Urine Biomarkers for Prediction of Recovery After Acute Kidney Injury: Proteomics

Abstract

This invention is related to the field of the prevention and treatment of kidney disease. The treatment of kidney disease may be tailored depending upon the need for, or expectation of, renal recovery. For example, renal recovery can be determined by monitoring urine biomarkers related to the development of chronic kidney disease. For example, a normalized time course of approximately fourteen Days measuring urinary proteins can be used to establish the risk of recovery versus non-recovery in patient's having suffered an acute kidney injury. Alternatively, the invention describes signature protein expression profiles to establish the probability of renal recovery and/or renal non-recovery.

1 . A composition comprising an renal injury biomarker, wherein said biomarker comprises at least a fragment of at least one protein selected from the group consisting of ferritin, beta globin, catalase, alpha globin, epidermal growth factor receptor pathway substrate 8, mucin isoform precursor, ezrin, delta globin, moesin, phosphoprotein isoform, annexin A2, myoglobin, hemopexin, serine proteinase inhibitor, serpine peptidase inhibitor, CD14 antigen precursor, fibronectin isoform preprotein, angiotensinogen preprotein, complement component precursor, carbonic anhydrase, uromodulin precursor, complement factor H, complement component 4 BP, heparan sulfate proteoglycan 2, olfactomedian-4, leucine rich alpha-2 glycoprotein, ring finger protein 167, inter-alpha globulin inhibitor H4, heparan sulfate proteoglycan 2, N-acylshingosine aminohydrolase, serine proteinase inhibitor clade A member 1, mucin 1, clusterin isoform 1, brain abundant membrane attached signal protein 1, dipeptidase 1, fibronectin 1 isoform 5 preprotein, angiotensinogen preproprotein, carbonic anhydrase, and uromodulin precursor. 
     
     
         2 . The composition of  claim 1 , wherein said composition further comprises a biological fluid sample. 
     
     
         3 . The composition of  claim 2 , wherein said biological fluid sample is collected from a patient between 1 day and 14 days after a kidney injury. 
     
     
         4 . The composition of  claim 2 , wherein said biological fluid sample is a human urine sample. 
     
     
         5 . The composition of  claim 1 , wherein said renal injury biomarker in said biological fluid sample is at at least one level selected from the group consisting of at least 2.5 fold higher, at least 2.0 fold higher, at least 1.5 fold higher, at least 1.25 fold higher as compared to an expected level in a renal recovery group. 
     
     
         6 . The composition of  claim 1 , wherein said renal injury biomarker in said biological fluid sample is at at least one level selected from the group consisting of at least 2.5 fold lower, at least 2.0 fold lower, at least 1.5 fold lower and at least 1.25 fold lower as compared to an expected level in a renal recovery group. 
     
     
         7 - 10 . (canceled) 
     
     
         11 . A kit, comprising:
 a) a first container comprising an antibody is specifically directed to at least one of a plurality of renal injury biomarkers, wherein said biomarkers comprise at least a fragment of a protein selected from the group consisting of ferritin, beta globin, catalase, alpha globin, epidermal growth factor receptor pathway substrate 8, mucin isoform precursor, ezrin, delta globin, moesin, phosphoprotein isoform, annexin A2, myoglobin, hemopexin, serine proteinase inhibitor, serpine peptidase inhibitor, CD14 antigen precursor, fibronectin isoform preprotein, angiotensinogen preprotein, complement component precursor, carbonic anhydrase, uromodulin precursor, complement factor H, complement component 4 BP, heparan sulfate proteoglycan 2, olfactomedian-4, leucine rich alpha-2 glycoprotein, ring finger protein 167, inter-alpha globulin inhibitor H4, heparan sulfate proteoglycan 2, N-acylshingosine aminohydrolase, serine proteinase inhibitor clade A member 1, mucin 1, clusterin isoform 1, brain abundant membrane attached signal protein 1, dipeptidase 1, fibronectin 1 isoform 5 preprotein, angiotensinogen preproprotein, carbonic anhydrase, and uromodulin precursor;   b) instructions for determining whether said biomarker is overexpressed as compared to a renal recovery group comprising individuals without an acute renal injury;   c) instructions for determining whether said biomarker is underexpressed as compared to said renal recovery group; and   d) instructions for determining a probability value of renal non-recovery for a patient from an acute renal injury by a combination of receiver operated characteristic area under the curve determinations for overexpression or underexpression of said biomarker as compared to a plurality of diagnostic threshold values.   
     
     
         12 . The kit of  claim 11 , wherein said antibody is a monoclonal antibody. 
     
     
         13 . The kit of  claim 12 , wherein said monoclonal antibody is specifically directed to said biomarker protein fragment. 
     
     
         14 . The kit of  claim 11 , further comprising instructions for treating said patient during the development of said renal disease with a treatment regimen selected from the group consisting of: i) said treatment regimen comprising adverse effects when said probability value of non-recovery from said acute injury is greater than 50%, and ii) said treatment regimen without adverse effects when said probability value of non-recovery from said acute renal injury is less than 50%. 
     
     
         15 . The kit of  claim 14 , wherein said instructions identify that said treatment regimen as selected from the group consisting of initiating renal replacement therapy, withdrawing kidney damaging compounds, kidney transplantation, delaying or avoiding kidney damaging procedures and modifying diuretic administration. 
     
     
         16 . The kit of  claim 11 , wherein said interactions identify that said overexpressed biomarker is between approximately 1.5 fold-1.5 fold higher in comparison to said renal recovery group. 
     
     
         17 . The kit of  claim 11 , wherein said instructions identify that said underexpressed biomarker is between approximately 1.5 fold-2.0 fold lower in comparison to said renal recovery group. 
     
     
         18 . The kit of  claim 11 , wherein said instructions identify that said probability value of non-recovery from said acute renal injury is less than 10%. 
     
     
         19 . The kit of  claim 11 , wherein said instructions identify that said probability value of non-recovery from said acute renal injury is greater than 75%. 
     
     
         20 . The kit of  claim 11 , wherein said instructions identify that said probability value of non-recovery from said acute renal injury is greater than 90%.