
83%
81%
81%
89%
81%
83%
100% 
89%



Spec 2
37%
25%
42%
36%
26%
47%
45%
32%
44%



Cutoff 3
17.0
31.5
16.5
17.9
4.13
18.5
0
57.7
0



Sens 3
90%
94%
91%
91%
100% 
92%
100% 
100% 
100% 



Spec 3
23%
23%
20%
25%
 5%
23%
 0%
32%
 0%



Cutoff 4
135
167
128
135
167
128
135
167
128



Sens 4
38%
39%
47%
47%
33%
64%
67%
75%
56%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
212
226
194
212
226
194
212
226
194



Sens 5
23%
28%
34%
19%
22%
28%
33%
 0%
33%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
474
675
446
474
675
446
474
675
446



Sens 6
11%
11%
13%
 9%
11%
11%
33%
 0%
22%



Spec 6
90%
90%
91%
90%
90%
91%
90%
90%
91%



OR Quart 2
2.0
0.99
1.3
1.2
0.33
1.3
0.96
>1.0
0.97



p Value
0.17
0.98
0.64
0.74
0.34
0.73
0.98
<0.99
0.98



95% CI of
0.75
0.24
0.46
0.34
0.033
0.32
0.057
>0.062
0.058



OR Quart 2
5.2
4.1
3.6
4.5
3.2
5.1
16
na
16



OR Quart 3
3.4
0.99
2.8
3.6
1.4
4.7
2.0
>1.0
2.1



p Value
0.013
0.98
0.039
0.033
0.70
0.012
0.58
<0.99
0.56



95% CI of
1.3
0.24
1.1
1.1
0.29
1.4
0.17
>0.062
0.18



OR Quart 3
8.8
4.1
7.3
12
6.3
16
23
na
24



OR Quart 4
2.4
1.5
2.9
1.7
0.33
4.1
2.0
>2.0
5.5



p Value
0.072
0.53
0.028
0.39
0.34
0.023
0.58
<0.57
0.13



95% CI of
0.92
0.41
1.1
0.50
0.033
1.2
0.17
>0.18
0.61



OR Quart 4
6.3
5.6
7.6
5.9
3.2
14
23
na
49

















TABLE 6





Comparison of marker levels in EDTA samples collected from Cohort 1 (patients that


did not progress beyond RIFLE stage 0 or R) and in EDTA samples collected from subjects


at 0, 24 hours, and 48 hours prior to reaching stage I or F in Cohort 2.







Serum amyloid A protein

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
96800
893000
96800
48300
96800
94300



Average
669000
952000
669000
503000
669000
635000



Stdev
795000
947000
795000
706000
795000
786000



p (t-test)

0.081

0.32

0.87



Min
16.4
657
16.4
426
16.4
610



Max
2630000
2630000
2630000
2630000
2630000
2630000



n (Samp)
246
28
246
25
246
15



n (Patient)
90
28
90
25
90
15



sCr only



Median
75300
458000
75300
893000
75300
460000



Average
704000
458000
704000
753000
704000
570000



Stdev
850000
614000
850000
668000
850000
656000



p (t-test)

0.68

0.92

0.75



Min
16.4
24000
16.4
25500
16.4
22000



Max
2630000
893000
2630000
1340000
2630000
1340000



n (Samp)
355
2
355
3
355
4



n (Patient)
116
2
116
3
116
4



UO only



Median
95700
893000
95700
50100
95700
60700



Average
667000
1050000
667000
486000
667000
584000



Stdev
792000
980000
792000
698000
792000
790000



p (t-test)

0.020

0.26

0.70



Min
16.4
657
16.4
426
16.4
610



Max
2630000
2630000
2630000
2630000
2630000
2630000



n (Samp)
251
28
251
26
251
14



n (Patient)
91
28
91
26
91
14















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.57
0.42
0.60
0.44
0.56
0.44
0.44
0.48
0.41


SE
0.059
0.21
0.059
0.062
0.17
0.061
0.079
0.15
0.082


p
0.24
0.72
0.11
0.36
0.74
0.35
0.46
0.89
0.29


nCohort 1
246
355
251
246
355
251
246
355
251


nCohort 2
28
2
28
25
3
26
15
4
14


Cutoff 1
46900
23700
51400
21200
25300
21200
21200
27200
21200


Sens 1
71%
100% 
71%
72%
100% 
73%
73%
75%
71%


Spec 1
46%
23%
47%
18%
24%
18%
18%
28%
18%


Cutoff 2
20200
23700
20200
17100
25300
17100
17400
21200
4190


Sens 2
82%
100% 
82%
80%
100% 
81%
80%
100% 
86%


Spec 2
17%
23%
16%
12%
24%
12%
13%
21%
 2%


Cutoff 3
6720
23700
6720
6720
25300
6720
2540
21200
2540


Sens 3
93%
100% 
93%
92%
100% 
92%
93%
100% 
93%


Spec 3
 3%
23%
 3%
 3%
24%
 3%
 1%
21%
 1%


Cutoff 4
893000
893000
893000
893000
893000
893000
893000
893000
893000


Sens 4
39%
 0%
43%
24%
33%
23%
27%
25%
21%


Spec 4
74%
72%
73%
74%
72%
73%
74%
72%
73%


Cutoff 5
1340000
1340000
1340000
1340000
1340000
1340000
1340000
1340000
1340000


Sens 5
18%
 0%
21%
 4%
 0%
 4%
 7%
 0%
 7%


Spec 5
91%
89%
92%
91%
89%
92%
91%
89%
92%


Cutoff 6
1340000
2630000
1340000
1340000
2630000
1340000
1340000
2630000
1340000


Sens 6
18%
 0%
21%
 4%
 0%
 4%
 7%
 0%
 7%


Spec 6
91%
100% 
92%
91%
100% 
92%
91%
100% 
92%


OR Quart 2
0.54
>1.0
0.64
0.65
0
0.83
0.75
1.0
2.7


p Value
0.34
<0.99
0.50
0.51
na
0.77
0.71
1.0
0.25


95% CI of
0.15
>0.063
0.17
0.17
na
0.24
0.16
0.062
0.50


OR Quart 2
1.9
na
2.4
2.4
na
2.9
3.5
16
14


OR Quart 3
1.5
>0
1.5
1.2
1.0
1.2
0.49
1.0
0.50


p Value
0.44
<na
0.43
0.77
1.0
0.75
0.42
1.0
0.58


95% CI of
0.54
>na
0.52
0.38
0.062
0.38
0.087
0.062
0.044


OR Quart 3
4.2
na
4.6
3.7
16
3.8
2.8
16
5.7


OR Quart 4
0.98
>1.0
1.5
1.4
0.99
1.4
1.6
1.0
3.2


p Value
0.98
<0.99
0.43
0.55
0.99
0.56
0.50
0.99
0.16


95% CI of
0.33
>0.063
0.52
0.46
0.061
0.46
0.42
0.062
0.63


OR Quart 4
3.0
na
4.6
4.3
16
4.3
5.9
16
17










Tissue-type plasminogen activator

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
7630
7430
7630
7200
7630
8090



Average
9330
8860
9330
8700
9330
9330



Stdev
8320
5820
8320
7180
8320
7150



p (t-test)

0.77

0.72

1.00



Min
0.840
1140
0.840
1180
0.840
1070



Max
70800
24000
70800
34200
70800
21600



n (Samp)
246
28
246
25
246
15



n (Patient)
90
28
90
25
90
15



sCr only



Median
8090
5910
8090
7370
8090
5120



Average
9500
5910
9500
6260
9500
4330



Stdev
7860
5580
7860
2760
7860
2870



p (t-test)

0.52

0.48

0.19



Min
0.840
1960
0.840
3110
0.840
211



Max
70800
9850
70800
8290
70800
6880



n (Samp)
355
2
355
3
355
4



n (Patient)
116
2
116
3
116
4



UO only



Median
7520
7960
7520
7040
7520
8180



Average
9250
9120
9250
8430
9250
9640



Stdev
8250
5660
8250
7170
8250
7320



p (t-test)

0.93

0.63

0.86



Min
0.840
1140
0.840
1180
0.840
1070



Max
70800
24000
70800
34200
70800
21600



n (Samp)
251
28
251
26
251
14



n (Patient)
91
28
91
26
91
14















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.51
0.36
0.53
0.48
0.39
0.47
0.50
0.26
0.51



SE
0.058
0.21
0.059
0.061
0.17
0.060
0.077
0.14
0.080



p
0.81
0.50
0.55
0.72
0.52
0.58
0.96
0.10
0.87



nCohort 1
246
355
251
246
355
251
246
355
251



nCohort 2
28
2
28
25
3
26
15
4
14



Cutoff 1
6480
1910
6620
5530
3110
4860
4960
4960
5130



Sens 1
71%
100% 
71%
72%
100% 
73%
73%
75%
71%



Spec 1
43%
10%
45%
37%
16%
28%
29%
28%
32%



Cutoff 2
3920
1910
5840
4600
3110
3170
3150
57.5
2700



Sens 2
82%
100% 
82%
80%
100% 
81%
80%
100% 
86%



Spec 2
22%
10%
41%
25%
16%
17%
17%
 3%
14%



Cutoff 3
1860
1910
1860
2410
3110
1710
1970
57.5
1970



Sens 3
93%
100% 
93%
92%
100% 
92%
93%
100% 
93%



Spec 3
11%
10%
11%
13%
16%
10%
12%
 3%
12%



Cutoff 4
11400
11500
11200
11400
11500
11200
11400
11500
11200



Sens 4
25%
 0%
25%
12%
 0%
12%
33%
 0%
36%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
13000
13500
13000
13000
13500
13000
13000
13500
13000



Sens 5
14%
 0%
14%
12%
 0%
12%
27%
 0%
29%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
16800
17600
16800
16800
17600
16800
16800
17600
16800



Sens 6
14%
 0%
14%
 8%
 0%
 8%
27%
 0%
29%



Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%



OR Quart 2
1.4
>1.0
1.7
2.9
>1.0
3.4
1.0
>0
0.48



p Value
0.59
<0.99
0.40
0.13
<0.99
0.080
0.98
<na
0.41



95% CI of
0.44
>0.063
0.51
0.73
>0.063
0.87
0.24
>na
0.086



OR Quart 2
4.1
na
5.3
11
na
13
4.2
na
2.7



OR Quart 3
1.6
>0
2.1
3.3
>1.0
2.9
0.75
>3.1
1.0



p Value
0.41
<na
0.19
0.083
<0.99
0.12
0.71
<0.33
1.0



95% CI of
0.53
>na
0.69
0.85
>0.062
0.74
0.16
>0.32
0.24



OR Quart 3
4.7
na
6.6
13
na
12
3.5
na
4.2



OR Quart 4
0.81
>1.0
0.98
1.7
>1.0
2.1
1.0
>1.0
0.98



p Value
0.73
<0.99
0.98
0.46
<0.99
0.30
0.98
<0.99
0.98



95% CI of
0.23
>0.063
0.27
0.40
>0.063
0.51
0.24
>0.063
0.24



OR Quart 4
2.8
na
3.6
7.6
na
8.9
4.2
na
4.1











Protein S100-B















24 hr prior to AKI stage

48 hr prior to AKI stage















Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
0.134
5.77
0.134
2.95



Average
15.7
22.9
15.7
4.36



Stdev
43.8
45.9
43.8
5.56



p (t-test)

0.64

0.53



Min
0.0774
0.0774
0.0774
0.134



Max
368
143
368
14.2



n (Samp)
113
9
113
6



n (Patient)
92
9
92
6



UO only



Median
0.134
5.77
0.134
5.77



Average
16.9
22.9
16.9
5.20



Stdev
46.5
45.9
46.5
5.76



p (t-test)

0.71

0.58



Min
0.0774
0.0774
0.0774
0.134



Max
368
143
368
14.2



n (Samp)
99
9
99
5



n (Patient)
77
9
77
5














24 hr prior to AKI stage
48 hr prior to AKI stage
















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.55
nd
0.55
0.51
nd
0.53



SE
0.10
nd
0.10
0.12
nd
0.13



p
0.62
nd
0.65
0.97
nd
0.83



nCohort 1
113
nd
99
113
nd
99



nCohort 2
9
nd
9
6
nd
5



Cutoff 1
0.0774
nd
0.0774
0.0774
nd
0.0774



Sens 1
78%
nd
78%
100% 
nd
100% 



Spec 1
22%
nd
22%
22%
nd
22%



Cutoff 2
0
nd
0
0.0774
nd
0.0774



Sens 2
100% 
nd
100% 
100% 
nd
100% 



Spec 2
 0%
nd
 0%
22%
nd
22%



Cutoff 3
0
nd
0
0.0774
nd
0.0774



Sens 3
100% 
nd
100% 
100% 
nd
100% 



Spec 3
 0%
nd
 0%
22%
nd
22%



Cutoff 4
12.9
nd
12.9
12.9
nd
12.9



Sens 4
33%
nd
33%
17%
nd
20%



Spec 4
73%
nd
73%
73%
nd
73%



Cutoff 5
22.1
nd
22.1
22.1
nd
22.1



Sens 5
22%
nd
22%
 0%
nd
 0%



Spec 5
81%
nd
81%
81%
nd
81%



Cutoff 6
31.8
nd
33.9
31.8
nd
33.9



Sens 6
11%
nd
11%
 0%
nd
 0%



Spec 6
90%
nd
92%
90%
nd
92%



OR Quart 2
0.47
nd
0.48
>3.2
nd
>2.2



p Value
0.54
nd
0.56
<0.32
nd
<0.54



95% CI of
0.040
nd
0.041
>0.32
nd
>0.18



OR Quart 2
5.4
nd
5.6
na
nd
na



OR Quart 3
1.6
nd
1.6
>2.1
nd
>3.4



p Value
0.64
nd
0.64
<0.56
nd
<0.30



95% CI of
0.24
nd
0.24
>0.18
nd
>0.33



OR Quart 3
10
nd
10
na
nd
na



OR Quart 4
1.5
nd
1.6
>1.0
nd
>0



p Value
0.67
nd
0.64
<1.0
nd
<na



95% CI of
0.23
nd
0.24
>0.060
nd
>na



OR Quart 4
9.7
nd
10
na
nd
na











Serum albumin















24 hr prior to AKI stage

48 hr prior to AKI stage















Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
1.90E7
1.74E7
1.90E7
2.07E7



Average
1.95E7
1.64E7
1.95E7
1.99E7



Stdev
6570000
5700000
6570000
3550000



p (t-test)

0.18

0.89



Min
5860000
7090000
5860000
1.45E7



Max
3.44E7
2.36E7
3.44E7
2.48E7



n (Samp)
109
9
109
6



n (Patient)
87
9
87
6



UO only



Median
1.89E7
1.74E7
1.89E7
2.09E7



Average
1.95E7
1.64E7
1.95E7
2.04E7



Stdev
6550000
5700000
6550000
3720000



p (t-test)

0.18

0.77



Min
5860000
7090000
5860000
1.45E7



Max
3.44E7
2.36E7
3.44E7
2.48E7



n (Samp)
95
9
95
5



n (Patient)
72
9
72
5














24 hr prior to AKI stage
48 hr prior to AKI stage
















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.38
nd
0.38
0.53
nd
0.56



SE
0.10
nd
0.10
0.12
nd
0.14



p
0.23
nd
0.24
0.82
nd
0.66



nCohort 1
109
nd
95
109
nd
95



nCohort 2
9
nd
9
6
nd
5



Cutoff 1
1.11E7
nd
1.11E7
1.74E7
nd
2.05E7



Sens 1
78%
nd
78%
83%
nd
80%



Spec 1
13%
nd
13%
35%
nd
58%



Cutoff 2
1.06E7
nd
1.06E7
1.74E7
nd
2.05E7



Sens 2
89%
nd
89%
83%
nd
80%



Spec 2
11%
nd
11%
35%
nd
58%



Cutoff 3
6690000
nd
6690000
1.42E7
nd
1.42E7



Sens 3
100% 
nd
100% 
100% 
nd
100% 



Spec 3
 3%
nd
 3%
24%
nd
22%



Cutoff 4
2.25E7
nd
2.25E7
2.25E7
nd
2.25E7



Sens 4
11%
nd
11%
17%
nd
20%



Spec 4
71%
nd
71%
71%
nd
71%



Cutoff 5
2.58E7
nd
2.42E7
2.58E7
nd
2.42E7



Sens 5
 0%
nd
 0%
 0%
nd
20%



Spec 5
81%
nd
80%
81%
nd
80%



Cutoff 6
2.82E7
nd
2.82E7
2.82E7
nd
2.82E7



Sens 6
 0%
nd
 0%
 0%
nd
 0%



Spec 6
91%
nd
91%
91%
nd
91%



OR Quart 2
3.3
nd
3.3
0.96
nd
0



p Value
0.31
nd
0.32
0.98
nd
na



95% CI of
0.33
nd
0.32
0.057
nd
na



OR Quart 2
34
nd
34
16
nd
na



OR Quart 3
2.1
nd
2.1
3.1
nd
3.3



p Value
0.56
nd
0.56
0.34
nd
0.32



95% CI of
0.18
nd
0.18
0.30
nd
0.32



OR Quart 3
24
nd
25
32
nd
34



OR Quart 4
3.3
nd
3.3
0.96
nd
1.0



p Value
0.31
nd
0.32
0.98
nd
1.0



95% CI of
0.33
nd
0.32
0.057
nd
0.059



OR Quart 4
34
nd
34
16
nd
17











Cortisol

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
92.9
116
92.9
126
92.9
171



Average
205
205
205
235
205
347



Stdev
319
311
319
343
319
418



p (t-test)

0.99

0.65

0.10



Min
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5



Max
1500
1500
1500
1500
1500
1500



n (Samp)
247
28
247
25
247
15



n (Patient)
90
28
90
25
90
15



sCr only



Median
103
154
103
222
103
203



Average
217
154
217
180
217
186



Stdev
324
59.3
324
131
324
109



p (t-test)

0.78

0.84

0.85



Min
1.22E−5
112
1.22E−5
33.2
1.22E−5
37.9



Max
1500
196
1500
284
1500
302



n (Samp)
356
2
356
3
356
4



n (Patient)
116
2
116
3
116
4



UO only



Median
93.9
116
93.9
118
93.9
169



Average
208
209
208
230
208
358



Stdev
327
311
327
337
327
431



p (t-test)

0.99

0.75

0.10



Min
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5
1.22E−5



Max
1500
1500
1500
1500
1500
1500



n (Samp)
252
28
252
26
252
14



n (Patient)
91
28
91
26
91
14















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.53
0.64
0.53
0.59
0.60
0.59
0.68
0.64
0.67



SE
0.059
0.21
0.058
0.062
0.17
0.061
0.078
0.15
0.081



p
0.57
0.51
0.56
0.14
0.55
0.15
0.023
0.35
0.037



nCohort 1
247
356
252
247
356
252
247
356
252



nCohort 2
28
2
28
25
3
26
15
4
14



Cutoff 1
73.7
112
73.7
100
33.0
97.5
151
198
151



Sens 1
71%
100% 
71%
72%
100% 
73%
73%
75%
71%



Spec 1
41%
54%
40%
53%
21%
52%
72%
74%
71%



Cutoff 2
17.1
112
17.1
86.6
33.0
86.6
101
37.6
62.9



Sens 2
82%
100% 
82%
80%
100% 
81%
80%
100% 
86%



Spec 2
15%
54%
15%
48%
21%
47%
53%
23%
34%



Cutoff 3
4.95
112
4.95
31.9
33.0
31.9
41.7
37.6
41.7



Sens 3
93%
100% 
93%
92%
100% 
92%
93%
100% 
93%



Spec 3
 6%
54%
 5%
23%
21%
23%
28%
23%
27%



Cutoff 4
145
168
148
145
168
148
145
168
148



Sens 4
46%
50%
43%
36%
67%
35%
73%
75%
71%



Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%



Cutoff 5
228
253
228
228
253
228
228
253
228



Sens 5
18%
 0%
21%
16%
33%
15%
33%
25%
36%



Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%



Cutoff 6
555
704
555
555
704
555
555
704
555



Sens 6
 7%
 0%
 7%
12%
 0%
12%
20%
 0%
21%



Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%



OR Quart 2
0.98
>0
1.0
1.4
0
1.7
2.0
0
2.0



p Value
0.98
<na
1.0
0.70
na
0.48
0.58
na
0.58



95% CI of
0.30
>na
0.31
0.29
na
0.39
0.18
na
0.18



OR Quart 2
3.2
na
3.3
6.3
na
7.4
23
na
23



OR Quart 3
1.6
>2.0
1.4
4.6
0
4.6
6.5
1.0
6.5



p Value
0.43
<0.56
0.57
0.022
na
0.022
0.087
1.0
0.087



95% CI of
0.52
>0.18
0.45
1.2
na
1.2
0.76
0.062
0.76



OR Quart 3
4.6
na
4.2
17
na
17
56
16
56



OR Quart 4
1.2
>0
1.4
2.1
2.0
2.1
6.4
2.0
5.2



p Value
0.79
<na
0.57
0.31
0.57
0.32
0.090
0.57
0.14



95% CI of
0.37
>na
0.45
0.50
0.18
0.49
0.75
0.18
0.60



OR Quart 4
3.7
na
4.2
8.8
22
8.6
55
23
46

















TABLE 7





Comparison of marker levels in EDTA samples collected within 12


hours of reaching stage R from Cohort 1 (patients that reached, but did


not progress beyond, RIFLE stage R) and from Cohort 2 (patients that


reached RIFLE stage I or F).







Glial cell line-derived neurotrophic factor















sCr or UO

UO only















Cohort 1
Cohort 2
Cohort 1
Cohort 2







Median
0.00484
0.0746
0.00484
0.137



Average
0.544
0.0931
0.663
0.120



Stdev
1.00
0.0886
1.11
0.0970



p(t-test)

0.29

0.35



Min
0.00460
0.00460
0.00460
0.00460



Max
3.58
0.200
3.58
0.200



n (Samp)
23
6
18
4



n (Patient)
23
6
18
4














At Enrollment













sCr or UO
UO only







AUC
0.49
0.53



SE
0.14
0.16



p
0.91
0.87



nCohort 1
23
18



nCohort 2
6
4



Cutoff 1
0
0.00484



Sens 1
100% 
75%



Spec 1
 0%
61%



Cutoff 2
0
0



Sens 2
100% 
100% 



Spec 2
 0%
 0%



Cutoff 3
0
0



Sens 3
100% 
100% 



Spec 3
 0%
 0%



Cutoff 4
0.519
0.652



Sens 4
 0%
 0%



Spec 4
74%
72%



Cutoff 5
1.10
1.56



Sens 5
 0%
 0%



Spec 5
83%
83%



Cutoff 6
2.46
2.46



Sens 6
 0%
 0%



Spec 6
96%
94%



OR Quart 2
>11
0



p Value
<0.070
na



95% CI of
>0.82
na



OR Quart2
na
na



OR Quart 3
>0
6.0



p Value
<na
0.21



95% CI of
>na
0.35



OR Quart 3
na
100



OR Quart 4
>3.2
0



p Value
<0.39
na



95% CI of
>0.23
na



OR Quart 4
na
na











Serum albumin













sCr or UO
UO only












Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
2.08E7
1.97E7
1.87E7
2.06E7


Average
2.08E7
1.81E7
1.92E7
1.74E7


Stdev
7130000
4080000
6470000
5870000


p(t-test)

0.38

0.66


Min
6640000
1.07E7
6640000
1.07E7


Max
3.36E7
2.12E7
3.14E7
2.10E7


n (Samp)
23
6
18
3


n (Patient)
23
6
18
3













At Enrollment













sCr or UO
UO only







AUC
0.38
0.43



SE
0.14
0.19



p
0.39
0.69



nCohort 1
23
18



nCohort 2
6
3



Cutoff 1
1.61E7
1.01E7



Sens 1
83%
100% 



Spec 1
22%
17%



Cutoff 2
1.61E7
1.01E7



Sens 2
83%
100% 



Spec 2
22%
17%



Cutoff 3
1.01E7
1.01E7



Sens 3
100% 
100% 



Spec 3
13%
17%



Cutoff 4
2.37E7
2.23E7



Sens 4
 0%
 0%



Spec 4
74%
72%



Cutoff 5
2.78E7
2.37E7



Sens 5
 0%
 0%



Spec 5
83%
83%



Cutoff 6
3.14E7
2.86E7



Sens 6
 0%
 0%



Spec 6
91%
94%



OR Quart 2
>6.0
>4.0



p Value
<0.17
<0.33



95% CI of
>0.46
>0.25



OR Quart 2
na
na



OR Quart 3
>1.3
>0



p Value
<0.85
<na



95% CI of
>0.069
>na



OR Quart 3
na
na



OR Quart 4
>3.2
>1.5



p Value
<0.39
<0.79



95% CI of
>0.23
>0.071



OR Quart 4
na
na

















TABLE 8





Comparison of the maximum marker levels in EDTA samples


collected from Cohort 1 (patients that did not progress beyond RIFLE stage 0) and the


maximum values in EDTA samples collected from subjects between enrollment and 0, 24


hours, and 48 hours prior to reaching stage F in Cohort 2.







Serum amyloid A protein

















0 hr prior to

24 hr prior to

48 hr prior to




AKI stage

AKI stage

AKI stage
















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
893000
1980000
893000
1340000
893000
1340000



Average
935000
1840000
935000
1680000
935000
1150000



Stdev
900000
914000
900000
868000
900000
933000



p (t-test)

0.013

0.037

0.59



Min
14600
220000
14600
220000
14600
52000



Max
2630000
2630000
2630000
2630000
2630000
2630000



n (Samp)
38
8
38
8
38
6



n (Patient)
38
8
38
8
38
6



sCr only



Median
893000
1340000
893000
1340000
893000
1340000



Average
1140000
1370000
1140000
1370000
1140000
1370000



Stdev
982000
852000
982000
852000
982000
852000



p (t-test)

0.60

0.60

0.60



Min
10900
220000
10900
220000
10900
220000



Max
2630000
2630000
2630000
2630000
2630000
2630000



n (Samp)
89
5
89
5
89
5



n (Patient)
89
5
89
5
89
5



UO only



Median
893000
2630000
893000
1980000
893000
696000



Average
920000
2300000
920000
1980000
920000
696000



Stdev
880000
643000
880000
742000
880000
910000



p (t-test)

0.0035

0.023

0.73



Min
14600
1340000
14600
1340000
14600
52000



Max
2630000
2630000
2630000
2630000
2630000
1340000



n (Samp)
48
4
48
4
48
2



n (Patient)
48
4
48
4
48
2















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.78
0.63
0.88
0.76
0.63
0.83
0.63
0.63
0.52


SE
0.10
0.14
0.11
0.10
0.14
0.13
0.13
0.14
0.21


p
0.0054
0.33
7.8E−4
0.013
0.33
0.0094
0.31
0.33
0.94


nCohort 1
38
89
48
38
89
48
38
89
48


nCohort 2
8
5
4
8
5
4
6
5
2


Cutoff 1
893000
1180000
1340000
893000
1180000
893000
60300
1180000
42100


Sens 1
88%
80%
75%
88%
80%
100% 
83%
80%
100% 


Spec 1
63%
56%
85%
63%
56%
62%
37%
56%
29%


Cutoff 2
893000
1180000
893000
893000
1180000
893000
60300
1180000
42100


Sens 2
88%
80%
100% 
88%
80%
100% 
83%
80%
100% 


Spec 2
63%
56%
62%
63%
56%
62%
37%
56%
29%


Cutoff 3
60300
95700
893000
60300
95700
893000
42100
95700
42100


Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 


Spec 3
37%
31%
62%
37%
31%
62%
29%
31%
29%


Cutoff 4
1340000
1340000
1340000
1340000
1340000
1340000
1340000
1340000
1340000


Sens 4
50%
20%
75%
38%
20%
50%
17%
20%
 0%


Spec 4
84%
75%
85%
84%
75%
85%
84%
75%
85%


Cutoff 5
1340000
2630000
1340000
1340000
2630000
1340000
1340000
2630000
1340000


Sens 5
50%
 0%
75%
38%
 0%
50%
17%
 0%
 0%


Spec 5
84%
100% 
85%
84%
100% 
85%
84%
100% 
85%


Cutoff 6
2630000
2630000
2630000
2630000
2630000
2630000
2630000
2630000
2630000


Sens 6
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%


Spec 6
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 


OR Quart 2
>1.0
>1.0
>0
>1.0
>1.0
>0
>2.4
>1.0
>1.0


p Value
<1.0
<1.0
<na
<1.0
<1.0
<na
<0.49
<1.0
<1.0


95% CI of
>0.055
>0.059
>na
>0.055
>0.059
>na
>0.19
>0.059
>0.056


OR Quart 2
na
na
na
na
na
na
na
na
na


OR Quart 3
>2.4
>3.4
>0
>2.4
>3.4
>1.1
>4.1
>3.4
>0


p Value
<0.49
<0.30
<na
<0.49
<0.30
<0.96
<0.25
<0.30
<na


95% CI of
>0.19
>0.33
>na
>0.19
>0.33
>0.061
>0.36
>0.33
>na


OR Quart 3
na
na
na
na
na
na
na
na
na


OR Quart 4
>7.9
>1.0
>5.8
>7.9
>1.0
>3.9
>1.1
>1.0
>1.0


p Value
<0.085
<1.0
<0.14
<0.085
<1.0
<0.27
<0.95
<1.0
<1.0


95% CI of
>0.75
>0.059
>0.55
>0.75
>0.059
>0.35
>0.060
>0.059
>0.056


OR Quart 4
na
na
na
na
na
na
na
na
na










Tissue-type plasminogen activator

















0 hr prior to

24 hr prior to

48 hr prior to




AKI stage

AKI stage

AKI stage
















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
11400
14400
11400
12800
11400
8460



Average
11400
13300
11400
11900
11400
9780



Stdev
7300
6860
7300
5490
7300
7180



p (t-test)

0.51

0.85

0.61



Min
1750
4010
1750
4010
1750
1960



Max
35700
22900
35700
19000
35700
19000



n (Samp)
38
8
38
8
38
6



n (Patient)
38
8
38
8
38
6



sCr only



Median
11900
12000
11900
12000
11900
12000



Average
12400
11300
12400
11300
12400
11300



Stdev
6750
6790
6750
6790
6750
6790



p (t-test)

0.74

0.74

0.74



Min
1750
4010
1750
4010
1750
4010



Max
35700
19000
35700
19000
35700
19000



n (Samp)
89
5
89
5
89
5



n (Patient)
89
5
89
5
89
5



UO only



Median
10900
13400
10900
11500
10900
3430



Average
13300
13600
13300
10900
13300
3430



Stdev
12500
8090
12500
4820
12500
2090



p (t-test)

0.95

0.71

0.28



Min
1750
4910
1750
4910
1750
1960



Max
70800
22900
70800
15700
70800
4910



n (Samp)
48
4
48
4
48
2



n (Patient)
48
4
48
4
48
2















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.61
0.48
0.59
0.57
0.48
0.53
0.44
0.48
0.10



SE
0.12
0.13
0.16
0.12
0.13
0.15
0.13
0.13
0.15



p
0.35
0.87
0.57
0.55
0.87
0.87
0.66
0.87
0.0085



nCohort 1
38
89
48
38
89
48
38
89
48



nCohort 2
8
5
4
8
5
4
6
5
2



Cutoff 1
8900
4690
8900
8900
4690
8900
3850
4690
1800



Sens 1
75%
80%
75%
75%
80%
75%
83%
80%
100% 



Spec 1
39%
 9%
44%
39%
 9%
44%
11%
 9%
 4%



Cutoff 2
4690
4690
4690
4690
4690
4690
3850
4690
1800



Sens 2
88%
80%
100% 
88%
80%
100% 
83%
80%
100% 



Spec 2
18%
 9%
17%
18%
 9%
17%
11%
 9%
 4%



Cutoff 3
3850
3850
4690
3850
3850
4690
1750
3850
1800



Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 



Spec 3
11%
 6%
17%
11%
 6%
17%
 3%
 6%
 4%



Cutoff 4
13600
13900
13600
13600
13900
13600
13600
13900
13600



Sens 4
50%
40%
50%
50%
40%
50%
33%
40%
 0%



Spec 4
71%
71%
71%
71%
71%
71%
71%
71%
71%



Cutoff 5
15500
16500
16100
15500
16500
16100
15500
16500
16100



Sens 5
50%
40%
50%
38%
40%
 0%
33%
40%
 0%



Spec 5
82%
81%
81%
82%
81%
81%
82%
81%
81%



Cutoff 6
21200
19300
29900
21200
19300
29900
21200
19300
29900



Sens 6
12%
 0%
 0%
 0%
 0%
 0%
 0%
 0%
 0%



Spec 6
92%
91%
92%
92%
91%
92%
92%
91%
92%



OR Quart 2
0.41
0.50
1.0
0.41
0.50
1.0
0.45
0.50
>0



p Value
0.49
0.58
1.0
0.49
0.58
1.0
0.54
0.58
<na



95% CI of
0.032
0.042
0.056
0.032
0.042
0.056
0.035
0.042
>na



OR Quart 2
5.3
5.9
18
5.3
5.9
18
5.8
5.9
na



OR Quart 3
0.45
0
0
1.0
0
1.0
0
0
>0



p Value
0.54
na
na
1.0
na
1.0
na
na
<na



95% CI of
0.035
na
na
0.11
na
0.056
na
na
>na



OR Quart 3
5.8
na
na
8.7
na
18
na
na
na



OR Quart 4
2.2
1.0
2.2
1.5
1.0
1.0
1.7
1.0
>2.6



p Value
0.41
0.96
0.55
0.69
0.96
1.0
0.61
0.96
<0.46



95% CI of
0.32
0.13
0.17
0.20
0.13
0.056
0.22
0.13
>0.21



OR Quart 4
16
8.1
28
11
8.1
18
13
8.1
na











Protein S100-B















0 hr prior to

24 hr prior to




AKI stage

AKI stage














Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
0.134
5.77
0.134
5.77



Average
16.0
42.3
16.0
42.3



Stdev
51.7
68.2
51.7
68.2



p (t-test)

0.40

0.40



Min
0.0774
0.0774
0.0774
0.0774



Max
368
121
368
121



n (Samp)
53
3
53
3



n (Patient)
53
3
53
3



UO only



Median
0.134
2.93
0.134
2.93



Average
17.9
2.93
17.9
2.93



Stdev
56.3
4.03
56.3
4.03



p (t-test)

0.71

0.71



Min
0.0774
0.0774
0.0774
0.0774



Max
368
5.77
368
5.77



n (Samp)
44
2
44
2



n (Patient)
44
2
44
2














0 hr prior to AKI stage
24 hr prior to AKI stage
















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.57
nd
0.35
0.57
nd
0.35



SE
0.18
nd
0.22
0.18
nd
0.22



p
0.70
nd
0.50
0.70
nd
0.50



nCohort 1
53
nd
44
53
nd
44



nCohort 2
3
nd
2
3
nd
2



Cutoff 1
0
nd
0
0
nd
0



Sens 1
100% 
nd
100% 
100% 
nd
100% 



Spec 1
 0%
nd
 0%
 0%
nd
 0%



Cutoff 2
0
nd
0
0
nd
0



Sens 2
100% 
nd
100% 
100% 
nd
100% 



Spec 2
 0%
nd
 0%
 0%
nd
 0%



Cutoff 3
0
nd
0
0
nd
0



Sens 3
100% 
nd
100% 
100% 
nd
100% 



Spec 3
 0%
nd
 0%
 0%
nd
 0%



Cutoff 4
9.52
nd
12.9
9.52
nd
12.9



Sens 4
33%
nd
 0%
33%
nd
 0%



Spec 4
74%
nd
75%
74%
nd
75%



Cutoff 5
22.1
nd
22.1
22.1
nd
22.1



Sens 5
33%
nd
 0%
33%
nd
 0%



Spec 5
81%
nd
82%
81%
nd
82%



Cutoff 6
33.9
nd
33.9
33.9
nd
33.9



Sens 6
33%
nd
 0%
33%
nd
 0%



Spec 6
91%
nd
91%
91%
nd
91%



OR Quart 2
0
nd
>1.2
0
nd
>1.2



p Value
na
nd
<0.90
na
nd
<0.90



95% CI of
na
nd
>0.066
na
nd
>0.066



OR Quart 2
na
nd
na
na
nd
na



OR Quart 3
1.0
nd
>0
1.0
nd
>0



p Value
1.0
nd
<na
1.0
nd
<na



95% CI of
0.056
nd
>na
0.056
nd
>na



OR Quart 3
18
nd
na
18
nd
na



OR Quart 4
1.0
nd
>1.2
1.0
nd
>1.2



p Value
1.0
nd
<0.90
1.0
nd
<0.90



95% CI of
0.056
nd
>0.066
0.056
nd
>0.066



OR Quart 4
18
nd
na
18
nd
na











Resistin

















0 hr prior to

24 hr prior to

48 hr prior to




AKI stage

AKI stage

AKI stage
















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
12400
41300
12400
37900
12400
41300



Average
17600
62700
17600
54500
17600
41600



Stdev
17400
45100
17400
41200
17400
8660



p (t-test)

4.8E−9

3.6E−7

5.3E−4



Min
1550
20000
1550
20000
1550
27500



Max
118000
150000
118000
150000
118000
53500



n (Samp)
88
11
88
11
88
7



n (Patient)
88
11
88
11
88
7



sCr only



Median
14400
41300
14400
41300
14400
41300



Average
21300
43900
21300
43900
21300
43900



Stdev
20200
7400
20200
7400
20200
7400



p (t-test)

0.014

0.014

0.014



Min
1550
36900
1550
36900
1550
36900



Max
135000
53500
135000
53500
135000
53500



n (Samp)
175
5
175
5
175
5



n (Patient)
175
5
175
5
175
5



UO only



Median
14000
49800
14000
32300
14000
44200



Average
21100
74400
21100
61500
21100
40500



Stdev
19100
54100
19100
51400
19100
11600



p (t-test)

5.5E−8

1.5E−5

0.084



Min
1620
20000
1620
20000
1620
27500



Max
118000
150000
118000
150000
118000
49800



n (Samp)
89
7
89
7
89
3



n (Patient)
89
7
89
7
89
3















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.91
0.90
0.87
0.90
0.90
0.84
0.91
0.90
0.85



SE
0.060
0.092
0.089
0.064
0.092
0.096
0.074
0.092
0.14



p
5.8E−12
1.1E−5
3.6E−5
3.7E−10
1.1E−5
4.6E−4
2.3E−8
1.1E−5
0.015



nCohort 1
88
175
89
88
175
89
88
175
89



nCohort 2
11
5
7
11
5
7
7
5
3



Cutoff 1
36600
37700
31200
32000
37700
31200
37700
37700
27100



Sens 1
73%
80%
71%
73%
80%
71%
71%
80%
100% 



Spec 1
89%
87%
79%
85%
87%
79%
90%
87%
72%



Cutoff 2
31100
37700
27100
31100
37700
27100
36600
37700
27100



Sens 2
82%
80%
86%
82%
80%
86%
86%
80%
100% 



Spec 2
85%
87%
72%
85%
87%
72%
89%
87%
72%



Cutoff 3
27100
36600
19500
27100
36600
19500
27100
36600
27100



Sens 3
91%
100% 
100% 
91%
100% 
100% 
100% 
100% 
100% 



Spec 3
81%
86%
63%
81%
86%
63%
81%
86%
72%



Cutoff 4
19200
26500
26600
19200
26500
26600
19200
26500
26600



Sens 4
100% 
100% 
86%
100% 
100% 
86%
100% 
100% 
100% 



Spec 4
70%
70%
71%
70%
70%
71%
70%
70%
71%



Cutoff 5
27100
32700
33400
27100
32700
33400
27100
32700
33400



Sens 5
91%
100% 
57%
91%
100% 
43%
100% 
100% 
67%



Spec 5
81%
80%
81%
81%
80%
81%
81%
80%
81%



Cutoff 6
38400
43900
45600
38400
43900
45600
38400
43900
45600



Sens 6
55%
40%
57%
45%
40%
43%
57%
40%
33%



Spec 6
91%
90%
91%
91%
90%
91%
91%
90%
91%



OR Quart 2
>0
>0
>0
>0
>0
>0
>0
>0
>0



p Value
<na
<na
<na
<na
<na
<na
<na
<na
<na



95% CI of
>na
>na
>na
>na
>na
>na
>na
>na
>na



OR Quart 2
na
na
na
na
na
na
na
na
na



OR Quart 3
>2.1
>0
>2.2
>2.1
>0
>2.2
>0
>0
>1.0



p Value
<0.56
<na
<0.54
<0.56
<na
<0.54
<na
<na
<0.98



95% CI of
>0.18
>na
>0.18
>0.18
>na
>0.18
>na
>na
>0.062



OR Quart 3
na
na
na
na
na
na
na
na
na



OR Quart 4
>14
>5.6
>6.3
>14
>5.6
>6.3
>9.5
>5.6
>2.2



p Value
<0.018
<0.12
<0.11
<0.018
<0.12
<0.11
<0.044
<0.12
<0.53



95% CI of
>1.6
>0.63
>0.68
>1.6
>0.63
>0.68
>1.1
>0.63
>0.18



OR Quart 4
na
na
na
na
na
na
na
na
na











Parathyroid hormone

















0 hr prior to

24 hr prior to

48 hr prior to




AKI stage

AKI stage

AKI stage
















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
31.8
90.1
31.8
90.1
31.8
63.8



Average
54.2
111
54.2
105
54.2
71.8



Stdev
75.9
86.3
75.9
72.3
75.9
40.9



p (t-test)

0.019

0.031

0.50



Min
6.72
15.7
6.72
15.7
6.72
12.7



Max
485
302
485
261
485
142



n (Samp)
59
13
59
13
59
9



n (Patient)
59
13
59
13
59
9



sCr only



Median
39.0
90.1
39.0
90.1
39.0
70.3



Average
61.0
85.1
61.0
85.1
61.0
81.6



Stdev
75.4
40.2
75.4
40.2
75.4
42.9



p (t-test)

0.40

0.40

0.51



Min
4.55
37.4
4.55
37.4
4.55
37.4



Max
506
142
506
142
506
142



n (Samp)
138
7
138
7
138
6



n (Patient)
138
7
138
7
138
6



UO only



Median
33.7
105
33.7
105
33.7
79.7



Average
64.7
136
64.7
125
64.7
77.6



Stdev
83.7
101
83.7
83.3
83.7
46.6



p (t-test)

0.030

0.058

0.73



Min
9.49
15.7
9.49
15.7
9.49
12.7



Max
485
302
485
261
485
142



n (Samp)
65
8
65
8
65
5



n (Patient)
65
8
65
8
65
5















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage



















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.80
0.77
0.76
0.80
0.77
0.76
0.73
0.75
0.66



SE
0.078
0.11
0.10
0.078
0.11
0.10
0.10
0.12
0.14



p
1.4E−4
0.010
0.011
1.4E−4
0.010
0.012
0.022
0.029
0.25



nCohort 1
59
138
65
59
138
65
59
138
65



nCohort 2
13
7
8
13
7
8
9
6
5



Cutoff 1
49.3
49.3
74.5
49.3
49.3
74.5
49.0
49.2
58.6



Sens 1
77%
71%
75%
77%
71%
75%
78%
83%
80%



Spec 1
75%
68%
80%
75%
68%
80%
75%
68%
74%



Cutoff 2
49.0
49.2
58.6
49.0
49.2
58.6
36.7
49.2
58.6



Sens 2
85%
86%
88%
85%
86%
88%
89%
83%
80%



Spec 2
75%
68%
74%
75%
68%
74%
64%
68%
74%



Cutoff 3
36.7
36.7
15.1
36.7
36.7
15.1
10.1
36.7
10.1



Sens 3
92%
100% 
100% 
92%
100% 
100% 
100% 
100% 
100% 



Spec 3
64%
49%
 8%
64%
49%
 8%
 5%
49%
 3%



Cutoff 4
43.2
54.5
54.5
43.2
54.5
54.5
43.2
54.5
54.5



Sens 4
85%
57%
88%
85%
57%
88%
78%
50%
80%



Spec 4
71%
70%
71%
71%
70%
71%
71%
70%
71%



Cutoff 5
58.6
74.5
74.5
58.6
74.5
74.5
58.6
74.5
74.5



Sens 5
69%
57%
75%
69%
57%
75%
56%
50%
60%



Spec 5
81%
80%
80%
81%
80%
80%
81%
80%
80%



Cutoff 6
121
123
132
121
123
132
121
123
132



Sens 6
23%
14%
38%
23%
14%
38%
11%
17%
20%



Spec 6
92%
91%
91%
92%
91%
91%
92%
91%
91%



OR Quart 2
0
>1.0
0
0
>1.0
0
0
>1.0
0



p Value
na
<0.98
na
na
<0.98
na
na
<0.98
na



95% CI of
na
>0.062
na
na
>0.062
na
na
>0.062
na



OR Quart 2
na
na
na
na
na
na
na
na
na



OR Quart 3
4.9
>2.1
1.0
4.9
>2.1
1.0
3.4
>2.1
1.0



p Value
0.18
<0.55
1.0
0.18
<0.55
1.0
0.31
<0.55
1.0



95% CI of
0.49
>0.18
0.058
0.49
>0.18
0.058
0.32
>0.18
0.057



OR Quart 3
49
na
17
49
na
17
37
na
17



OR Quart 4
14
>4.4
7.8
14
>4.4
7.8
6.7
>3.3
3.2



p Value
0.021
<0.20
0.071
0.021
<0.20
0.071
0.10
<0.31
0.34



95% CI of
1.5
>0.46
0.84
1.5
>0.46
0.84
0.69
>0.32
0.30



OR Quart 4
130
na
73
130
na
73
65
na
34











Serum albumin















0 hr prior to

24 hr prior to




AKI stage

AKI stage














Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
1.90E7
2.12E7
1.90E7
2.12E7



Average
1.92E7
1.73E7
1.92E7
1.73E7



Stdev
6580000
8940000
6580000
8940000



p (t-test)

0.65

0.65



Min
6690000
7090000
6690000
7090000



Max
3.44E7
2.36E7
3.44E7
2.36E7



n (Samp)
49
3
49
3



n (Patient)
49
3
49
3



UO only



Median
1.94E7
2.12E7
1.94E7
2.12E7



Average
1.96E7
1.73E7
1.96E7
1.73E7



Stdev
6690000
8940000
6690000
8940000



p (t-test)

0.58

0.58



Min
6690000
7090000
6690000
7090000



Max
3.44E7
2.36E7
3.44E7
2.36E7



n (Samp)
40
3
40
3



n (Patient)
40
3
40
3














0 hr prior to AKI stage
24 hr prior to AKI stage
















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only







AUC
0.49
nd
0.48
0.49
nd
0.48



SE
0.17
nd
0.18
0.17
nd
0.18



p
0.95
nd
0.92
0.95
nd
0.92



nCohort 1
49
nd
40
49
nd
40



nCohort 2
3
nd
3
3
nd
3



Cutoff 1
6690000
nd
6690000
6690000
nd
6690000



Sens 1
100% 
nd
100% 
100% 
nd
100% 



Spec 1
 2%
nd
 2%
 2%
nd
 2%



Cutoff 2
6690000
nd
6690000
6690000
nd
6690000



Sens 2
100% 
nd
100% 
100% 
nd
100% 



Spec 2
 2%
nd
 2%
 2%
nd
 2%



Cutoff 3
6690000
nd
6690000
6690000
nd
6690000



Sens 3
100% 
nd
100% 
100% 
nd
100% 



Spec 3
 2%
nd
 2%
 2%
nd
 2%



Cutoff 4
2.23E7
nd
2.23E7
2.23E7
nd
2.23E7



Sens 4
33%
nd
33%
33%
nd
33%



Spec 4
71%
nd
70%
71%
nd
70%



Cutoff 5
2.58E7
nd
2.36E7
2.58E7
nd
2.36E7



Sens 5
 0%
nd
33%
 0%
nd
33%



Spec 5
82%
nd
80%
82%
nd
80%



Cutoff 6
2.79E7
nd
2.66E7
2.79E7
nd
2.66E7



Sens 6
 0%
nd
 0%
 0%
nd
 0%



Spec 6
92%
nd
90%
92%
nd
90%



OR Quart 2
1.0
nd
1.0
1.0
nd
1.0



p Value
1.0
nd
1.0
1.0
nd
1.0



95% CI of
0.056
nd
0.055
0.056
nd
0.055



OR Quart 2
18
nd
18
18
nd
18



OR Quart 3
0
nd
0
0
nd
0



p Value
na
nd
na
na
nd
na



95% CI of
na
nd
na
na
nd
na



OR Quart 3
na
nd
na
na
nd
na



OR Quart 4
1.0
nd
1.1
1.0
nd
1.1



p Value
1.0
nd
0.94
1.0
nd
0.94



95% CI of
0.056
nd
0.060
0.056
nd
0.060



OR Quart 4
18
nd
20
18
nd
20

















TABLE 9





Comparison of marker levels in urine samples collected from Cohort


1 (patients that did not progress beyond RIFLE stage 0, R, or I) and in urine samples


collected from Cohort 2 (subjects who progress to RIFLE stage F) at 0, 24 hours, and 48


hours prior to the subject reaching RIFLE stage I.







Serum amyloid A protein

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
1.47
1.25
1.47
0.949
1.47
1.23



Average
62.1
4.45
62.1
302
62.1
1.70



Stdev
351
5.29
351
891
351
1.70



p (t-test)

0.62

0.051

0.67



Min
0.000310
0.649
0.000310
0.452
0.000310
0.385



Max
2680
15.2
2680
2680
2680
5.07



n (Samp)
573
9
573
9
573
6



n (Patient)
192
9
192
9
192
6



sCr only



Median
1.49
1.01
1.49
1.05
1.49
1.63



Average
64.8
1.01
64.8
1.24
64.8
2.29



Stdev
362
0.333
362
0.568
362
1.90



p (t-test)

0.80

0.70

0.73



Min
0.000310
0.779
0.000310
0.801
0.000310
0.829



Max
2680
1.25
2680
2.23
2680
5.07



n (Samp)
592
2
592
5
592
4



n (Patient)
199
2
199
5
199
4



UO only



Median
1.44
5.88
1.44
1.03
nd
nd



Average
58.6
6.20
58.6
388
nd
nd



Stdev
341
5.88
341
1010
nd
nd



p (t-test)

0.71

0.015
nd
nd



Min
0.000310
0.000551
0.000310
0.911
nd
nd



Max
2680
15.2
2680
2680
nd
nd



n (Samp)
609
6
609
7
nd
nd



n (Patient)
198
6
198
7
nd
nd















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.52
0.34
0.58
0.46
0.39
0.54
0.41
0.52
nd


SE
0.098
0.21
0.12
0.099
0.13
0.11
0.12
0.15
nd


p
0.84
0.45
0.50
0.71
0.43
0.69
0.46
0.92
nd


nCohort 1
573
592
609
573
592
609
573
592
nd


nCohort 2
9
2
6
9
5
7
6
4
nd


Cutoff 1
1.02
0.772
1.02
0.885
0.945
0.983
0.828
1.45
nd


Sens 1
78%
100% 
83%
78%
80%
71%
83%
75%
nd


Spec 1
35%
25%
36%
30%
31%
34%
27%
49%
nd


Cutoff 2
0.772
0.772
1.02
0.801
0.945
0.945
0.828
0.828
nd


Sens 2
89%
100% 
83%
89%
80%
86%
83%
100% 
nd


Spec 2
25%
25%
36%
26%
31%
33%
27%
27%
nd


Cutoff 3
0.642
0.772
0.000529
0.435
0.801
0.910
0.377
0.828
nd


Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 3
21%
25%
 2%
11%
26%
31%
 9%
27%
nd


Cutoff 4
3.56
3.58
3.34
3.56
3.58
3.34
3.56
3.58
nd


Sens 4
33%
 0%
50%
22%
 0%
29%
17%
25%
nd


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
nd


Cutoff 5
10.8
10.7
9.74
10.8
10.7
9.74
10.8
10.7
nd


Sens 5
11%
 0%
17%
22%
 0%
29%
 0%
 0%
nd


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
nd


Cutoff 6
26.8
26.8
25.7
26.8
26.8
25.7
26.8
26.8
nd


Sens 6
 0%
 0%
 0%
22%
 0%
29%
 0%
 0%
nd


Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
nd


OR Quart 2
4.1
>0
0.99
0.50
>1.0
>4.1
>1.0
>2.0
nd


p Value
0.21
<na
1.00
0.57
<0.99
<0.21
<1.00
<0.57
nd


95% CI of
0.45
>na
0.062
0.045
>0.063
>0.45
>0.062
>0.18
nd


OR Quart 2
37
na
16
5.6
na
na
na
na
nd


OR Quart 3
1.0
>1.0
0.99
2.6
>4.1
>1.0
>4.1
>2.0
nd


p Value
1.0
<1.00
1.00
0.27
<0.21
<1.00
<0.21
<0.57
nd


95% CI of
0.062
>0.062
0.062
0.49
>0.46
>0.062
>0.45
>0.18
nd


OR Quart 3
16
na
16
13
na
na
na
na
nd


OR Quart 4
3.0
>1.0
3.0
0.50
>0
>2.0
>1.0
>0
nd


p Value
0.34
<0.99
0.34
0.57
<na
<0.57
<0.99
<na
nd


95% CI of
0.31
>0.063
0.31
0.045
>na
>0.18
>0.063
>na
nd


OR Quart 4
29
na
29
5.6
na
na
na
na
nd










Tissue-type plasminogen activator

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
0.135
0.00567
0.135
1.13
0.135
0.00314



Average
45.3
0.0194
45.3
21.8
45.3
2.31



Stdev
282
0.0435
282
46.6
282
5.62



p (t-test)

0.63

0.80

0.71



Min
0.00252
0.00252
0.00252
0.00567
0.00252
0.00252



Max
4790
0.135
4790
143
4790
13.8



n (Samp)
573
9
573
9
573
6



n (Patient)
192
9
192
9
192
6



sCr only



Median
0.135
0.00567
0.135
4.04
0.135
6.89



Average
44.6
0.00567
44.6
4.67
44.6
9.70



Stdev
278
0
278
5.16
278
12.1



p (t-test)

0.82

0.75

0.80



Min
0.00252
0.00567
0.00252
0.00567
0.00252
0.00297



Max
4790
0.00567
4790
12.2
4790
25.0



n (Samp)
592
2
592
5
592
4



n (Patient)
199
2
199
5
199
4



UO only



Median
0.135
0.00564
0.135
9.62
nd
nd



Average
43.5
7.41
43.5
28.7
nd
nd



Stdev
274
18.1
274
51.6
nd
nd



p (t-test)

0.75

0.89
nd
nd



Min
0.00252
0.00297
0.00252
0.00252
nd
nd



Max
4790
44.4
4790
143
nd
nd



n (Samp)
609
6
609
7
nd
nd



n (Patient)
198
6
198
7
nd
nd















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.25
0.31
0.31
0.57
0.52
0.55
0.23
0.42
nd


SE
0.095
0.21
0.12
0.10
0.13
0.11
0.11
0.15
nd


p
0.0099
0.37
0.12
0.51
0.85
0.67
0.020
0.57
nd


nCohort 1
573
592
609
573
592
609
573
592
nd


nCohort 2
9
2
6
9
5
7
6
4
nd


Cutoff 1
0.00503
0.00564
0.00314
0.00564
0.00564
0.00564
0.00252
0.00297
nd


Sens 1
78%
100% 
83%
100% 
100% 
86%
83%
75%
nd


Spec 1
22%
29%
12%
29%
29%
28%
 3%
 8%
nd


Cutoff 2
0.00252
0.00564
0.00314
0.00564
0.00564
0.00564
0.00252
0.00252
nd


Sens 2
89%
100% 
83%
100% 
100% 
86%
83%
100% 
nd


Spec 2
 3%
29%
12%
29%
29%
28%
 3%
 4%
nd


Cutoff 3
0
0.00564
0.00252
0.00564
0.00564
0
0
0.00252
nd


Sens 3
100% 
100% 
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 3
 0%
29%
 3%
29%
29%
 0%
 0%
 4%
nd


Cutoff 4
10.3
10.1
10.1
10.3
10.1
10.1
10.3
10.1
nd


Sens 4
 0%
 0%
17%
33%
20%
43%
17%
50%
nd


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
nd


Cutoff 5
28.0
27.9
27.3
28.0
27.9
27.3
28.0
27.9
nd


Sens 5
 0%
 0%
17%
11%
 0%
14%
 0%
 0%
nd


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
nd


Cutoff 6
67.8
67.8
68.4
67.8
67.8
68.4
67.8
67.8
nd


Sens 6
 0%
 0%
 0%
11%
 0%
14%
 0%
 0%
nd


Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
nd


OR Quart 2
>0
>0
0
>3.0
>2.0
2.0
>1.0
1.0
nd


p Value
<na
<na
na
<0.34
<0.57
0.57
<1.00
1.0
nd


95% CI of
>na
>na
na
>0.31
>0.18
0.18
>0.062
0.062
nd


OR Quart 2
na
na
na
na
na
22
na
16
nd


OR Quart 3
>5.2
>2.0
1.0
>3.1
>3.1
1.0
>1.0
0
nd


p Value
<0.14
<0.57
1.0
<0.33
<0.33
1.0
<1.00
na
nd


95% CI of
>0.60
>0.18
0.062
>0.31
>0.31
0.062
>0.062
na
nd


OR Quart 3
na
na
16
na
na
16
na
na
nd


OR Quart 4
>4.1
>0
4.1
>3.0
>0
3.0
>4.1
2.0
nd


p Value
<0.21
<na
0.21
<0.34
<na
0.34
<0.21
0.57
nd


95% CI of
>0.46
>na
0.45
>0.31
>na
0.31
>0.46
0.18
nd


OR Quart 4
na
na
37
na
na
30
na
22
nd










Protein S100-B













24 hr prior to AKI stage













Cohort 1
Cohort 2







sCr or UO



Median
0.0871
15.7



Average
14.6
199



Stdev
56.5
462



p (t-test)

9.5E−5



Min
0.0517
3.13



Max
576
1240



n (Samp)
115
7



n (Patient)
90
7



sCr only



Median
0.0871
23.8



Average
25.2
20.8



Stdev
125
16.4



p (t-test)

0.95



Min
0.0517
3.13



Max
1240
35.5



n (Samp)
120
3



n (Patient)
94
3



UO only



Median
0.0871
15.7



Average
16.1
270



Stdev
60.9
546



p (t-test)

2.0E−5



Min
0.0517
3.74



Max
576
1240



n (Samp)
98
5



n (Patient)
77
5













24 hr prior to AKI stage













sCr or UO
sCr only
UO only







AUC
0.82
0.80
0.82



SE
0.100
0.16
0.12



p
0.0015
0.057
0.0058



nCohort 1
115
120
98



nCohort 2
7
3
5



Cutoff 1
3.74
1.55
3.74



Sens 1
71%
100% 
80%



Spec 1
66%
63%
65%



Cutoff 2
3.13
1.55
3.74



Sens 2
86%
100% 
80%



Spec 2
66%
63%
65%



Cutoff 3
1.55
1.55
3.13



Sens 3
100% 
100% 
100% 



Spec 3
66%
63%
65%



Cutoff 4
6.21
7.37
6.21



Sens 4
57%
67%
60%



Spec 4
71%
71%
70%



Cutoff 5
13.6
14.0
14.0



Sens 5
57%
67%
60%



Spec 5
80%
80%
81%



Cutoff 6
26.8
34.9
34.9



Sens 6
43%
33%
40%



Spec 6
90%
90%
91%



OR Quart 2
>0
>0
>0



p Value
<na
<na
<na



95% CI of
>na
>na
>na



OR Quart 2
na
na
na



OR Quart 3
>3.3
>1.0
>2.1



p Value
<0.31
<1.0
<0.56



95% CI of
>0.33
>0.060
>0.18



OR Quart 3
na
na
na



OR Quart 4
>4.4
>2.1
>3.3



p Value
<0.19
<0.56
<0.32



95% CI of
>0.47
>0.18
>0.32



OR Quart 4
na
na
na











Resistin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
44900
47500
44900
48400
44900
36200



Average
50200
53800
50200
53200
50200
39500



Stdev
25600
18600
25600
23500
25600
22800



p (t-test)

0.49

0.55

0.15



Min
863
27200
863
15800
863
1060



Max
150000
100000
150000
101000
150000
85200



n (Samp)
1554
24
1554
26
1554
12



n (Patient)
464
24
464
26
464
12



sCr only



Median
44900
48400
44900
47200
44900
36300



Average
50100
52200
50100
49100
50100
43600



Stdev
25300
11900
25300
20700
25300
19500



p (t-test)

0.78

0.88

0.40



Min
863
38600
863
15800
863
24700



Max
150000
72400
150000
100000
150000
85200



n (Samp)
1614
11
1614
15
1614
11



n (Patient)
480
11
480
15
480
11



UO only



Median
45300
42900
45300
45800
45300
35600



Average
50400
46300
50400
49400
50400
35600



Stdev
25400
13700
25400
22900
25400
18700



p (t-test)

0.55

0.87

0.41



Min
863
27200
863
20700
863
22300



Max
150000
78300
150000
100000
150000
48800



n (Samp)
1638
13
1638
17
1638
2



n (Patient)
465
13
465
17
465
2















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.58
0.59
0.48
0.55
0.51
0.49
0.37
0.42
0.33


SE
0.061
0.091
0.081
0.059
0.075
0.071
0.087
0.091
0.21


p
0.20
0.33
0.82
0.41
0.89
0.87
0.15
0.35
0.42


nCohort 1
1554
1614
1638
1554
1614
1638
1554
1614
1638


nCohort 2
24
11
13
26
15
17
12
11
2


Cutoff 1
42900
43100
37600
37100
38400
34300
26200
31300
22200


Sens 1
71%
73%
77%
73%
73%
71%
75%
73%
100% 


Spec 1
46%
47%
34%
34%
37%
27%
15%
22%
10%


Cutoff 2
39900
41100
36300
34400
36100
30000
24700
27800
22200


Sens 2
83%
82%
85%
81%
80%
82%
83%
82%
100% 


Spec 2
40%
43%
32%
29%
32%
20%
13%
17%
10%


Cutoff 3
38600
40200
34900
28200
28200
26400
22200
26200
22200


Sens 3
92%
91%
92%
92%
93%
94%
92%
91%
100% 


Spec 3
38%
41%
29%
18%
17%
14%
10%
15%
10%


Cutoff 4
58400
58200
58900
58400
58200
58900
58400
58200
58900


Sens 4
38%
36%
15%
35%
27%
35%
17%
18%
 0%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
70100
69400
70400
70100
69400
70400
70100
69400
70400


Sens 5
17%
 9%
 8%
15%
13%
12%
17%
18%
 0%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
100000
99000
99000
100000
99000
99000
100000
99000
99000


Sens 6
 0%
 0%
 0%
 4%
 7%
 6%
 0%
 0%
 0%


Spec 6
99%
90%
90%
99%
90%
90%
99%
90%
90%


OR Quart 2
10
>4.0
4.0
1.3
1.0
3.5
1.0
1.0
>1.0


p Value
0.027
<0.21
0.21
0.74
1.0
0.12
1.00
1.00
<1.00


95% CI of
1.3
>0.45
0.45
0.33
0.20
0.73
0.14
0.14
>0.062


OR Quart 2
80
na
36
4.7
5.0
17
7.2
7.2
na


OR Quart 3
8.1
>5.1
7.1
3.3
2.0
1.5
1.5
1.5
>0


p Value
0.048
<0.14
0.067
0.037
0.32
0.66
0.66
0.65
<na


95% CI of
1.0
>0.59
0.87
1.1
0.50
0.25
0.25
0.25
>na


OR Quart 3
65
na
58
10
8.1
9.0
9.0
9.1
na


OR Quart 4
5.0
>2.0
1.0
1.0
1.00
2.5
2.5
2.0
>1.0


p Value
0.14
<0.57
1.00
1.0
1.00
0.27
0.27
0.42
<1.00


95% CI of
0.59
>0.18
0.062
0.25
0.20
0.49
0.49
0.37
>0.062


OR Quart 4
43
na
16
4.0
5.0
13
13
11
na










Parathyroid hormone

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
16.9
10.2
16.9
9.50
16.9
12.5



Average
22.9
20.5
22.9
15.6
22.9
20.1



Stdev
26.3
24.1
26.3
14.4
26.3
25.0



p (t-test)

0.59

0.16

0.66



Min
0.000320
0.00185
0.000320
0.427
0.000320
0.0488



Max
433
96.9
433
52.8
433
90.6



n (Samp)
1867
37
1867
26
1867
18



n (Patient)
576
37
576
26
576
18



sCr only



Median
16.8
7.98
16.8
7.79
16.8
11.1



Average
23.0
18.9
23.0
15.4
23.0
13.1



Stdev
26.9
23.0
26.9
15.3
26.9
11.2



p (t-test)

0.55

0.32

0.17



Min
0.000320
0.00185
0.000320
4.68
0.000320
0.683



Max
433
75.7
433
52.8
433
33.5



n (Samp)
1957
15
1957
12
1957
14



n (Patient)
600
15
600
12
600
14



UO only



Median
16.6
8.53
16.6
15.7
16.6
6.12



Average
22.7
19.0
22.7
17.4
22.7
20.1



Stdev
26.1
21.1
26.1
13.5
26.1
32.5



p (t-test)

0.50

0.38

0.79



Min
0.000320
0.147
0.000320
0.427
0.000320
0.0488



Max
433
76.6
433
51.6
433
90.6



n (Samp)
1926
23
1926
19
1926
7



n (Patient)
566
23
566
19
566
7















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.43
0.40
0.42
0.41
0.40
0.46
0.42
0.38
0.35


SE
0.049
0.078
0.063
0.059
0.087
0.068
0.071
0.080
0.11


p
0.17
0.22
0.23
0.12
0.25
0.58
0.27
0.13
0.20


nCohort 1
1867
1957
1926
1867
1957
1926
1867
1957
1926


nCohort 2
37
15
23
26
12
19
18
14
7


Cutoff 1
6.66
6.66
5.43
6.28
6.06
8.07
5.75
5.27
0.532


Sens 1
70%
73%
74%
73%
75%
74%
72%
71%
71%


Spec 1
23%
24%
19%
22%
21%
28%
20%
19%
 3%


Cutoff 2
2.59
5.41
2.38
5.29
5.50
4.64
0.664
1.24
0.531


Sens 2
81%
80%
83%
81%
83%
84%
83%
86%
86%


Spec 2
11%
19%
 9%
19%
20%
16%
 4%
 7%
 3%


Cutoff 3
1.04
1.04
1.76
2.32
5.29
1.24
0.531
0.707
0.0448


Sens 3
92%
93%
91%
92%
92%
95%
94%
93%
100% 


Spec 3
 6%
 6%
 7%
10%
19%
 6%
 3%
 4%
 1%


Cutoff 4
26.0
26.0
25.8
26.0
26.0
25.8
26.0
26.0
25.8


Sens 4
27%
27%
26%
19%
25%
21%
22%
14%
14%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
33.7
33.7
33.3
33.7
33.7
33.3
33.7
33.7
33.3


Sens 5
19%
20%
22%
15%
17%
16%
11%
 0%
14%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
49.2
49.4
48.9
49.2
49.4
48.9
49.2
49.4
48.9


Sens 6
11%
13%
 9%
 8%
 8%
 5%
11%
 0%
14%


Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%


OR Quart 2
0.75
0
0.80
0.80
0
1.3
1.0
4.0
2.0


p Value
0.59
na
0.74
0.74
na
0.74
1.00
0.21
0.57


95% CI of
0.26
na
0.21
0.21
na
0.34
0.25
0.45
0.18


OR Quart 2
2.2
na
3.0
3.0
na
4.7
4.0
36
22


OR Quart 3
1.1
1.5
0.60
1.6
1.7
1.3
0.50
3.0
0


p Value
0.81
0.53
0.48
0.40
0.48
0.74
0.42
0.34
na


95% CI of
0.43
0.42
0.14
0.52
0.40
0.34
0.091
0.31
na


OR Quart 3
2.9
5.4
2.5
5.0
7.1
4.7
2.7
29
na


OR Quart 4
1.8
1.3
2.2
1.8
1.3
1.3
2.0
6.1
4.0


p Value
0.20
0.74
0.14
0.29
0.70
0.74
0.25
0.095
0.21


95% CI of
0.74
0.33
0.77
0.61
0.30
0.34
0.60
0.73
0.45


OR Quart 4
4.3
4.7
6.5
5.5
6.0
4.7
6.8
51
36










Serum albumin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
28000
69600
28000
62300
28000
19300



Average
70400
129000
70400
192000
70400
48400



Stdev
158000
112000
158000
341000
158000
90200



p (t-test)

0.072

1.6E−4

0.63



Min
0.846
6870
0.846
3140
0.846
1.10



Max
1830000
371000
1830000
1280000
1830000
324000



n (Samp)
1537
24
1537
26
1537
12



n (Patient)
462
24
462
26
462
12



sCr only



Median
29000
30000
29000
53800
29000
40000



Average
77700
69100
77700
118000
77700
76800



Stdev
173000
84500
173000
250000
173000
96600



p (t-test)

0.87

0.38

0.99



Min
0.846
5430
0.846
3140
0.846
1.10



Max
1830000
252000
1830000
1010000
1830000
324000



n (Samp)
1597
11
1597
15
1597
11



n (Patient)
478
11
478
15
478
11



UO only



Median
28300
163000
28300
96500
28300
6080



Average
70600
158000
70600
213000
70600
6080



Stdev
156000
122000
156000
358000
156000
3500



p (t-test)

0.044

2.5E−4

0.56



Min
0.846
14800
0.846
10200
0.846
3600



Max
1830000
371000
1830000
1280000
1830000
8560



n (Samp)
1621
13
1621
17
1621
2



n (Patient)
463
13
463
17
463
2















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.72
0.53
0.77
0.68
0.59
0.73
0.40
0.56
0.16


SE
0.059
0.089
0.077
0.059
0.078
0.070
0.087
0.090
0.17


p
1.7E−4
0.76
3.4E−4
0.0028
0.27
0.0011
0.25
0.47
0.049


nCohort
1537
1597
1621
1537
1597
1621
1537
1597
1621


1


nCohort
24
11
13
26
15
17
12
11
2


2


Cutoff 1
53500
16400
36400
19900
15200
56100
3700
25900
3550


Sens 1
71%
73%
77%
73%
73%
71%
75%
73%
100% 


Spec 1
69%
36%
57%
42%
34%
71%
11%
47%
10%


Cutoff 2
27200
6800
30000
16600
14200
29100
3550
12500
3550


Sens 2
83%
82%
85%
81%
80%
82%
83%
82%
100% 


Spec 2
49%
17%
52%
37%
32%
51%
11%
29%
10%


Cutoff 3
14800
6190
26900
13100
12800
10700
38.9
12300
3550


Sens 3
92%
91%
92%
92%
93%
94%
92%
91%
100% 


Spec 3
34%
16%
49%
31%
29%
26%
 2%
28%
10%


Cutoff 4
54300
57800
54500
54300
57800
54500
54300
57800
54500


Sens 4
62%
27%
69%
62%
40%
71%
25%
36%
 0%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
82100
89000
83700
82100
89000
83700
82100
89000
83700


Sens 5
46%
27%
62%
46%
33%
53%
 8%
27%
 0%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
147000
163000
147000
147000
163000
147000
147000
163000
147000


Sens 6
42%
18%
54%
23%
 7%
29%
 8%
18%
 0%


Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%


OR
1.5
0.66
>2.0
7.1
5.1
2.0
1.0
4.0
>0


Quart 2


p Value
0.66
0.66
<0.57
0.068
0.14
0.57
1.00
0.21
<na


95% CI
0.25
0.11
>0.18
0.87
0.59
0.18
0.14
0.45
>na


of


OR
9.1
4.0
na
58
43
22
7.2
36
na


Quart 2


OR
3.5
1.0
>3.0
6.1
4.0
5.0
1.5
3.0
>0


Quart 3


p Value
0.12
1.0
<0.34
0.096
0.21
0.14
0.65
0.34
<na


95% CI
0.73
0.20
>0.31
0.73
0.45
0.59
0.25
0.31
>na


of


OR
17
5.0
na
51
36
43
9.1
29
na


QuaA3


OR
6.1
1.0
>8.1
12
5.1
9.2
2.5
3.0
>2.0


Quart 4


p Value
0.018
1.0
<0.049
0.016
0.14
0.036
0.27
0.34
<0.57


95% CI
1.4
0.20
>1.0
1.6
0.59
1.2
0.49
0.31
>0.18


of


OR
28
5.0
na
95
43
73
13
29
na


Quart 4










Cortisol

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
156
150
156
170
156
76.7



Average
289
389
289
315
289
239



Stdev
332
416
332
357
332
404



p (t-test)

0.053

0.64

0.50



Min
0.000854
28.0
0.000854
21.6
0.000854
16.9



Max
1500
1460
1500
1500
1500
1500



n (Samp)
2326
42
2326
37
2326
21



n (Patient)
749
42
749
37
749
21



sCr only



Median
158
189
158
53.8
158
76.7



Average
294
508
294
213
294
167



Stdev
335
542
335
316
335
253



p (t-test)

0.011

0.34

0.14



Min
0.000854
31.7
0.000854
21.6
0.000854
27.8



Max
1500
1500
1500
1000
1500
1000



n (Samp)
2430
16
2430
16
2430
15



n (Patient)
773
16
773
16
773
15



UO only



Median
158
144
158
188
158
100



Average
293
325
293
313
293
344



Stdev
337
351
337
351
337
532



p (t-test)

0.63

0.76

0.65



Min
1.42
36.0
1.42
22.3
1.42
16.9



Max
1500
1090
1500
1500
1500
1500



n (Samp)
2291
27
2291
30
2291
9



n (Patient)
677
27
677
30
677
9















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.54
0.54
0.52
0.51
0.34
0.53
0.36
0.34
0.42


SE
0.046
0.074
0.056
0.048
0.075
0.054
0.066
0.077
0.100


p
0.38
0.61
0.76
0.77
0.034
0.55
0.031
0.033
0.42


nCohort 1
2326
2430
2291
2326
2430
2291
2326
2430
2291


nCohort 2
42
16
27
37
16
30
21
15
9


Cutoff 1
81.5
44.9
105
89.9
36.0
104
45.5
45.5
46.5


Sens 1
71%
75%
70%
70%
75%
70%
71%
73%
78%


Spec 1
28%
13%
36%
31%
11%
36%
14%
14%
14%


Cutoff 2
67.6
41.6
73.2
53.0
33.2
76.0
33.0
33.2
17.6


Sens 2
81%
81%
81%
81%
81%
80%
81%
80%
89%


Spec 2
23%
12%
25%
17%
10%
26%
10%
10%
 3%


Cutoff 3
47.3
35.9
50.9
33.2
27.8
52.9
21.7
30.3
16.8


Sens 3
90%
94%
93%
92%
94%
90%
90%
93%
100% 


Spec 3
15%
10%
16%
10%
 7%
16%
 5%
 8%
 3%


Cutoff 4
282
291
286
282
291
286
282
291
286


Sens 4
36%
44%
30%
35%
19%
33%
14%
13%
22%


Spec 4
70%
70%
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
458
473
462
458
473
462
458
473
462


Sens 5
33%
44%
30%
22%
19%
20%
14%
 7%
22%


Spec 5
80%
80%
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
816
820
824
816
820
824
816
820
824


Sens 6
24%
38%
15%
11%
 6%
10%
14%
 7%
22%


Spec 6
90%
90%
90%
90%
90%
90%
90%
90%
90%


OR Quart 2
1.0
0
2.4
1.00
0.33
1.6
1.0
1.0
0.50


p Value
1.0
na
0.098
1.00
0.34
0.41
1.0
1.00
0.57


95% CI of
0.43
na
0.85
0.39
0.035
0.52
0.20
0.14
0.045


OR Quart 2
2.3
na
6.9
2.5
3.2
4.9
5.0
7.1
5.5


OR Quart 3
0.54
0.28
0.40
1.00
1.0
1.8
2.0
2.0
1.5


p Value
0.23
0.12
0.27
1.00
1.0
0.29
0.33
0.42
0.66


95% CI of
0.20
0.059
0.077
0.39
0.20
0.60
0.50
0.37
0.25


OR QuaA3
1.5
1.4
2.1
2.5
5.0
5.4
8.1
11
9.0


OR Quart 4
1.3
1.00
1.6
1.1
3.0
1.6
3.0
3.5
1.5


p Value
0.55
1.00
0.41
0.82
0.097
0.41
0.097
0.12
0.66


95% CI of
0.58
0.35
0.52
0.45
0.82
0.52
0.82
0.73
0.25


OR Quart 4
2.8
2.9
4.9
2.8
11
4.9
11
17
9.0
















TABLE 10





Comparison of marker levels in EDTA samples collected from


Cohort 1 (patients that did not progress beyond RIFLE stage 0, R, or I) and in EDTA


samples collected from Cohort 2 (subjects who progress to RIFLE stage F) at 0, 24 hours,


and 48 hours prior to the subject reaching RIFLE stage I.







Serum amyloid A protein

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
67100
1340000
67100
700000
67100
460000



Average
672000
1500000
672000
689000
672000
570000



Stdev
822000
1130000
822000
751000
822000
656000



p (t-test)

0.026

0.97

0.81



Min
16.4
24000
16.4
17200
16.4
21800



Max
2630000
2630000
2630000
1340000
2630000
1340000



n (Samp)
361
5
361
4
361
4



n (Patient)
119
5
119
4
119
4



sCr only



Median
nd
nd
69400
682000
69400
27200



Average
nd
nd
699000
682000
699000
463000



Stdev
nd
nd
850000
929000
850000
759000



p (t-test)
nd
nd

0.98

0.63



Min
nd
nd
16.4
25500
16.4
22000



Max
nd
nd
2630000
1340000
2630000
1340000



n (Samp)
nd
nd
372
2
372
3



n (Patient)
nd
nd
122
2
122
3



UO only



Median
71200
2630000
71200
61200
nd
nd



Average
673000
2300000
673000
484000
nd
nd



Stdev
819000
643000
819000
741000
nd
nd



p (t-test)

8.7E−5

0.69
nd
nd



Min
16.4
1340000
16.4
52000
nd
nd



Max
2630000
2630000
2630000
1340000
nd
nd



n (Samp)
377
4
377
3
nd
nd



n (Patient)
121
4
121
3
nd
nd















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.72
nd
0.92
0.57
0.52
0.60
0.49
0.43
nd


SE
0.13
nd
0.094
0.15
0.21
0.17
0.15
0.17
nd


p
0.097
nd
8.8E−6
0.63
0.92
0.58
0.92
0.68
nd


nCohort 1
361
nd
377
361
372
377
361
372
nd


nCohort 2
5
nd
4
4
2
3
4
3
nd


Cutoff 1
523000
nd
1340000
60900
25300
51900
27200
21200
nd


Sens 1
80%
nd
75%
75%
100% 
100% 
75%
100% 
nd


Spec 1
54%
nd
90%
50%
23%
47%
28%
20%
nd


Cutoff 2
523000
nd
1180000
17100
25300
51900
21200
21200
nd


Sens 2
80%
nd
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 2
54%
nd
74%
15%
23%
47%
20%
20%
nd


Cutoff 3
23700
nd
1180000
17100
25300
51900
21200
21200
nd


Sens 3
100% 
nd
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 3
22%
nd
74%
15%
23%
47%
20%
20%
nd


Cutoff 4
893000
nd
893000
893000
893000
893000
893000
893000
nd


Sens 4
60%
nd
100% 
50%
50%
33%
25%
33%
nd


Spec 4
73%
nd
73%
73%
72%
73%
73%
72%
nd


Cutoff 5
1340000
nd
1340000
1340000
1340000
1340000
1340000
1340000
nd


Sens 5
40%
nd
75%
 0%
 0%
 0%
 0%
 0%
nd


Spec 5
90%
nd
90%
90%
89%
90%
90%
89%
nd


Cutoff 6
1340000
nd
1340000
1340000
2630000
1340000
1340000
2630000
nd


Sens 6
40%
nd
75%
 0%
 0%
 0%
 0%
 0%
nd


Spec 6
90%
nd
90%
90%
100% 
90%
90%
100% 
nd


OR Quart 2
0
nd
>0
1.0
0
>2.0
1.0
0
nd


p Value
na
nd
<na
1.0
na
<0.56
0.99
na
nd


95% CI of
na
nd
>na
0.062
na
>0.18
0.062
na
nd


OR Quart 2
na
nd
na
16
na
na
16
na
nd


OR Quart 3
2.0
nd
>0
0
0
>0
1.0
1.0
nd


p Value
0.57
nd
<na
na
na
<na
0.99
1.0
nd


95% CI of
0.18
nd
>na
na
na
>na
0.062
0.062
nd


OR Quart 3
23
nd
na
na
na
na
16
16
nd


OR Quart 4
2.0
nd
>4.1
2.0
0.99
>1.0
1.0
1.0
nd


p Value
0.57
nd
<0.21
0.57
0.99
<0.99
0.99
0.99
nd


95% CI of
0.18
nd
>0.45
0.18
0.061
>0.062
0.062
0.062
nd


OR Quart 4
22
nd
na
22
16
na
16
16
nd










Tissue-type plasminogen activator

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
8090
9750
8090
7010
8090
5120



Average
9380
10700
9380
8330
9380
7030



Stdev
7750
9540
7750
4180
7750
6800



p (t-test)

0.71

0.79

0.55



Min
0.840
1140
0.840
4910
0.840
1070



Max
70800
22900
70800
14400
70800
16800



n (Samp)
361
5
361
4
361
4



n (Patient)
119
5
119
4
119
4



sCr only



Median
nd
nd
8110
5240
8110
5000



Average
nd
nd
9420
5240
9420
3480



Stdev
nd
nd
7730
3010
7730
2830



p (t-test)
nd
nd

0.45

0.18



Min
nd
nd
0.840
3110
0.840
211



Max
nd
nd
70800
7370
70800
5230



n (Samp)
nd
nd
372
2
372
3



n (Patient)
nd
nd
122
2
122
3



UO only



Median
7710
13400
7710
4910
nd
nd



Average
9230
12700
9230
7020
nd
nd



Stdev
7680
9540
7680
6600
nd
nd



p (t-test)

0.37

0.62
nd
nd



Min
0.840
1140
0.840
1730
nd
nd



Max
70800
22900
70800
14400
nd
nd



n (Samp)
377
4
377
3
nd
nd



n (Patient)
121
4
121
3
nd
nd















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.52
nd
0.63
0.50
0.32
0.40
0.38
0.20
nd


SE
0.13
nd
0.15
0.15
0.21
0.17
0.15
0.16
nd


p
0.87
nd
0.40
1.00
0.38
0.58
0.43
0.057
nd


nCohort 1
361
nd
377
361
372
377
361
372
nd


nCohort 2
5
nd
4
4
2
3
4
3
nd


Cutoff 1
1910
nd
9170
6630
3110
1710
4960
72.1
nd


Sens 1
80%
nd
75%
75%
100% 
100% 
75%
100% 
nd


Spec 1
10%
nd
60%
42%
16%
 9%
27%
 3%
nd


Cutoff 2
1910
nd
1070
4860
3110
1710
1040
72.1
nd


Sens 2
80%
nd
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 2
10%
nd
 5%
27%
16%
 9%
 5%
 3%
nd


Cutoff 3
1040
nd
1070
4860
3110
1710
1040
72.1
nd


Sens 3
100% 
nd
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 3
 5%
nd
 5%
27%
16%
 9%
 5%
 3%
nd


Cutoff 4
11400
nd
11200
11400
11500
11200
11400
11500
nd


Sens 4
40%
nd
50%
25%
 0%
33%
25%
 0%
nd


Spec 4
70%
nd
70%
70%
70%
70%
70%
70%
nd


Cutoff 5
13000
nd
13000
13000
13300
13000
13000
13300
nd


Sens 5
40%
nd
50%
25%
 0%
33%
25%
 0%
nd


Spec 5
80%
nd
80%
80%
80%
80%
80%
80%
nd


Cutoff 6
17100
nd
17100
17100
17400
17100
17100
17400
nd


Sens 6
40%
nd
50%
 0%
 0%
 0%
 0%
 0%
nd


Spec 6
90%
nd
90%
90%
90%
90%
90%
90%
nd


OR Quart 2
0
nd
0
>3.1
>0
0
0
>0
nd


p Value
na
nd
na
<0.33
<na
na
na
<na
nd


95% CI of
na
nd
na
>0.32
>na
na
na
>na
nd


OR Quart 2
na
nd
na
na
na
na
na
na
nd


OR Quart 3
0.49
nd
1.0
>0
>1.0
1.0
2.0
>2.0
nd


p Value
0.57
nd
1.0
<na
<0.99
1.0
0.56
<0.56
nd


95% CI of
0.044
nd
0.062
>na
>0.062
0.062
0.18
>0.18
nd


OR Quart 3
5.6
nd
16
na
na
16
23
na
nd


OR Quart 4
0.99
nd
2.0
>1.0
>1.0
1.0
1.0
>1.0
nd


p Value
0.99
nd
0.57
<1.0
<0.99
1.0
0.99
<0.99
nd


95% CI of
0.14
nd
0.18
>0.062
>0.063
0.062
0.062
>0.063
nd


OR Quart 4
7.2
nd
22
na
na
16
16
na
nd










Protein S100-B













24 hr prior to AKI stage













Cohort 1
Cohort 2







sCr or UO



Median
3.32
2.93



Average
15.8
2.93



Stdev
42.6
4.03



p (t-test)

0.67



Min
0.0774
0.0774



Max
368
5.77



n (Samp)
129
2



n (Patient)
106
2



UO only



Median
3.32
2.93



Average
16.9
2.93



Stdev
45.3
4.03



p (t-test)

0.66



Min
0.0774
0.0774



Max
368
5.77



n (Samp)
113
2



n (Patient)
90
2













24 hr prior to AKI stage













sCr or UO
sCr only
UO only







AUC
0.34
nd
0.34



SE
0.21
nd
0.21



p
0.44
nd
0.45



nCohort 1
129
nd
113



nCohort 2
2
nd
2



Cutoff 1
0
nd
0



Sens 1
100% 
nd
100% 



Spec 1
 0%
nd
 0%



Cutoff 2
0
nd
0



Sens 2
100% 
nd
100% 



Spec 2
 0%
nd
 0%



Cutoff 3
0
nd
0



Sens 3
100% 
nd
100% 



Spec 3
 0%
nd
 0%



Cutoff 4
12.9
nd
12.9



Sens 4
 0%
nd
 0%



Spec 4
74%
nd
73%



Cutoff 5
18.4
nd
22.1



Sens 5
 0%
nd
 0%



Spec 5
81%
nd
81%



Cutoff 6
31.8
nd
31.8



Sens 6
 0%
nd
 0%



Spec 6
91%
nd
90%



OR Quart 2
>1.0
nd
>1.0



p Value
<0.98
nd
<0.98



95% CI of
>0.062
nd
>0.062



OR Quart 2
na
nd
na



OR Quart 3
>0
nd
>0



p Value
<na
nd
<na



95% CI of
>na
nd
>na



OR Quart 3
na
nd
na



OR Quart 4
>1.1
nd
>1.1



p Value
<0.97
nd
<0.96



95% CI of
>0.064
nd
>0.064



OR Quart 4
na
nd
na











Resistin

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
15900
44200
15900
26500
15900
35600



Average
20800
70900
20800
44000
20800
35000



Stdev
16800
57700
16800
48800
16800
5010



p (t-test)

4.7E−10

0.0013

0.060



Min
1550
10900
1550
7640
1550
27500



Max
135000
142000
135000
141000
135000
41300



n (Samp)
489
5
489
6
489
5



n (Patient)
218
5
218
6
218
5



sCr only



Median
nd
nd
16400
9850
16400
35600



Average
nd
nd
22400
9850
22400
30600



Stdev
nd
nd
20800
3120
20800
9810



p (t-test)
nd
nd

0.39

0.50



Min
nd
nd
1550
7640
1550
19300



Max
nd
nd
150000
12100
150000
36900



n (Samp)
nd
nd
503
2
503
3



n (Patient)
nd
nd
224
2
224
3



UO only



Median
16800
121000
16800
40800
nd
nd



Average
21500
105000
21500
55200
nd
nd



Stdev
16800
47600
16800
48600
nd
nd



p (t-test)

2.8E−20

1.7E−5
nd
nd



Min
1620
34800
1620
20000
nd
nd



Max
135000
142000
135000
141000
nd
nd



n (Samp)
489
4
489
5
nd
nd



n (Patient)
204
4
204
5
nd
nd















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.81
nd
0.95
0.68
0.28
0.82
0.82
0.74
nd


SE
0.12
nd
0.074
0.12
0.21
0.11
0.11
0.17
nd


p
0.0080
nd
1.2E−9
0.14
0.29
0.0046
0.0048
0.15
nd


nCohort 1
489
nd
489
489
503
489
489
503
nd


nCohort 2
5
nd
4
6
2
5
5
3
nd


Cutoff 1
34700
nd
118000
19900
7600
31900
33400
19300
nd


Sens 1
80%
nd
75%
83%
100% 
80%
80%
100% 
nd


Spec 1
83%
nd
100% 
58%
19%
78%
81%
56%
nd


Cutoff 2
34700
nd
34700
19900
7600
31900
33400
19300
nd


Sens 2
80%
nd
100% 
83%
100% 
80%
80%
100% 
nd


Spec 2
83%
nd
81%
58%
19%
78%
81%
56%
nd


Cutoff 3
10700
nd
34700
7600
7600
19900
27400
19300
nd


Sens 3
100% 
nd
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 3
32%
nd
81%
20%
19%
56%
73%
56%
nd


Cutoff 4
25100
nd
26600
25100
26600
26600
25100
26600
nd


Sens 4
80%
nd
100% 
50%
 0%
80%
100% 
67%
nd


Spec 4
70%
nd
70%
70%
70%
70%
70%
70%
nd


Cutoff 5
32300
nd
33900
32300
34000
33900
32300
34000
nd


Sens 5
80%
nd
100% 
33%
 0%
60%
80%
67%
nd


Spec 5
80%
nd
80%
80%
80%
80%
80%
80%
nd


Cutoff 6
42300
nd
43300
42300
44000
43300
42300
44000
nd


Sens 6
60%
nd
75%
33%
 0%
20%
 0%
 0%
nd


Spec 6
90%
nd
90%
90%
90%
90%
90%
90%
nd


OR Quart 2
>1.0
nd
>0
0
>0
>0
>0
>0
nd


p Value
<1.0
nd
<na
na
<na
<na
<na
<na
nd


95% CI of
>0.062
nd
>na
na
>na
>na
>na
>na
nd


OR Quart 2
na
nd
na
na
na
na
na
na
nd


OR Quart 3
>0
nd
>0
2.0
>1.0
>1.0
>1.0
>1.0
nd


p Value
<na
nd
<na
0.57
<0.99
<1.00
<1.00
<1.00
nd


95% CI of
>na
nd
>na
0.18
>0.063
>0.062
>0.062
>0.062
nd


OR Quart 3
na
nd
na
22
na
na
na
na
nd


OR Quart 4
>4.1
nd
>4.1
3.0
>1.0
>4.1
>4.1
>2.0
nd


p Value
<0.21
nd
<0.21
0.34
<0.99
<0.21
<0.21
<0.57
nd


95% CI of
>0.45
nd
>0.45
0.31
>0.063
>0.45
>0.45
>0.18
nd


OR Quart 4
na
nd
na
29
na
na
na
na
nd










Parathyroid hormone

















0 hr prior to AKI stage

24 hr prior to AKI stage

48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
30.5
63.8
30.5
72.0
30.5
41.5



Average
45.7
131
45.7
72.0
45.7
51.0



Stdev
54.2
110
54.2
53.3
54.2
43.3



p (t-test)

6.5E−5

0.24

0.80



Min
2.59
43.1
2.59
15.7
2.59
12.7



Max
506
302
506
132
506
142



n (Samp)
460
7
460
6
460
7



n (Patient)
183
7
183
6
183
7



sCr only



Median
nd
nd
30.9
62.9
30.9
43.3



Average
nd
nd
48.7
62.9
48.7
62.4



Stdev
nd
nd
58.6
61.1
58.6
54.3



p (t-test)
nd
nd

0.73

0.64



Min
nd
nd
2.59
19.7
2.59
20.9



Max
nd
nd
506
106
506
142



n (Samp)
nd
nd
476
2
476
4



n (Patient)
nd
nd
189
2
189
4



UO only



Median
30.6
166
30.6
54.2
30.6
36.7



Average
46.2
167
46.2
72.0
46.2
36.7



Stdev
54.3
139
54.3
51.4
54.3
33.9



p (t-test)

1.6E−5

0.29

0.80



Min
2.59
35.7
2.59
15.7
2.59
12.7



Max
506
302
506
132
506
60.6



n (Samp)
458
4
458
5
458
2



n (Patient)
174
4
174
5
174
2















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.86
nd
0.85
0.65
0.59
0.69
0.59
0.65
0.46


SE
0.090
nd
0.12
0.12
0.21
0.13
0.11
0.15
0.21


p
7.0E−5
nd
0.0047
0.24
0.68
0.16
0.45
0.32
0.83


nCohort 1
460
nd
458
460
476
458
460
476
458


nCohort 2
7
nd
4
6
2
5
7
4
2


Cutoff 1
58.9
nd
58.9
19.7
19.7
37.7
30.0
37.4
12.3


Sens 1
71%
nd
75%
83%
100% 
80%
71%
75%
100% 


Spec 1
80%
nd
81%
27%
27%
62%
48%
61%
10%


Cutoff 2
53.0
nd
35.7
19.7
19.7
37.7
20.9
20.9
12.3


Sens 2
86%
nd
100% 
83%
100% 
80%
86%
100% 
100% 


Spec 2
77%
nd
60%
27%
27%
62%
31%
31%
10%


Cutoff 3
43.1
nd
35.7
15.5
19.7
15.5
12.3
20.9
12.3


Sens 3
100% 
nd
100% 
100% 
100% 
100% 
100% 
100% 
100% 


Spec 3
69%
nd
60%
17%
27%
16%
11%
31%
10%


Cutoff 4
43.3
nd
43.3
43.3
44.8
43.3
43.3
44.8
43.3


Sens 4
86%
nd
75%
50%
50%
60%
43%
50%
50%


Spec 4
70%
nd
70%
70%
70%
70%
70%
70%
70%


Cutoff 5
58.8
nd
58.6
58.8
61.9
58.6
58.8
61.9
58.6


Sens 5
71%
nd
75%
50%
50%
40%
29%
25%
50%


Spec 5
80%
nd
80%
80%
80%
80%
80%
80%
80%


Cutoff 6
88.8
nd
91.5
88.8
100
91.5
88.8
100
91.5


Sens 6
43%
nd
50%
50%
50%
40%
14%
25%
 0%


Spec 6
90%
nd
90%
90%
90%
90%
90%
90%
90%


OR Quart 2
>0
nd
>0
0.99
>1.0
0
2.0
>1.0
0


p Value
<na
nd
<na
1.00
<1.0
na
0.57
<1.00
na


95% CI of
>na
nd
>na
0.061
>0.062
na
0.18
>0.062
na


OR Quart 2
na
nd
na
16
na
na
22
na
na


OR Quart 3
>1.0
nd
>1.0
1.0
>0
0.99
0.99
>2.0
0


p Value
<1.0
nd
<1.00
1.0
<na
1.00
1.00
<0.56
na


95% CI of
>0.062
nd
>0.062
0.062
>na
0.061
0.061
>0.18
na


OR Quart 3
na
nd
na
16
na
16
16
na
na


OR Quart 4
>6.3
nd
>3.1
3.0
>1.0
3.0
3.0
>1.0
1.0


p Value
<0.092
nd
<0.34
0.34
<1.0
0.34
0.34
<1.00
1.0


95% CI of
>0.74
nd
>0.31
0.31
>0.062
0.31
0.31
>0.062
0.062


OR Quart 4
na
nd
na
30
na
30
30
na
16










Serum albumin













24 hr prior to AKI stage













Cohort 1
Cohort 2







sCr or UO



Median
1.89E7
1.54E7



Average
1.93E7
1.54E7



Stdev
6330000
1.17E7



p (t-test)

0.39



Min
5860000
7090000



Max
3.44E7
2.36E7



n (Samp)
124
2



n (Patient)
101
2



UO only



Median
1.89E7
1.54E7



Average
1.93E7
1.54E7



Stdev
6320000
1.17E7



p (t-test)

0.39



Min
5860000
7090000



Max
3.44E7
2.36E7



n (Samp)
108
2



n (Patient)
85
2













24 hr prior to AKI stage













sCr or UO
sCr only
UO only







AUC
0.40
nd
0.41



SE
0.21
nd
0.21



p
0.65
nd
0.67



nCohort 1
124
nd
108



nCohort 2
2
nd
2



Cutoff 1
6690000
nd
6690000



Sens 1
100% 
nd
100% 



Spec 1
 2%
nd
 3%



Cutoff 2
6690000
nd
6690000



Sens 2
100% 
nd
100% 



Spec 2
 2%
nd
 3%



Cutoff 3
6690000
nd
6690000



Sens 3
100% 
nd
100% 



Spec 3
 2%
nd
 3%



Cutoff 4
2.19E7
nd
2.23E7



Sens 4
50%
nd
50%



Spec 4
70%
nd
71%



Cutoff 5
2.42E7
nd
2.41E7



Sens 5
 0%
nd
 0%



Spec 5
81%
nd
81%



Cutoff 6
2.79E7
nd
2.78E7



Sens 6
 0%
nd
 0%



Spec 6
90%
nd
91%



OR Quart 2
0
nd
0



p Value
na
nd
na



95% CI of
na
nd
na



OR Quart 2
na
nd
na



OR Quart 3
0
nd
0



p Value
na
nd
na



95% CI of
na
nd
na



OR Quart 3
na
nd
na



OR Quart 4
1.0
nd
1.0



p Value
0.98
nd
0.98



95% CI of
0.062
nd
0.062



OR Quart 4
17
nd
17











Cortisol
















0 hr prior to AKI stage

24 hr prior to AKI stage
48 hr prior to AKI stage

















Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2







sCr or UO



Median
105
124
105
211
105
151



Average
218
155
218
385
218
161



Stdev
331
110
331
404
331
113



p (t-test)

0.67

0.32

0.73



Min
1.22E−5
44.1
1.22E−5
135
1.22E−5
42.7



Max
1500
325
1500
983
1500
302



n (Samp)
362
5
362
4
362
4



n (Patient)
119
5
119
4
119
4



sCr only



Median
nd
nd
106
159
106
198



Average
nd
nd
221
159
221
179



Stdev
nd
nd
330
178
330
133



p (t-test)
nd
nd

0.79

0.83



Min
nd
nd
1.22E−5
33.2
1.22E−5
37.9



Max
nd
nd
1500
284
1500
302



n (Samp)
nd
nd
373
2
373
3



n (Patient)
nd
nd
122
2
122
3



UO only



Median
103
215
103
135
nd
nd



Average
218
210
218
405
nd
nd



Stdev
330
123
330
501
nd
nd



p (t-test)

0.96

0.33
nd
nd



Min
1.22E−5
84.8
1.22E−5
96.1
nd
nd



Max
1500
325
1500
983
nd
nd



n (Samp)
378
4
378
3
nd
nd



n (Patient)
121
4
121
3
nd
nd















0 hr prior to AKI stage
24 hr prior to AKI stage
48 hr prior to AKI stage

















sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only
sCr or UO
sCr only
UO only





AUC
0.56
nd
0.67
0.75
0.51
0.67
0.58
0.59
nd


SE
0.13
nd
0.15
0.14
0.21
0.17
0.15
0.17
nd


p
0.63
nd
0.26
0.080
0.96
0.32
0.60
0.59
nd


nCohort 1
362
nd
378
362
373
378
362
373
nd


nCohort 2
5
nd
4
4
2
3
4
3
nd


Cutoff 1
84.6
nd
120
138
33.0
95.9
103
37.6
nd


Sens 1
80%
nd
75%
75%
100% 
100% 
75%
100% 
nd


Spec 1
42%
nd
57%
63%
20%
47%
50%
22%
nd


Cutoff 2
84.6
nd
84.6
133
33.0
95.9
41.7
37.6
nd


Sens 2
80%
nd
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 2
42%
nd
42%
61%
20%
47%
24%
22%
nd


Cutoff 3
44.1
nd
84.6
133
33.0
95.9
41.7
37.6
nd


Sens 3
100% 
nd
100% 
100% 
100% 
100% 
100% 
100% 
nd


Spec 3
25%
nd
42%
61%
20%
47%
24%
22%
nd


Cutoff 4
170
nd
170
170
173
170
170
173
nd


Sens 4
40%
nd
50%
50%
50%
33%
50%
67%
nd


Spec 4
70%
nd
70%
70%
70%
70%
70%
70%
nd


Cutoff 5
235
nd
246
235
253
246
235
253
nd


Sens 5
20%
nd
50%
50%
50%
33%
25%
33%
nd


Spec 5
80%
nd
80%
80%
80%
80%
80%
80%
nd


Cutoff 6
675
nd
675
675
704
675
675
704
nd


Sens 6
 0%
nd
 0%
25%
 0%
33%
 0%
 0%
nd


Spec 6
90%
nd
90%
90%
90%
90%
90%
90%
nd


OR Quart 2
>2.0
nd
>1.0
>0
0
>1.0
0.99
0
nd


p Value
<0.57
nd
<1.0
<na
na
<0.99
0.99
na
nd


95% CI of
>0.18
nd
>0.062
>na
na
>0.062
0.061
na
nd


OR Quart 2
na
nd
na
na
na
na
16
na
nd


OR Quart 3
>2.0
nd
>1.0
>2.0
0
>1.0
1.0
1.0
nd


p Value
<0.57
nd
<0.99
<0.56
na
<0.99
1.0
1.0
nd


95% CI of
>0.18
nd
>0.062
>0.18
na
>0.062
0.062
0.062
nd


OR Quart 3
na
nd
na
na
na
na
16
16
nd


OR Quart 4
>1.0
nd
>2.0
>2.0
0.99
>1.0
0.99
1.0
nd


p Value
<1.0
nd
<0.57
<0.57
0.99
<1.0
0.99
1.0
nd


95% CI of
>0.062
nd
>0.18
>0.18
0.061
>0.062
0.061
0.062
nd


OR Quart 4
na
nd
na
na
16
na
16
16
nd
















TABLE 11





Comparison of marker levels in enroll urine samples collected from


Cohort 1 (patients that did not progress beyond RIFLE stage 0 or R within 48 hrs) and in


enroll urine samples collected from Cohort 2 (subjects reaching RIFLE stage I or F within


48 hrs). Enroll samples from patients already at RIFLE stage I or F were included in Cohort 2.







Serum amyloid A protein














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
1.16
1.36
1.22
1.01
1.15
1.68


Average
18.3
118
46.3
1.18
17.6
135


Stdev
152
546
315
0.548
148
583


p (t-test)

0.053

0.69

0.029


Min
0.000420
0.385
0.000420
0.538
0.000420
0.385


Max
1790
2680
2680
2.03
1790
2680


n (Samp)
139
47
174
8
145
41


n (Patient)
139
47
174
8
145
41












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.57
0.43
0.59



SE
0.049
0.11
0.052



p
0.15
0.53
0.085



nCohort 1
139
174
145



nCohort 2
47
8
41



Cutoff 1
0.908
0.974
0.908



Sens 1
70%
75%
71%



Spec 1
39%
40%
39%



Cutoff 2
0.763
0.764
0.763



Sens 2
81%
88%
80%



Spec 2
29%
28%
28%



Cutoff 3
0.565
0.529
0.660



Sens 3
91%
100% 
90%



Spec 3
19%
15%
25%



Cutoff 4
1.82
2.09
1.82



Sens 4
40%
 0%
41%



Spec 4
71%
70%
70%



Cutoff 5
3.34
4.00
3.08



Sens 5
26%
 0%
32%



Spec 5
81%
80%
80%



Cutoff 6
19.7
19.7
14.2



Sens 6
 9%
 0%
12%



Spec 6
91%
90%
90%



OR Quart 2
1.8
>2.1
1.5



p Value
0.24
<0.54
0.45



95% CI of
0.67
>0.19
0.52



OR Quart 2
4.9
na
4.4



OR Quart 3
1.7
>5.6
1.5



p Value
0.31
<0.12
0.42



95% CI of
0.61
>0.63
0.53



OR Quart 3
4.6
na
4.5



OR Quart 4
2.0
>1.0
2.4



p Value
0.16
<0.98
0.098



95% CI of
0.75
>0.063
0.85



OR Quart 4
5.4
na
6.5











Tissue-type plasminogen activator














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.135
0.0624
0.0624
0.00567
0.135
0.0624


Average
19.1
27.1
20.9
20.0
19.4
27.4


Stdev
50.3
76.5
58.9
47.5
50.3
79.7


p (t-test)

0.42

0.97

0.44


Min
0.00252
0.00252
0.00252
0.00252
0.00252
0.00252


Max
401
423
423
137
401
423


n (Samp)
139
47
174
8
145
41


n (Patient)
139
47
174
8
145
41












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.51
0.45
0.52



SE
0.049
0.11
0.052



p
0.78
0.62
0.70



nCohort 1
139
174
145



nCohort 2
47
8
41



Cutoff 1
0.00564
0.00564
0.00564



Sens 1
79%
75%
78%



Spec 1
32%
30%
32%



Cutoff 2
0.00503
0.00314
0.00503



Sens 2
85%
88%
85%



Spec 2
27%
14%
26%



Cutoff 3
0.00314
0
0.00314



Sens 3
94%
100% 
93%



Spec 3
17%
 0%
16%



Cutoff 4
10.1
8.60
10.1



Sens 4
30%
38%
29%



Spec 4
71%
70%
70%



Cutoff 5
22.6
21.6
22.1



Sens 5
17%
12%
17%



Spec 5
81%
80%
80%



Cutoff 6
52.5
48.8
52.5



Sens 6
11%
12%
10%



Spec 6
91%
90%
90%



OR Quart 2
2.3
2.1
3.4



p Value
0.078
0.55
0.021



95% CI of
0.91
0.18
1.2



OR Quart 2
6.0
24
9.8



OR Quart 3
1.1
3.1
1.6



p Value
0.80
0.33
0.40



95% CI of
0.42
0.31
0.53



OR Quart 3
3.1
31
5.0



OR Quart 4
1.3
2.1
1.8



p Value
0.65
0.55
0.30



95% CI of
0.47
0.18
0.60



OR Quart 4
3.4
24
5.4











Protein S100-B














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
0.0871
23.8
0.0871
23.8
0.0871
24.6


Average
7.12
218
31.1
201
6.46
245


Stdev
15.4
427
168
325
15.1
449


p (t-test)

7.0E−4

0.11

7.6E−4


Min
0.0517
0.755
0.0517
3.13
0.0517
0.755


Max
88.3
1240
1240
576
88.3
1240


n (Samp)
49
9
55
3
42
8


n (Patient)
49
9
55
3
42
8












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.83
0.83
0.85



SE
0.088
0.15
0.089



p
2.3E−4
0.028
1.1E−4



nCohort 1
49
55
42



nCohort 2
9
3
8



Cutoff 1
1.55
1.55
3.13



Sens 1
78%
100% 
75%



Spec 1
67%
64%
69%



Cutoff 2
0.755
1.55
0.755



Sens 2
89%
100% 
88%



Spec 2
61%
64%
60%



Cutoff 3
0.174
1.55
0.0871



Sens 3
100% 
100% 
100% 



Spec 3
59%
64%
57%



Cutoff 4
6.21
6.21
6.21



Sens 4
56%
67%
62%



Spec 4
73%
71%
76%



Cutoff 5
12.4
12.4
10.3



Sens 5
56%
67%
62%



Spec 5
84%
80%
81%



Cutoff 6
23.8
26.8
14.0



Sens 6
44%
33%
62%



Spec 6
92%
91%
90%



OR Quart 2
>0
>0
>0



p Value
<na
<na
<na



95% CI of
>na
>na
>na



OR Quart 2
na
na
na



OR Quart 3
>5.6
>1.1
>4.0



p Value
<0.15
<0.96
<0.26



95% CI of
>0.54
>0.061
>0.35



OR Quart 3
na
na
na



OR Quart 4
>7.0
>2.2
>7.5



p Value
<0.097
<0.55
<0.090



95% CI of
>0.71
>0.17
>0.73



OR Quart 4
na
na
na











Resistin














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
40200
40000
40200
37800
40200
40300


Average
46900
47100
47200
42200
46700
48700


Stdev
26700
24900
26400
23500
26400
25600


p (t-test)

0.96

0.38

0.54


Min
1230
863
863
4100
1230
863


Max
104000
100000
104000
100000
104000
100000


n (Samp)
344
99
415
23
349
86


n (Patient)
344
99
415
23
349
86












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.51
0.45
0.52



SE
0.033
0.063
0.035



p
0.79
0.45
0.49



nCohort 1
344
415
349



nCohort 2
99
23
86



Cutoff 1
32600
29400
32600



Sens 1
71%
74%
71%



Spec 1
35%
26%
35%



Cutoff 2
27100
26000
27800



Sens 2
81%
83%
80%



Spec 2
23%
20%
24%



Cutoff 3
22800
20500
23400



Sens 3
91%
91%
91%



Spec 3
17%
12%
18%



Cutoff 4
55100
55500
55100



Sens 4
28%
22%
30%



Spec 4
70%
70%
70%



Cutoff 5
67900
68700
66800



Sens 5
19%
 9%
22%



Spec 5
80%
80%
80%



Cutoff 6
100000
100000
100000



Sens 6
 0%
 0%
 0%



Spec 6
99%
100% 
99%



OR Quart 2
1.3
2.4
1.5



p Value
0.35
0.20
0.25



95% CI of
0.72
0.62
0.76



OR Quart 2
2.5
9.7
2.9



OR Quart 3
1.2
2.4
1.2



p Value
0.54
0.21
0.62



95% CI of
0.64
0.61
0.60



OR Quart 3
2.3
9.6
2.4



OR Quart 4
1.0
2.1
1.3



p Value
0.89
0.31
0.50



95% CI of
0.54
0.51
0.63



OR Quart 4
2.0
8.5
2.5











Parathyroid hormone














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
17.2
16.5
17.1
22.7
17.4
15.8


Average
22.7
24.2
22.9
25.6
23.0
23.1


Stdev
24.7
24.5
24.7
25.0
24.3
23.8


p (t-test)

0.55

0.58

0.97


Min
0.000320
0.000831
0.000320
0.00185
0.000320
0.000831


Max
302
128
302
128
302
113


n (Samp)
410
126
501
28
407
106


n (Patient)
410
126
501
28
407
106












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.50
0.55
0.47



SE
0.029
0.057
0.032



p
1.00
0.40
0.41



nCohort 1
410
501
407



nCohort 2
126
28
106



Cutoff 1
7.41
10.7
6.59



Sens 1
71%
71%
71%



Spec 1
25%
35%
21%



Cutoff 2
5.21
6.85
4.13



Sens 2
80%
82%
80%



Spec 2
19%
25%
13%



Cutoff 3
0.659
5.29
0.562



Sens 3
90%
93%
91%



Spec 3
 2%
20%
 1%



Cutoff 4
25.6
26.8
26.7



Sens 4
37%
39%
34%



Spec 4
70%
70%
70%



Cutoff 5
33.9
34.5
34.3



Sens 5
25%
21%
23%



Spec 5
80%
80%
80%



Cutoff 6
48.7
51.7
49.6



Sens 6
17%
 4%
16%



Spec 6
90%
90%
90%



OR Quart 2
0.66
0.85
0.61



p Value
0.15
0.78
0.12



95% CI of
0.37
0.28
0.33



OR Quart 2
1.2
2.6
1.1



OR Quart 3
0.75
1.2
0.76



p Value
0.32
0.79
0.38



95% CI of
0.43
0.41
0.42



OR Quart 3
1.3
3.3
1.4



OR Quart 4
0.96
0.99
1.1



p Value
0.89
0.99
0.74



95% CI of
0.56
0.34
0.62



OR Quart 4
1.7
2.9
1.9











Serum albumin














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
24200
57800
27000
71000
25700
56600


Average
62800
207000
89100
226000
69500
204000


Stdev
148000
376000
211000
439000
176000
359000


p

2.2E−8

0.0054

1.0E−6


(t-test)


Min
1.10
1.10
1.10
2010
1.10
1.10


Max
1650000
1830000
1780000
1830000
1830000
1780000


n
336
99
407
23
341
86


(Samp)


n)
336
99
407
23
341
86


(Patient












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.66
0.69
0.64



SE
0.033
0.063
0.035



p
1.5E−6
0.0031
1.1E−4



nCohort 1
336
407
341



nCohort 2
99
23
86



Cutoff 1
26200
42600
19900



Sens 1
71%
74%
71%



Spec 1
53%
63%
43%



Cutoff 2
13100
17100
12900



Sens 2
81%
83%
80%



Spec 2
31%
39%
29%



Cutoff 3
4700
11700
4700



Sens 3
91%
91%
91%



Spec 3
13%
26%
13%



Cutoff 4
48800
57800
52800



Sens 4
56%
52%
53%



Spec 4
70%
70%
70%



Cutoff 5
71300
87300
73900



Sens 5
42%
43%
41%



Spec 5
80%
80%
80%



Cutoff 6
114000
182000
123000



Sens 6
33%
22%
30%



Spec 6
90%
90%
90%



OR Quart 2
1.2
1.5
1.2



p Value
0.59
0.66
0.58



95% CI of
0.58
0.25
0.58



OR Quart 2
2.6
9.2
2.7



OR Quart 3
1.8
3.7
1.5



p Value
0.12
0.11
0.28



95% CI of
0.86
0.75
0.72



OR Quart 3
3.6
18
3.2



OR Quart 4
3.9
6.0
3.2



p Value
6.8E−5
0.022
0.0010



95% CI of
2.0
1.3
1.6



OR Quart 4
7.6
28
6.4











Cortisol














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
181
209
192
183
190
203


Average
322
375
330
355
331
354


Stdev
348
367
350
392
354
350


p (t-test)

0.10

0.67

0.52


Min
1.43
14.8
1.43
19.8
1.43
14.8


Max
1500
1500
1500
1490
1500
1500


n (Samp)
624
148
727
36
555
125


n (Patient)
624
148
727
36
555
125












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.55
0.50
0.53



SE
0.027
0.049
0.029



p
0.082
0.96
0.33



nCohort 1
624
727
555



nCohort 2
148
36
125



Cutoff 1
113
97.2
115



Sens 1
70%
72%
70%



Spec 1
33%
27%
33%



Cutoff 2
84.9
76.0
84.9



Sens 2
80%
81%
80%



Spec 2
25%
22%
24%



Cutoff 3
53.1
29.6
62.1



Sens 3
91%
92%
90%



Spec 3
16%
 7%
17%



Cutoff 4
344
351
352



Sens 4
36%
33%
32%



Spec 4
70%
70%
70%



Cutoff 5
531
589
537



Sens 5
29%
25%
26%



Spec 5
80%
80%
80%



Cutoff 6
881
881
896



Sens 6
11%
11%
 9%



Spec 6
90%
90%
90%



OR Quart 2
1.2
0.69
1.2



p Value
0.50
0.46
0.56



95% CI of
0.71
0.26
0.67



OR Quart 2
2.0
1.8
2.1



OR Quart 3
1.2
1.0
1.2



p Value
0.59
1.0
0.56



95% CI of
0.68
0.41
0.67



OR Quart 3
2.0
2.5
2.1



OR Quart 4
1.6
0.90
1.4



p Value
0.057
0.82
0.21



95% CI of
0.98
0.36
0.82



OR Quart 4
2.7
2.3
2.5

















TABLE 12





Comparison of marker levels in enroll EDTA samples collected


from Cohort 1 (patients that did not progress beyond RIFLE stage 0 or R within 48 hrs)


and in enroll EDTA samples collected from Cohort 2 (subjects reaching RIFLE stage I or


F within 48 hrs). Enroll samples from patients already at stage I or F were included in


Cohort 2.







Serum amyloid A protein














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
39800
56600
40800
37400
39800
61200


Average
569000
597000
582000
37400
569000
627000


Stdev
807000
842000
816000
20600
807000
854000


p (t-test)

0.89

0.35

0.78


Min
559
4320
559
22900
559
4320


Max
2630000
2630000
2630000
52000
2630000
2630000


n (Samp)
95
20
111
2
95
19


n (Patient)
95
20
111
2
95
19












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.55
0.39
0.57



SE
0.072
0.21
0.074



p
0.49
0.60
0.38



nCohort 1
95
111
95



nCohort 2
20
2
19



Cutoff 1
31300
22400
31300



Sens 1
70%
100% 
74%



Spec 1
39%
22%
39%



Cutoff 2
26200
22400
26200



Sens 2
80%
100% 
84%



Spec 2
29%
22%
29%



Cutoff 3
22400
22400
21200



Sens 3
90%
100% 
95%



Spec 3
24%
22%
23%



Cutoff 4
893000
893000
893000



Sens 4
20%
 0%
21%



Spec 4
76%
77%
76%



Cutoff 5
1340000
1340000
1340000



Sens 5
10%
 0%
11%



Spec 5
92%
91%
92%



Cutoff 6
1340000
1340000
1340000



Sens 6
10%
 0%
11%



Spec 6
92%
91%
92%



OR Quart 2
1.7
>1.1
2.7



p Value
0.48
<0.96
0.26



95% CI of
0.37
>0.064
0.48



OR Quart 2
8.1
na
15



OR Quart 3
3.2
>0
5.2



p Value
0.12
<na
0.051



95% CI of
0.75
>na
0.99



OR Quart 3
14
na
27



OR Quart 4
1.3
>1.1
2.1



p Value
0.72
<0.96
0.42



95% CI of
0.27
>0.064
0.35



OR Quart 4
6.6
na
12











Tissue-type plasminogen activator














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
9450
9840
9690
3080
9420
10400


Average
11100
9120
10800
3080
10900
9370


Stdev
9560
4640
8980
1910
9580
4630


p (t-test)

0.38

0.23

0.49


Min
0.840
1070
0.840
1730
0.840
1070


Max
70800
16800
70800
4430
70800
16800


n (Samp)
95
20
111
2
95
19


n (Patient)
95
20
111
2
95
19












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.48
0.12
0.50



SE
0.072
0.16
0.073



p
0.76
0.015
0.97



nCohort 1
95
111
95



nCohort 2
20
2
19



Cutoff 1
7560
1510
7560



Sens 1
70%
100% 
74%



Spec 1
40%
 6%
41%



Cutoff 2
3920
1510
3150



Sens 2
80%
100% 
84%



Spec 2
17%
 6%
12%



Cutoff 3
2550
1510
1510



Sens 3
90%
100% 
95%



Spec 3
 8%
 6%
 6%



Cutoff 4
12900
12700
12700



Sens 4
20%
 0%
26%



Spec 4
71%
70%
71%



Cutoff 5
14900
14300
14300



Sens 5
 5%
 0%
16%



Spec 5
80%
80%
80%



Cutoff 6
20500
18100
20500



Sens 6
 0%
 0%
 0%



Spec 6
91%
90%
91%



OR Quart 2
1.6
>0
1.2



p Value
0.49
<na
0.76



95% CI of
0.41
>na
0.30



OR Quart 2
6.5
na
5.2



OR Quart 3
1.3
>0
1.6



p Value
0.72
<na
0.49



95% CI of
0.31
>na
0.41



OR Quart 3
5.4
na
6.6



OR Quart 4
1.4
>2.2
0.96



p Value
0.67
<0.52
0.96



95% CI of
0.32
>0.19
0.22



OR Quart 4
5.7
na
4.3











Protein S100-B















sCr or UO

UO only















Cohort 1
Cohort 2
Cohort 1
Cohort 2







Median
0.134
5.77
1.73
5.77



Average
15.8
21.6
17.2
21.6



Stdev
33.3
46.0
35.4
46.0



p (t-test)

0.66

0.75



Min
0.0774
0.0774
0.0774
0.0774



Max
202
143
202
143



n (Samp)
46
9
40
9



n (Patient)
46
9
40
9














At Enrollment













sCr or UO
UO only







AUC
0.53
0.52



SE
0.11
0.11



p
0.80
0.88



nCohort 1
46
40



nCohort 2
9
9



Cutoff 1
0.0774
0.0774



Sens 1
78%
78%



Spec 1
24%
22%



Cutoff 2
0
0



Sens 2
100% 
100% 



Spec 2
 0%
 0%



Cutoff 3
0
0



Sens 3
100% 
100% 



Spec 3
 0%
 0%



Cutoff 4
14.2
12.9



Sens 4
22%
33%



Spec 4
74%
70%



Cutoff 5
25.7
25.7



Sens 5
11%
11%



Spec 5
80%
80%



Cutoff 6
35.5
35.5



Sens 6
11%
11%



Spec 6
91%
90%



OR Quart 2
0.42
0.27



p Value
0.51
0.29



95% CI of
0.034
0.024



OR Quart 2
5.3
3.1



OR Quart 3
2.2
1.0



p Value
0.42
1.0



95% CI of
0.33
0.16



OR Quart 3
15
6.3



OR Quart 4
0.92
0.55



p Value
0.94
0.55



95% CI of
0.11
0.074



OR Quart 4
7.7
4.0











Resistin














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
17500
28600
18900
34100
18100
29700


Average
23000
32700
24500
34100
23600
32900


Stdev
20300
24500
21600
9460
20500
24900


p (t-test)

0.022

0.53

0.034


Min
1550
5390
1550
27400
1950
5390


Max
135000
141000
141000
40800
135000
141000


n (Samp)
141
30
166
2
135
29


n (Patient)
141
30
166
2
135
29












At Enrollment













sCr or UO
sCr only
UO only







AUC
0.67
0.76
0.66



SE
0.058
0.20
0.059



p
0.0032
0.20
0.0073



nCohort 1
141
166
135



nCohort 2
30
2
29



Cutoff 1
22200
27100
18400



Sens 1
70%
100% 
72%



Spec 1
58%
67%
52%



Cutoff 2
17800
27100
14800



Sens 2
80%
100% 
83%



Spec 2
51%
67%
44%



Cutoff 3
12900
27100
11200



Sens 3
90%
100% 
93%



Spec 3
39%
67%
34%



Cutoff 4
27100
30700
28200



Sens 4
57%
50%
52%



Spec 4
70%
70%
70%



Cutoff 5
35100
36200
35500



Sens 5
37%
50%
34%



Spec 5
80%
80%
80%



Cutoff 6
45600
47400
46300



Sens 6
17%
 0%
17%



Spec 6
90%
90%
90%



OR Quart 2
3.9
>0
4.0



p Value
0.10
<na
0.096



95% CI of
0.76
>na
0.78



OR Quart 2
20
na
21



OR Quart 3
5.3
>1.0
5.5



p Value
0.041
<0.99
0.037



95% CI of
1.1
>0.062
1.1



OR Quart 3
26
na
27



OR Quart 4
7.7
>1.0
7.2



p Value
0.011
<0.99
0.015



95% CI of
1.6
>0.062
1.5



OR Quart 4
37
na
35











Parathyroid hormone














sCr or UO
sCr only
UO only














Cohort 1
Cohort 2
Cohort 1
Cohort 2
Cohort 1
Cohort 2





Median
31.0
63.6
31.5
106
31.2
54.2


Average
47.5
97.6
54.7
117
48.7
99.3


Stdev
51.6
108
67.5
86.4
52.7
116


p (t-test)

3.8E−4

0.021

9.9E−4


Min
6.19
4.55
4.55
43.3
6.19
4.55


Max
275
506
506
296
275
506


n (Samp)
118
29
138
7
114
25


n (Patient)
118
29
138
7
114
25












At Enrollment

















sCr or UO
sCr only
UO only







AUC
0.69
0.84
0.66



SE
0.059
0.095
0.064



p
0.0015
4.2E−4
0.015



nCohort 1
118
138
114



nCohort 2
29
7
25



Cutoff 1
36.0
63.0
31.2



Sens 1
72%
71%
72%



Spec 1
62%
80%
51%



Cutoff 2
27.2
52.4
27.2



Sens 2
83%
86%
80%



Spec 2
43%
73%
43%



Cutoff 3
11.8
42.9
11.8



Sens 3
93%
100% 
92%



Spec 3
 8%
65%
 9%



Cutoff 4
46.3
49.2
47.9



Sens 4
59%
86%
52%



Spec 4
70%
70%
70%



Cutoff 5
55.6
69.1
58.6



Sens 5
52%
57%
48%



Spec 5
81%
80%
81%



Cutoff 6
111
125
111



Sens 6
28%
29%
28%



Spec 6
91%
91%
90%



OR Quart 2
0.97
>0
0.97



p Value
0.97
<na
0.97



95% CI of
0.22
>na
0.22



OR Quart 2
4.2
na
4.2



OR Quart 3
1.5
>2.1
1.2



p Value
0.53
<0.55
0.76



95% CI of
0.40
>0.18
0.31



OR Quart 3
6.0
na
5.1



OR Quart 4
5.5
>5.6
3.9



p Value
0.0068
<0.12
0.033



95% CI of
1.6
>0.62
1.1



OR Quart 4
19
na
14











Serum albumin















sCr or UO

UO only















Cohort 1
Cohort 2
Cohort 1
Cohort 2







Median
2.00E7
2.07E7
2.08E7
2.07E7



Average
2.12E7
1.85E7
2.15E7
1.85E7



Stdev
6730000
4620000
6530000
4620000



p (t-test)

0.23

0.18



Min
8940000
1.07E7
9920000
1.07E7



Max
3.44E7
2.36E7
3.44E7
2.36E7



n (Samp)
46
10
40
10



n (Patient)
46
10
40
10














At Enrollment













sCr or UO
UO only







AUC
0.41
0.39



SE
0.10
0.10



p
0.39
0.30



nCohort 1
46
40



nCohort 2
10
10



Cutoff 1
1.93E7
1.90E7



Sens 1
70%
70%



Spec 1
50%
48%



Cutoff 2
1.42E7
1.42E7



Sens 2
80%
80%



Spec 2
15%
12%



Cutoff 3
1.11E7
1.11E7



Sens 3
90%
90%



Spec 3
 9%
 8%



Cutoff 4
2.48E7
2.42E7



Sens 4
 0%
 0%



Spec 4
72%
70%



Cutoff 5
2.78E7
2.64E7



Sens 5
 0%
 0%



Spec 5
80%
80%



Cutoff 6
3.14E7
3.14E7



Sens 6
 0%
 0%



Spec 6
91%
90%



OR Quart 2
>7.8
>6.5



p Value
<0.081
<0.12



95% CI of
>0.78
>0.61



OR Quart 2
na
na



OR Quart 3
>2.3
>3.9



p Value
<0.51
<0.27



95% CI of
>0.19
>0.35



OR Quart 3
na
na



OR Quart 4
>3.8
>4.3



p Value
<0.27
<0.23



95% CI of
>0.35
>0.39



OR Quart 4
na
na










While the invention has been described and exemplified in sufficient detail for those skilled in this art to make and use it, various alternatives, modifications, and improvements should be apparent without departing from the spirit and scope of the invention. The examples provided herein are representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention. Modifications therein and other uses will occur to those skilled in the art. These modifications are encompassed within the spirit of the invention and are defined by the scope of the claims.


It will be readily apparent to a person skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention.


All patents and publications mentioned in the specification are indicative of the levels of those of ordinary skill in the art to which the invention pertains. All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.


The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.


Other embodiments are set forth within the following claims.

Claims
  • 1. A method for evaluating renal status in a subject, comprising: performing one or more assays configured to detect one or more biomarkers selected from the group consisting of Serum albumin, Protein S100-B, Glial cell line-derived neurotrophic factor, Resistin, Serum amyloid A protein, Hydrocortisone, Parathyroid hormone, and Tissue Plasminogen Activator by introducing a body fluid sample obtained from the subject into an assay instrument which (i) for each analyte binding assay performed, contacts all or a portion of the urine sample with a binding reagent which specifically binds for detection the kidney injury marker which is assayed, (ii) generates to provide one or more assay results indicative of binding of each biomarker which is assayed to its respective binding reagent to provide an assay result; andcorrelating the assay result(s) generated by the assay instrument to the renal status of the subject, wherein said correlation step comprises correlating the assay result(s) to one or more of risk stratification, prognosis, classifying and monitoring of the renal status of the subject.
  • 2. A method according to claim 1, wherein said correlation step comprises correlating the assay result(s) to prognosis of the renal status of the subject.
  • 3. A method according to claim 1, wherein said correlating step comprises assigning a likelihood of one or more future changes in renal status to the subject based on the assay result(s).
  • 4. A method according to claim 3, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF).
  • 5. A method according to claim 1, wherein said assay results comprise at least 2, 3, 4, or 5 of: a measured concentration of Serum albumin,a measured concentration of Protein S100-B,a measured concentration of Glial cell line-derived neurotrophic factor,a measured concentration of Resistin,a measured concentration of Serum amyloid A protein,a measured concentration of Hydrocortisone,a measured concentration of Parathyroid hormone, anda measured concentration of Tissue Plasminogen Activator.
  • 6. A method according to claim 5, wherein a plurality of assay results are combined using a function that converts the plurality of assay results into a single composite result.
  • 7. A method according to claim 3, wherein said one or more future changes in renal status comprise a clinical outcome related to a renal injury suffered by the subject.
  • 8. A method according to claim 3, wherein the likelihood of one or more future changes in renal status is that an event of interest is more or less likely to occur within 30 days of the time at which the body fluid sample is obtained from the subject.
  • 9. A method according to claim 8, wherein the likelihood of one or more future changes in renal status is that an event of interest is more or less likely to occur within a period selected from the group consisting of 21 days, 14 days, 7 days, 5 days, 96 hours, 72 hours, 48 hours, 36 hours, 24 hours, and 12 hours.
  • 10. A method according to claim 5, wherein the subject is selected for evaluation of renal status based on the pre-existence in the subject of one or more known risk factors for prerenal, intrinsic renal, or postrenal ARF.
  • 11. A method according to claim 1, wherein the subject is selected for evaluation of renal status based on an existing diagnosis of one or more of congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, glomerular filtration below the normal range, cirrhosis, serum creatinine above the normal range, sepsis, injury to renal function, reduced renal function, or ARF, or based on undergoing or having undergone major vascular surgery, coronary artery bypass, or other cardiac surgery, or based on exposure to NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin.
  • 12. A method according to claim 1, wherein said correlating step comprises assessing whether or not renal function is improving or worsening in a subject who has suffered from an injury to renal function, reduced renal function, or ARF based on the assay result(s).
  • 13. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of an injury to renal function in said subject.
  • 14. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of reduced renal function in said subject.
  • 15. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of a need for dialysis in said subject.
  • 16. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of acute renal failure in said subject.
  • 17. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of a need for renal replacement therapy in said subject.
  • 18. A method according to claim 1, wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of a need for renal transplantation in said subject.
  • 19. A method according to claim 1, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 72 hours of the time at which the body fluid sample is obtained.
  • 20. A method according to claim 1, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 48 hours of the time at which the body fluid sample is obtained.
  • 21. A method according to claim 1, wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF) within 24 hours of the time at which the body fluid sample is obtained.
  • 22. A method according to claim 1, wherein the subject is in RIFLE stage 0 or R.
  • 23. A method according to claim 22, wherein the subject is in RIFLE stage 0, and said correlating step comprises assigning a likelihood that the subject will reach RIFLE stage R, I or F within 72 hours.
  • 24-27. (canceled)
  • 28. A method according to claim 22, wherein the subject is in RIFLE stage R, and said correlating step comprises assigning a likelihood that the subject will reach RIFLE stage I or F within 72 hours.
  • 29-49. (canceled)
  • 50. A method according to claim 1, wherein the subject is not in acute renal failure.
  • 51-121. (canceled)
  • 122. A method according to claim 1, further comprising treating the patient based on the predetermined subpopulation of individuals to which the patient is assigned, wherein the treatment comprises one or more of initiating renal replacement therapy, withdrawing delivery of compounds that are known to be damaging to the kidney, delaying or avoiding procedures that are known to be damaging to the kidney, and modifying diuretic administration.
Parent Case Info

The present application claims priority to provisional U.S. patent application 61/506,035 filed Jul. 9, 2011, which is hereby incorporated in its entirety including all tables, figures, and claims.

PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/US12/45581 7/5/2012 WO 00 1/20/2014
Provisional Applications (1)
Number Date Country
61506035 Jul 2011 US