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 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 Tumor necrosis factor receptor superfamily member 8, Alpha-Fetoprotein, Thyroxine-binding globulin, Prostate-specific antigen (free form), Apolipoprotein A, Apolipoprotein E, Thyrotropin subunit beta, Platelet-derived growth factor B/B dimer, C—C motif chemokine 7, C—C motif chemokine 26, Complement C4-B, Corticotropin, Interferon alpha-2, Interleukin-4 receptor alpha chain, Insulin-like growth factor-binding protein 4, Insulin-like growth factor-binding protein 5, Interleukin 21, Interleukin 23 alpha subunit, Interleukin-28A, Interleukin-33, Lutropin subunit beta, Matrix Metalloproteinase-1, Neural cell adhesion molecule 1, Pigment epithelium-derived factor, Vascular endothelial growth factor receptor 2, Vascular endothelial growth factor receptor 3, and IgG4 as diagnostic and prognostic biomarkers in renal injuries.

We claim: 
     
         1 . A method for evaluating renal status in a subject, comprising:
 performing an assay configured to detect Insulin-like growth factor-binding protein 4 by introducing a body fluid sample obtained from the subject into an assay instrument which (i) contacts all or a portion of the body fluid sample with a binding reagent which specifically binds for detection Insulin-like growth factor-binding protein 4, and (ii) generates one or more assay results indicative of binding of Insulin-like growth factor-binding protein 4 to its binding reagent;   correlating the assay result(s) to the renal status of the subject by using the assay result(s) to assign the patient to a predetermined subpopulation of individuals having a known predisposition of a current or future acute renal injury, wherein said future acute injury is within 72 hours of the time at which the body fluid is obtained, the assignment made by comparing the assay result(s) or a value derived therefrom to a threshold value obtained from a population study, wherein the threshold separates the population into a first subpopulation and a second subpopulation, the first subpopulation being at an increased predisposition for future acute renal injury meeting the definition of RIFLE I or F within 72 hours of the time the body fluid sample is obtained relative to the second subpopulation; and   treating the patient based on the predetermined subpopulation of individuals to which the patient is assigned, wherein when the assay result or value derived therefrom assigns the subject to the first subpopulation, the subject is treated by 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.   
     
     
         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 1 , wherein the assay result is a measured concentration of Insulin-like growth factor-binding protein 4. 
     
     
         5 . A method according to  claim 1 , wherein a plurality of assay results, one of which is the assay result indicative of binding of Insulin-like growth factor-binding protein 4 to its binding reagent, are combined using a function that converts the plurality of assay results into a single composite result. 
     
     
         6 . 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. 
     
     
         7 . 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. 
     
     
         8 . A method according to  claim 1 , 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. 
     
     
         9 . 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. 
     
     
         10 . 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). 
     
     
         11 . 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. 
     
     
         12 . 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. 
     
     
         13 . 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. 
     
     
         14 . 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. 
     
     
         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 renal replacement therapy 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 a need for renal transplantation in said subject. 
     
     
         17 . A method according to  claim 1 , wherein the subject is in RIFLE stage 0 or R. 
     
     
         18 . A method according to  claim 1 , wherein the subject is not in acute renal failure.