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 assays that detect one or more of Insulin-like growth factor-binding protein 2, Insulin-like growth factor-binding protein 3, Insulin-like growth factor-binding protein 4, and Insulin like growth factor-binding protein 6 as diagnostic and prognostic biomarker assays in renal injuries.

1 - 111 . (canceled) 
     
     
         112 . A method of treating acute kidney injury comprising:
 (a) detecting a level of one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6 in a body fluid sample obtained from a subject;   (b) determining that the subject is at increased risk of persistence of a RIFLE I acute kidney injury or persistence of a RIFLE F acute kidney injury based on the level of one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6 in the body fluid sample; and   (c) administering to the subject at the increased risk of persistence of a RIFLE I acute kidney injury or persistence of a RIFLE F acute kidney injury a treatment regimen comprising one or more of 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, modifying diuretic administration, monitoring and optimizing hemodynamics and fluid administration, and adjusting dosing of renally excreted substances.   
     
     
         113 . The method of  claim 112 , wherein the determining comprises determining that the subject has an increased likelihood of the persistence of a RIFLE I acute kidney injury or the persistence of a RIFLE F acute kidney injury for a period of 24 hours or more after the time the sample is obtained from the subject. 
     
     
         114 . The method of  claim 112 , wherein the determining comprises determining that the subject has an increased likelihood of the persistence of a RIFLE I acute kidney injury or the persistence of a RIFLE F acute kidney injury for a period of 48 hours or more after the time the sample is obtained from the subject. 
     
     
         115 . The method of  claim 112 , wherein the determining comprises determining that the subject has an increased likelihood of the persistence of a RIFLE I acute kidney injury or the persistence of a RIFLE F acute kidney injury for a period of 72 hours or more after the time the sample is obtained from the subject. 
     
     
         116 . The method of  claim 112 , wherein the determining comprises determining that the subject has an increased likelihood of the persistence of a RIFLE I acute kidney injury or the persistence of a RIFLE F acute kidney injury for a period of 24, 48, or 72 hours after the time the sample is obtained from the subject. 
     
     
         117 . The method of  claim 112 , wherein the persistence of a RIFLE I acute kidney injury or the persistence of a RIFLE F acute kidney injury is future persistence of a RIFLE I acute kidney injury or future persistence of a RIFLE F acute kidney injury. 
     
     
         118 . The method of  claim 112 , wherein the persistence of a RIFLE I acute kidney injury or the persistence of a RIFLE F acute kidney injury is future persistence of a RIFLE F acute kidney injury. 
     
     
         119 . The method of  claim 112 , wherein the persistence of a RIFLE I acute kidney injury or the persistence of a RIFLE F acute kidney injury is future persistence of a RIFLE I acute kidney injury. 
     
     
         120 . The method of  claim 117 , wherein the future persistence comprises a persistence period that starts within 24 hours after the sample is obtained. 
     
     
         121 . The method of  claim 117 , wherein the future persistence comprises a persistence period that starts within 48 hours after the sample is obtained. 
     
     
         122 . The method of  claim 117 , wherein the future persistence comprises a persistence period that starts within 72 hours after the sample is obtained. 
     
     
         123 . The method of  claim 112 , wherein the persistence comprises a persistence period that starts at the time the sample is obtained. 
     
     
         124 . The method of  claim 112 , wherein the detecting comprises detecting an elevated level of the one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6 in the sample as compared to a predetermined threshold level. 
     
     
         125 . The method of  claim 112 , wherein the detecting comprises:
 contacting all or a portion of the sample with a binding reagent which binds to the one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6; and   generating an assay result indicative of binding of the one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6.   
     
     
         126 . The method of  claim 125 , wherein the assay result is a measured concentration of the one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6. 
     
     
         127 . The method of  claim 125 , wherein the assay result is a composite of a plurality of assay results. 
     
     
         128 . The method of  claim 125 , wherein the binding reagent is an antibody. 
     
     
         129 . The method of  claim 112 , wherein the body fluid sample is a urine sample. 
     
     
         130 . A method of treating acute kidney injury comprising:
 (a) detecting a level of one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6 in a urine sample obtained from a subject;   (b) determining that the subject is at increased risk of persistence of a RIFLE F acute kidney injury based on the level of one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6 in the sample,   wherein the persistence comprises a persistence period that starts at or after the time the sample is obtained and at or before 48 hours after the sample is obtained, and lasts for a period of 72 hours or more; and   (c) administering to the subject at the increased risk of persistence of a RIFLE F acute kidney injury a treatment regimen comprising one or more of 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, modifying diuretic administration, monitoring and optimizing hemodynamics and fluid administration, and adjusting dosing of renally excreted substances.   
     
     
         131 . A method of treating acute kidney injury comprising:
 (a) detecting a level of one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6 in a urine sample obtained from a subject;   (b) determining that the subject is at increased risk of persistence of a RIFLE I acute kidney injury based on the level of one or more of insulin-like growth factor-binding protein 2, insulin-like growth factor-binding protein 3, insulin-like growth factor-binding protein 4, and insulin-like growth factor-binding protein 6 in the sample,   wherein the persistence comprises a persistence period that starts at or after the time the sample is obtained and at or before 48 hours after the sample is obtained, and lasts for a period of 72 hours or more; and   (c) administering to the subject at the increased risk of persistence of a RIFLE I acute kidney injury a treatment regimen comprising one or more of 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, modifying diuretic administration, monitoring and optimizing hemodynamics and fluid administration, and adjusting dosing of renally excreted substances.