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 Follistatin-related protein 3, Basigin, Cathepsin B, and Tenascin as diagnostic and prognostic biomarker assays in renal injuries.

1 - 111 . (canceled) 
     
     
         112 . A method of treating a subject, the method comprising:
 (a) performing an assay method to detect a level of Follistatin-related protein 3 in a body fluid sample obtained from a subject, wherein the Follistatin-related protein 3 comprises amino acid residues 27-263 of SEQ ID NO: 1, and wherein the sample has an elevated level of the Follistatin-related protein 3 as compared to a predetermined threshold value;   (b) determining that the subject is at an increased risk of a persistent RIFLE I (Injury) acute kidney injury or a persistent RIFLE F (Failure) acute kidney injury based on the level of the Follistatin-related protein 3 in the sample; and   (c) treating the subject determined to be at an increased risk as in step (b) by 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 Follistatin-related protein 3 consists of amino acid residues 27-263 of SEQ ID NO: 1. 
     
     
         114 . The method of  claim 112 , wherein the determining comprises determining that the subject has an increased likelihood of the persistent RIFLE I acute kidney injury or the persistent RIFLE F acute kidney injury that persists for a period of 24 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 persistent RIFLE I acute kidney injury or the persistent RIFLE F acute kidney injury that persists for a period of 48 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 persistent RIFLE I acute kidney injury or the persistent RIFLE F acute kidney injury that persists for a period of 72 hours or more after the time the sample is obtained from the subject. 
     
     
         117 . The method of  claim 112 , wherein the determining comprises determining that the subject has an increased likelihood of a future persistence of a RIFLE I acute kidney injury or a future persistence of a RIFLE F acute kidney injury that starts after the time the sample is obtained. 
     
     
         118 . The method of  claim 117 , wherein the future persistence comprises a persistence period that starts within 24 hours after the sample is obtained. 
     
     
         119 . The method of  claim 117 , wherein the future persistence comprises a persistence period that starts within 48 hours after the sample is obtained. 
     
     
         120 . The method of  claim 117 , wherein the future persistence comprises a persistence period that starts within 72 hours after the sample is obtained. 
     
     
         121 . The method of  claim 112 , wherein the persistent RIFLE I acute kidney injury or the persistent RIFLE F acute kidney injury comprises a persistence period that starts at the time the sample is obtained. 
     
     
         122 . The method of  claim 121 , wherein the determining comprises determining that the subject has an increased likelihood of the persistent RIFLE I acute kidney injury or the persistent RIFLE F acute kidney injury that persists for a period of 24, 48, or 72 hours after the time the sample is obtained from the subject. 
     
     
         123 . The method of  claim 112 , wherein the determining comprises determining that the subject is at an increased risk of a persistent RIFLE F acute kidney injury within 48 hours after the sample is obtained, wherein the duration of the persistent RIFLE F acute kidney injury comprises a 72-hour period with a minimum RIFLE stage of RIFLE F. 
     
     
         124 . The method of  claim 123 , wherein the duration of the persistent RIFLE F acute kidney injury comprises a 7-day period with a minimum RIFLE stage of RIFLE F. 
     
     
         125 . The method of  claim 112 , wherein the method further comprises
 contacting the sample with a binding reagent which binds to the Follistatin-related protein 3, and   generating an assay result indicative of binding of the Follistatin-related protein 3 to the binding reagent.   
     
     
         126 . The method of  claim 125 , wherein the binding reagent is an antibody. 
     
     
         127 . The method of  claim 112 , further comprising performing an assay method to detect a level of one or more of Basigin, Cathepsin B, and Tenascin in the sample, wherein
 the Basigin comprises amino acid residues 22-385 of SEQ ID NO: 4, amino acid residues 22-23 and 140-385 of SEQ ID NO: 4, amino acid residues 210-385 of SEQ ID NO: 4, and/or amino acid residues 192-385 of SEQ ID NO: 4,   the Cathepsin B comprises amino acid residues 18-79 of SEQ ID NO: 2, amino acid residues 80-333 of SEQ ID NO: 2, amino acid residues 80-126 of SEQ ID NO: 2, amino acid residues 129-133 of SEQ ID NO: 2, and/or amino acid residues 334-339 of SEQ ID NO: 2,   the Tenascin comprises amino acid residues 23-2201 of SEQ ID NO: 3, amino acid residues 23-1071, 1436-1526, and 1618-2201 of SEQ ID NO: 3, amino acid residues 23-1071 and 1436-2201 of SEQ ID NO: 3, amino acid residues 23-1526 and 1618-2201 of SEQ ID NO: 3, amino acid residues 23-1071 and 1618-2201 of SEQ ID NO: 3, and/or amino acid residues 23-1071 and 1709-2201 of SEQ ID NO: 3, and   wherein the subject has an elevated level of the one or more of Basigin, Cathepsin B, and Tenascin as compared to a predetermined threshold value.   
     
     
         128 . The method of  claim 127 , wherein the method further comprises
 contacting the sample with a binding reagent which binds to the Follistatin-related protein 3 and generating an assay result indicative of binding of the Follistatin-related protein 3 to the binding reagent, and   contacting the sample with a binding reagent which binds to the one or more of Basigin, Cathepsin B, and Tenascin, and generating an assay result indicative of binding of the one or more of Basigin, the Cathepsin B, and the Tenascin to the binding reagent.   
     
     
         129 . The method of  claim 128 , wherein the binding agent is an antibody. 
     
     
         130 . The method of  claim 112 , wherein the body fluid sample is a urine sample, a blood sample, a plasma sample, or a serum sample. 
     
     
         131 . A method of treating a subject, the method comprising:
 (a) performing an assay method to detect a level of Follistatin-related protein 3 in a body fluid sample obtained from a subject, wherein the Follistatin-related protein 3 comprises amino acid residues 27-263 of SEQ ID NO: 1, and wherein the sample has an elevated level of the Follistatin-related protein 3 as compared to a predetermined threshold value;   (b) determining that the subject is at an increased risk of a persistent RIFLE F (Failure) acute kidney injury within 48 hours of the time the sample is obtained, based on the level of the Follistatin-related protein 3 in the sample, wherein the duration of the persistent RIFLE F acute kidney injury comprises a 72-hour period with a minimum RIFLE stage of RIFLE F; and   (c) treating the subject determined to be at an increased risk as in step (b) by 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.