Methods and compositions for diagnosis and prognosis of renal injury and renal failure

Abstract

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in sepsis patients . In particular, the invention relates to using assays that detect one or more biomarkers selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase as diagnostic and prognostic biomarker assays of renal injury in the sepsis patient.

We claim: 
     
         1 . A method for evaluating renal status in a sepsis patient, comprising:
 performing one or more assays configured to detect one or more biomarkers selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase on a body fluid sample obtained from the sepsis patient to provide an assay result; and   correlating the assay result(s) to the renal status of the sepsis patient.   
     
     
         2 . A method according to  claim 1 , wherein said correlation step comprises correlating the assay result(s) to one or more of risk stratification, diagnosis, staging, prognosis, classifying and monitoring of the renal status of the sepsis patient. 
     
     
         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 sepsis patient 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 one of  claims 1 - 4 , wherein said assay results comprise at least 2, 3, or 4 of:
 a measured urine or plasma concentration of Insulin-like growth factor-binding protein 7, a measured urine or plasma concentration of Beta-2-glycoprotein 1, a measured urine or plasma concentration of Metalloproteinase inhibitor 2, a measured urine or plasma concentration of Alpha-1 Antitrypsin, a measured urine or plasma concentration of Leukocyte elastase, a measured urine or plasma concentration of Serum Amyloid P Component, a measured urine or plasma concentration of C—X—C motif chemokine 6, a measured urine or plasma concentration of Immunoglobulin A, a measured urine or plasma concentration of Immunoglobulin G subclass I, a measured urine or plasma concentration of C—C motif chemokine 24, a measured urine or plasma concentration of Neutrophil collagenase, a measured urine or plasma concentration of Cathepsin D, a measured urine or plasma concentration of C—X—C motif chemokine 13, a measured urine or plasma concentration of Involucrin, a measured urine or plasma concentration of Interleukin-6 receptor subunit beta, a measured urine or plasma concentration of Hepatocyte Growth Factor, a measured urine or plasma concentration of CXCL-1, a measured urine or plasma concentration of -2, a measured urine or plasma concentration of -3, a measured urine or plasma concentration of Immunoglobulin G subclass II, a measured urine or plasma concentration of Metalloproteinase inhibitor 4, a measured urine or plasma concentration of C—C motif chemokine 18, a measured urine or plasma concentration of Matrilysin, a measured urine or plasma concentration of C—X—C motif chemokine 11, and a measured urine or plasma concentration of Antileukoproteinase.   
     
     
         6 . A method according to one of  claims 1 - 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 sepsis patient. 
     
     
         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 sepsis patient. 
     
     
         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 one of  claims 1 - 5 , wherein the sepsis patient is a severe sepsis patient. 
     
     
         11 . A method according to one of  claims 1 - 5 , wherein the sepsis patient is a septic shock patient. 
     
     
         12 . A method according to one of  claims 1 - 5 , wherein said correlating step comprises assigning a diagnosis of the occurrence or nonoccurrence of one or more of an injury to renal function, reduced renal function, or ARF to the sepsis patient based on the assay result(s). 
     
     
         13 . A method according to one of  claims 1 - 5 , wherein said correlating step comprises assessing whether or not renal function is improving or worsening in a sepsis patient who has suffered from an injury to renal function, reduced renal function, or ARF based on the assay result(s). 
     
     
         14 . A method according to one of  claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of an injury to renal function in said sepsis patient. 
     
     
         15 . A method according to one of  claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of reduced renal function in said sepsis patient. 
     
     
         16 . A method according to one of  claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of acute renal failure in said sepsis patient. 
     
     
         17 . A method according to one of  claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of a need for renal replacement therapy in said sepsis patient. 
     
     
         18 . A method according to one of  claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of a need for renal transplantation in said sepsis patient. 
     
     
         19 . A method according to one of  claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of an injury to renal function in said sepsis patient. 
     
     
         20 . A method according to one of  claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of reduced renal function in said sepsis patient. 
     
     
         21 . A method according to one of  claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of acute renal failure in said sepsis patient. 
     
     
         22 . A method according to one of  claims 1 - 5 , 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 sepsis patient. 
     
     
         23 . A method according to one of  claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of a need for renal transplantation in said sepsis patient. 
     
     
         24 . A method according to one of  claims 1 - 5 , 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. 
     
     
         25 . A method according to one of  claims 1 - 5 , 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. 
     
     
         26 . A method according to one of  claims 1 - 5 , 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. 
     
     
         27 . A method according to one of  claims 1 - 5 , wherein the sepsis patient is in RIFLE stage 0 or R. 
     
     
         28 . A method according to  claim 27 , wherein the sepsis patient is in RIFLE stage 0, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage R, I or F within 72 hours. 
     
     
         29 . A method according to  claim 28 , wherein the sepsis patient is in RIFLE stage 0, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 72 hours. 
     
     
         30 . A method according to  claim 28 , wherein the sepsis patient is in RIFLE stage 0, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 72 hours. 
     
     
         31 . A method according to  claim 27 , wherein the sepsis patient is in RIFLE stage 0 or R, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 72 hours. 
     
     
         32 . A method according to  claim 31 , wherein the sepsis patient is in RIFLE stage 0 or R, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 72 hours. 
     
     
         33 . A method according to  claim 27 , wherein the sepsis patient is in RIFLE stage R, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 72 hours. 
     
     
         34 . A method according to  claim 33 , wherein the sepsis patient is in RIFLE stage R, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 72 hours. 
     
     
         35 . A method according to one of  claims 1 - 5 , wherein the sepsis patient is in RIFLE stage 0, R, or I, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 72 hours. 
     
     
         36 . A method according to  claim 35 , wherein the sepsis patient is in RIFLE stage I, and said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 72 hours. 
     
     
         37 . A method according to  claim 28 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage R, I or F within 48 hours. 
     
     
         38 . A method according to  claim 29 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 48 hours. 
     
     
         39 . A method according to  claim 30 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 48 hours. 
     
     
         40 . A method according to  claim 31 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 48 hours. 
     
     
         41 . A method according to  claim 32 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 48 hours. 
     
     
         42 . A method according to  claim 33 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 48 hours. 
     
     
         43 . A method according to  claim 34 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 48 hours. 
     
     
         44 . A method according to  claim 35 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 48 hours. 
     
     
         45 . A method according to  claim 36 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 48 hours. 
     
     
         46 . A method according to  claim 28 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage R, I or F within 24 hours. 
     
     
         47 . A method according to  claim 29 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 24 hours. 
     
     
         48 . A method according to  claim 30 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 24 hours. 
     
     
         49 . A method according to  claim 31 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 24 hours. 
     
     
         50 . A method according to  claim 32 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 24 hours. 
     
     
         51 . A method according to  claim 33 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage I or F within 24 hours. 
     
     
         52 . A method according to  claim 34 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 24 hours. 
     
     
         53 . A method according to  claim 35 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 24 hours. 
     
     
         54 . A method according to  claim 36 , wherein said correlating step comprises assigning a likelihood that the sepsis patient will reach RIFLE stage F within 24 hours. 
     
     
         55 . A method according to one of  claims 1 - 5 , wherein the sepsis patient is not in acute renal failure. 
     
     
         56 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has not experienced a 1.5-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         57 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has a urine output of at least 0.5 ml/kg/hr over the 6 hours preceding the time at which the body fluid sample is obtained. 
     
     
         58 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has not experienced an increase of 0.3 mg/dL or greater in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         59 . A method according to one of  claims 1 - 5 , wherein the sepsis patient (i) has not experienced a 1.5-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained, (ii) has a urine output of at least 0.5 ml/kg/hr over the 6 hours preceding the time at which the body fluid sample is obtained, and (iii) has not experienced an increase of 0.3 mg/dL or greater in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         60 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has not experienced a 1.5-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         61 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has a urine output of at least 0.5 ml/kg/hr over the 6 hours preceding the time at which the body fluid sample is obtained. 
     
     
         62 . A method according to one of  claims 1 - 5 , wherein the sepsis patient (i) has not experienced a 1.5-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained, (ii) has a urine output of at least 0.5 ml/kg/hr over the 12 hours preceding the time at which the body fluid sample is obtained, and (iii) has not experienced an increase of 0.3 mg/dL or greater in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         63 . A method according to one of  claims 1 - 5 , wherein said correlating step comprises assigning one or more of: a likelihood that within 72 hours the sepsis patient will (i) experience a 1.5-fold or greater increase in serum creatinine (ii) have a urine output of less than 0.5 ml/kg/hr over a 6 hour period, or (iii) experience an increase of 0.3 mg/dL, or greater in serum creatinine. 
     
     
         64 . A method according to  claim 63 , wherein said correlating step comprises assigning one or more of: a likelihood that within 48 hours the sepsis patient will (i) experience a 1.5-fold or greater increase in serum creatinine (ii) have a urine output of less than 0.5 ml/kg/hr over a 6 hour period, or (iii) experience an increase of 0.3 mg/dL or greater in serum creatinine. 
     
     
         65 . A method according to  claim 63 , wherein said correlating step comprises assigning one or more of: a likelihood that within 24 hours the sepsis patient will (i) experience a 1.5-fold or greater increase in serum creatinine (ii) have a urine output of less than 0.5 ml/kg/hr over a 6 hour period, or (iii) experience an increase of 0.3 mg/dL or greater in serum creatinine. 
     
     
         66 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 72 hours the sepsis patient will experience a 1.5-fold or greater increase in serum creatinine. 
     
     
         67 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 72 hours the sepsis patient will have a urine output of less than 0.5 ml/kg/hr over a 6 hour period. 
     
     
         68 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 72 hours the sepsis patient will experience an increase of 0.3 mg/dL or greater in serum creatinine. 
     
     
         69 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 48 hours the sepsis patient will experience a 1.5-fold or greater increase in serum creatinine. 
     
     
         70 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 48 hours the sepsis patient will have a urine output of less than 0.5 ml/kg/hr over a 6 hour period. 
     
     
         71 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 48 hours the sepsis patient will experience an increase of 0.3 mg/dL or greater in serum creatinine. 
     
     
         72 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 24 hours the sepsis patient will experience a 1.5-fold or greater increase in serum creatinine. 
     
     
         73 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 24 hours the sepsis patient will have a urine output of less than 0.5 ml/kg/hr over a 6 hour period. 
     
     
         74 . A method according to  claim 63 , wherein said correlating step comprises assigning a likelihood that within 24 hours the sepsis patient will experience an increase of 0.3 mg/dL or greater in serum creatinine. 
     
     
         75 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has not experienced a 2-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         76 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has a urine output of at least 0.5 ml/kg/hr over the 12 hours preceding the time at which the body fluid sample is obtained. 
     
     
         77 . A method according to one of  claims 1 - 5 , wherein the sepsis patient (i) has not experienced a 2-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained, (ii) has a urine output of at least 0.5 ml/kg/hr over the 2 hours preceding the time at which the body fluid sample is obtained, and (iii) has not experienced an increase of 0.3 mg/dL or greater in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         78 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has not experienced a 3-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         79 . A method according to one of  claims 1 - 5 , wherein the sepsis patient has a urine output of at least 0.3 ml/kg/hr over the 24 hours preceding the time at which the body fluid sample is obtained, or anuria over the 12 hours preceding the time at which the body fluid sample is obtained. 
     
     
         80 . A method according to one of  claims 1 - 5 , wherein the sepsis patient (i) has not experienced a 3-fold or greater increase in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained, (ii) has a urine output of at least 0.3 ml/kg/hr over the 24 hours preceding the time at which the body fluid sample is obtained, or anuria over the 12 hours preceding the time at which the body fluid sample is obtained, and (iii) has not experienced an increase of 0.3 mg/dL or greater in serum creatinine over a baseline value determined prior to the time at which the body fluid sample is obtained. 
     
     
         81 . A method according to one of  claims 1 - 5 , wherein said correlating step comprises assigning one or more of: a likelihood that within 72 hours the sepsis patient will (i) experience a 2-fold or greater increase in serum creatinine (ii) have a urine output of less than 0.5 ml/kg/hr over a 12 hour period, or (iii) experience an increase of 0.3 mg/dL or greater in serum creatinine. 
     
     
         82 . A method according to  claim 81 , wherein said correlating step comprises assigning one or more of: a likelihood that within 48 hours the sepsis patient will (i) experience a 2-fold or greater increase in serum creatinine (ii) have a urine output of less than 0.5 ml/kg/hr over a 6 hour period, or (iii) experience an increase of 0.3 mg/dL or greater in serum creatinine. 
     
     
         83 . A method according to  claim 81 , wherein said correlating step comprises assigning one or more of: a likelihood that within 24 hours the sepsis patient will (i) experience a 2-fold or greater increase in serum creatinine, or (ii) have a urine output of less than 0.5 ml/kg/hr over a 6 hour period. 
     
     
         84 . A method according to  claim 81 , wherein said correlating step comprises assigning a likelihood that within 72 hours the sepsis patient will experience a 2-fold or greater increase in serum creatinine. 
     
     
         85 . A method according to  claim 81 , wherein said correlating step comprises assigning a likelihood that within 72 hours the sepsis patient will have a urine output of less than 0.5 ml/kg/hr over a 6 hour period. 
     
     
         86 . A method according to  claim 81 , wherein said correlating step comprises assigning a likelihood that within 48 hours the sepsis patient will experience a 2-fold or greater increase in serum creatinine. 
     
     
         87 . A method according to  claim 81 , wherein said correlating step comprises assigning a likelihood that within 48 hours the sepsis patient will have a urine output of less than 0.5 ml/kg/hr over a 6 hour period. 
     
     
         88 . A method according to  claim 81 , wherein said correlating step comprises assigning a likelihood that within 24 hours the sepsis patient will experience a 2-fold or greater increase in serum creatinine. 
     
     
         89 . A method according to  claim 81 , wherein said correlating step comprises assigning a likelihood that within 24 hours the sepsis patient will have a urine output of less than 0.5 ml/kg/hr over a 6 hour period. 
     
     
         90 . A method according to one of  claims 1 - 5 , wherein said correlating step comprises assigning one or more of: a likelihood that within 72 hours the sepsis patient will (i) experience a 3-fold or greater increase in serum creatinine, or (ii) have a urine output of less than 0.3 ml/kg/hr over a 24 hour period or anuria over a 12 hour period. 
     
     
         91 . A method according to  claim 90 , wherein said correlating step comprises assigning one or more of: a likelihood that within 48 hours the sepsis patient will (i) experience a 3-fold or greater increase in serum creatinine, or (ii) have a urine output of less than 0.3 ml/kg/hr over a 24 hour period or anuria over a 12 hour period. 
     
     
         92 . A method according to  claim 90 , wherein said correlating step comprises assigning one or more of: a likelihood that within 24 hours the sepsis patient will (i) experience a 3-fold or greater increase in serum creatinine, or (ii) have a urine output of less than 0.3 ml/kg/hr over a 24 hour period or anuria over a 12 hour period. 
     
     
         93 . A method according to  claim 90 , wherein said correlating step comprises assigning a likelihood that within 72 hours the sepsis patient will experience a 3-fold or greater increase in serum creatinine. 
     
     
         94 . A method according to  claim 90 , wherein said correlating step comprises assigning a likelihood that within 72 hours the sepsis patient will have a urine output of less than 0.3 ml/kg/hr over a 24 hour period or anuria over a 12 hour period. 
     
     
         95 . A method according to  claim 90 , wherein said correlating step comprises assigning a likelihood that within 48 hours the sepsis patient will experience a 3-fold or greater increase in serum creatinine. 
     
     
         96 . A method according to  claim 90 , wherein said correlating step comprises assigning a likelihood that within 48 hours the sepsis patient will have a urine output of less than 0.3 ml/kg/hr over a 24 hour period or anuria over a 12 hour period. 
     
     
         97 . A method according to  claim 90 , wherein said correlating step comprises assigning a likelihood that within 24 hours the sepsis patient will experience a 3-fold or greater increase in serum creatinine. 
     
     
         98 . A method according to  claim 90 , wherein said correlating step comprises assigning a likelihood that within 24 hours the sepsis patient will have a urine output of less than 0.3 ml/kg/hr over a 24 hour period or anuria over a 12 hour period. 
     
     
         99 . A method according to one of  claims 1 - 98 , wherein the body fluid sample is a urine sample. 
     
     
         100 . A method according to one of  claims 1 - 99 , wherein said method comprises performing assays that detect one, two or three, or more of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase. 
     
     
         101 . Measurement of one or more biomarkers selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase for the evaluation of renal injury. 
     
     
         102 . Measurement of one or more biomarkers selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass 11, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase for the evaluation of acute renal injury. 
     
     
         103 . A kit, comprising:
 reagents for performing one or more assays configured to detect one or more kidney injury markers selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase.   
     
     
         104 . A kit according to  claim 103 , wherein said reagents comprise one or more binding reagents, each of which specifically binds one of said of kidney injury markers. 
     
     
         105 . A kit according to  claim 104 , wherein a plurality of binding reagents are contained in a single assay device. 
     
     
         106 . A kit according to  claim 103 , wherein at least one of said assays is configured as a sandwich binding assay. 
     
     
         107 . A kit according to  claim 103 , wherein at least one of said assays is configured as a competitive binding assay. 
     
     
         108 . A kit according to one of  claims 103 - 107 , wherein said one or more assays comprise assays that detect one, two or three, or more of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase. 
     
     
         109 . A method for evaluating biomarker levels in a body fluid sample, comprising:
 obtaining a body fluid sample from a subject selected for evaluation based on a determination that the subject has sepsis; and   performing a plurality of analyte binding assays configured to detect a plurality of biomarkers, one or more of which is selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase by introducing the urine sample obtained from the subject into an assay instrument which (i) contacts a plurality of reagents which specifically bind for detection the plurality of biomarkers with the urine sample, and (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to a respective specific binding reagent in the plurality of reagents, and (iii) correlates the one or more assay results to a likelihood of worsening or improving renal function.   
     
     
         110 . A method according to  claim 109 , wherein the body fluid sample is a urine sample. 
     
     
         111 . A method according to  claim 109  or  110 , wherein the correlation is to a likelihood of future acute renal injury (AKI) or acute renal failure (ARF). 
     
     
         112 . A method according to  claim 111 , wherein the correlation is to a likelihood of of a future acute renal injury 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, 18 hours, and 12 hours. 
     
     
         113 . A method according to  claim 111 , wherein the wherein the correlation is to a likelihood of of a future acute renal failure 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, 18 hours, and 12 hours. 
     
     
         114 . A method according to one of  claims 109 - 113 , wherein the plurality of assays are immunoassays performed by (i) introducing the urine sample into an assay device comprising a plurality of antibodies, at least one of which binds to each biomarker which is assayed, and (ii) generating an assay result indicative of binding of each biomarker to its respective antibody. 
     
     
         115 . A method according to one of  claims 109 - 110 , wherein the subject is in RIFLE stage 0 or R. 
     
     
         116 . A method according to one of  claims 109 - 110 , wherein the subject is in RIFLE stage 0, R, or I. 
     
     
         117 . A system for evaluating biomarker levels, comprising:
 a plurality of reagents which specifically bind for detection the plurality of biomarkers, one or more of which is selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C—X—C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C—C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C—X—C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C—C motif chemokine 18, Matrilysin, C—X—C motif chemokine 11, and Antileukoproteinase;   an assay instrument configured to receive a urine sample and contact the plurality of reagents with the urine sample to generate one or more assay results indicative of binding of each biomarker which is assayed to a respective specific binding reagent in the plurality of reagents, and to correlate the one or more assay results to a likelihood of worsening or improving renal function   
     
     
         118 . A system according to  claim 117 , wherein the reagents comprise a plurality of antibodies, at least one of which binds to each of the biomarkers which are assayed. 
     
     
         119 . A system according to  claim 118 , wherein assay instrument comprises an assay device and an assay device reader, wherein the plurality of antibodies are immobilized at a plurality of predetermined locations within the assay device, wherein the assay device is configured to receive the urine sample such that the urine sample contacts the plurality of predetermined locations, and wherein the assay device reader interrogates the plurality of predetermined locations to generate the assay results.