Method for the early identification and prediction of kidney injury

Abstract

A method for the early identification and prediction of elevated blood creatinine levels resulting from a reduction in kidney function in a subject, comprises contacting a urine sample from the subject with a capture molecule for a biomarker specific for the distal region of the renal tubule and which biomarker is released from said region when there is damage to said region indicative and predictive of elevated blood creatinine levels resulting from a reduction in kidney function. The method can be used to detect Acute Kidney Injury (AKI) caused by many conditions or diseases or through the administration of drugs. The method can indicate and/or predict a reduction in kidney function significantly earlier than the current standard creatinine test. Methods for predicting a need for renal replacement therapy (RRT) are also disclosed.

1 . A method for the early identification and prediction of elevated blood creatinine levels resulting from a reduction in kidney function in a subject, which method comprises contacting a urine sample from the subject with a capture molecule for a biomarker specific for the distal region of the renal tubule and which biomarker is released from said region when there is damage to said region indicative and predictive of elevated blood creatinine levels resulting from a reduction in kidney function. 
   
   
       2 . A method according to  claim 1 , wherein the reduction in kidney function is caused by Acute Kidney Injury (AKI). 
   
   
       3 . A method according to  claim 2 , wherein the AKI is caused by a condition or disease selected from age, burns, pre-existing chronic kidney disease, reduced effective arterial volume, volume depletion, nephrotic syndrome, congestive heart failure, cirrhosis, sepsis, type I diabetes, type II diabetes, obesity, inflammation, surgery, solid organ transplant, allogenic bone marrow transplant, mechanical ventilation and/or trauma. 
   
   
       4 . A method according to  claim 2 , wherein the AKI is caused by administration of a drug to the subject. 
   
   
       5 . A method according to  claim 4 , wherein the drug is selected from aminoglycosides, non-steroidal anti-inflammatory drugs and radiocontrast drugs. 
   
   
       6 . A method according to  claim 2 , wherein the AKI is caused by renal ischemia in a patient undergoing cardiothoracic (CT) surgery. 
   
   
       7 . A method according to  claim 6 , wherein the biomarker is detectable as early as intraoperatively, allowing for immediate corrective medical intervention. 
   
   
       8 . A method according to  claim 6 , wherein the biomarker is detectable in the recovery stage post CT surgery, allowing for immediate corrective medical intervention. 
   
   
       9 . A method according to  claim 8 , wherein the biomarker is detectable prior to transfer of the patient to the Intensive Care Unit (ICU). 
   
   
       10 . A method according to  claim 1 , wherein the biomarker is pi glutathione S transferase (πGST). 
   
   
       11 . A method according to  claim 1 , wherein the biomarker is detected by immunoassay. 
   
   
       12 . A method according to  claim 11 , wherein the capture molecule is an antibody to πGST. 
   
   
       13 . A method according to  claim 10 , wherein the biomarker is detected enzymatically. 
   
   
       14 . A method according to  claim 1 , wherein the biomarker is detected by a point-of-care assay. 
   
   
       15 . πGST for use as a biomarker for the early identification and prediction of elevated blood creatinine levels resulting from a reduction in kidney function. 
   
   
       16 . A method for predicting a need for renal replacement therapy (RRT) in a patient comprising:
 determining a concentration of glutathione S transferase (GST) in a first urine sample from the patient; and   wherein a need for RRT is predicted when the GST concentration is determined to be elevated in comparison to a patient without kidney injury.   
   
   
       17 . A method according to  claim 16 , further comprising contacting a urine sample from the patient with a capture molecule for a GST isozyme. 
   
   
       18 . A method according to  claim 16 , wherein the GST is πGST. 
   
   
       19 . A method according to  claim 16 , wherein the GST is detected by immunoassay. 
   
   
       20 . A method according to  claim 19 , wherein the capture molecule is an antibody to πGST. 
   
   
       21 . A method according to  claim 16 , wherein the GST is detected enzymatically. 
   
   
       22 . A method according to  claim 16 , wherein the GST is detected by a point-of-care assay. 
   
   
       23 . A method for predicting a need for RRT in a patient comprising:
 determining a concentration of GST in two urine samples taken at least 24 hours apart from the patient; and   wherein a need for RRT is predicted when the GST concentration is determined to be elevated in the two urine samples.   
   
   
       24 . A method according to  claim 16 , wherein the elevated GST concentration in urine is ≧30 ng/ml. 
   
   
       25 . A method according to  claim 16 , wherein the elevated GST concentration in urine is ≧60 ng/ml. 
   
   
       26 . A method according to  claim 16 , wherein the elevated GST concentration in urine is ≧70 ng/ml. 
   
   
       27 . A method according to  claim 16 , wherein the elevated GST concentration in urine is ≧80 ng/ml. 
   
   
       28 . A method according to  claim 16 , wherein the elevated GST concentration in urine is ≧90 ng/ml or more. 
   
   
       29 . A method according to  claim 16 , wherein the GST is a πGST isozyme. 
   
   
       30 . A method according to  claim 16 , wherein the patient is affected by an age-related condition, burns, pre-existing chronic kidney disease, reduced effective arterial volume, volume depletion, nephrotic syndrome, congestive heart failure, cirrhosis, sepsis, type I diabetes, type II diabetes, obesity, inflammation, surgery, being a solid organ transplant recipient, being an allogenic bone marrow transplant recipient, mechanical ventilation and/or trauma or has taken or has been administered an antibiotic, drug and/or toxin. 
   
   
       31 . A method according to  claim 16 , further comprising detecting for the presence of risk factors for RRT in the patient wherein the risk factor is selected from the group consisting of elevated serum creatinine concentration, type I diabetes, type II diabetes, hypertension, dyslipidemia, hyperglycaemia, proteinuria and hypoalbuminemia.