GDF-15 and/or Troponin T for Predicting Kidney Failure in Heart Surgery Patients

Abstract

The present disclosure relates to the field of laboratory diagnostics. Specifically, means and methods are disclosed for determining a patient's risk of suffering from acute kidney injury after a surgical procedure based on the detection of GDF-15, troponin T and/or a natriuretic peptide.

1 . A method for predicting a risk of acute kidney injury (AKI) in a patient subjected to a surgical procedure, comprising:
 a) contacting, in vitro, a sample obtained from the patient before the patient undergoes the surgical procedure with a ligand comprising specific binding affinity for GDF-15;   b) determining the amount of GDF-15 in the sample; and   c) providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1078 pg/ml, or that the patient has an increased risk of AKI if the amount of GDF-15 is above about 1717 pg/ml.   
     
     
         2 . The method of  claim 1 , wherein the surgical procedure is orthopedic surgery, a tumor resection, surgery of the gastrointestinal tract not involving tumor resection, or cardiac surgery. 
     
     
         3 . The method of  claim 1 , wherein the ligand comprising specific binding affinity for GDF-15 is an antibody, nucleic acid, receptor, binding partner, or aptamer. 
     
     
         4 . The method of  claim 1 , wherein the amount of GDF-15 in the sample is determined by measuring a signal obtained from GDF-15, wherein the intensity of the signal directly correlates with the number of molecules of GDF-15 in the sample. 
     
     
         5 . The method of  claim 1 , wherein the amount of GDF-15 in the sample is determined by measuring a signal obtained from a secondary component, wherein the intensity of the signal indirectly correlates with the number of molecules of GDF-15 in the sample. 
     
     
         6 . The method of  claim 1 , wherein the patient is predicted to have an increased risk of AKI requiring hemodialysis if the amount of GDF-15 is above about 2573 pg/ml. 
     
     
         7 . The method of  claim 1 , further comprising contacting, in vitro, the sample obtained from the patient before the patient undergoes the surgical procedure with a second ligand comprising specific binding affinity for troponin T; determining the amount of troponin T in the sample; and providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1078 pg/ml and the amount of troponin T is below about 13.3 pg/ml, or that the patient has an increased risk of AKI if the amount of GDF-15 is above about 1717 pg/ml and the amount of troponin T is above about 25.5 pg/ml. 
     
     
         8 . The method of  claim 1 , further comprising contacting, in vitro, the sample obtained from the patient before the patient undergoes the surgical procedure with a second ligand comprising specific binding affinity for NT-proBNP; determining the amount of NT-proBNP in the sample; and providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1078 pg/ml and the amount of NT-proBNP is below about 488.2 pg/ml, or that the patient has an increased risk of AKI if the amount of GDF-15 is above about 1717 pg/ml and the amount of NT-proBNP is above about 1118.7 pg/ml. 
     
     
         9 . The method of  claim 1 , further comprising contacting, in vitro, the sample obtained from the patient before the patient undergoes the surgical procedure with a second ligand comprising specific binding affinity for troponin T and a third ligand comprising specific binding affinity for NT-proBNP; determining the amounts of troponin T and NT-proBNP in the sample; and providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1078 pg/ml, the amount of troponin T is below about 13.3 pg/ml, and the amount of NT-proBNP is below about 488.2 pg/ml; or that the patient has an increased risk of AKI if the amount of GDF-15 is above about 1717 pg/ml, the amount of troponin T is above about 25.5 pg/ml, and the amount of NT-proBNP is above about 1118.7 pg/ml. 
     
     
         10 . A method for predicting a risk of acute kidney injury (AKI) in a patient subjected to a surgical procedure, comprising:
 a) contacting, in vitro, a sample obtained from the patient after the patient undergoes the surgical procedure with an antibody immunoreactive for GDF-15;   b) determining the amount of GDF-15 in the sample; and   c) providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1807 pg/ml and that the patient has an increased risk of AKI if the amount of GDF-15 is above about 3389 pg/ml.   
     
     
         11 . The method of  claim 10 , wherein the surgical procedure is orthopedic surgery, a tumor resection, surgery of the gastrointestinal tract not involving tumor resection, or cardiac surgery. 
     
     
         12 . The method of  claim 10 , wherein the sample is obtained from the patient immediately after surgery or less than 1 day, 2 days, or 3 days after the patient undergoes the surgical procedure. 
     
     
         13 . The method of  claim 10 , wherein the ligand comprising specific binding affinity for GDF-15 is an antibody, nucleic acid, receptor, binding partner, or aptamer. 
     
     
         14 . The method of  claim 10 , wherein the amount of GDF-15 in the sample is determined by measuring a signal obtained from GDF-15, wherein the intensity of the signal directly correlates with the number of molecules of GDF-15 in the sample. 
     
     
         15 . The method of  claim 10 , wherein the amount of GDF-15 in the sample is determined by measuring a signal obtained from a secondary component, wherein the intensity of the signal indirectly correlates with the number of molecules of GDF-15 in the sample. 
     
     
         16 . The method of  claim 10 , wherein the patient is predicted to have an increased risk of AKI requiring hemodialysis if the amount of GDF-15 is above about 6393 pg/ml. 
     
     
         17 . The method of  claim 10 , further comprising contacting, in vitro, the sample obtained from the patient after the patient undergoes the surgical procedure with a second ligand comprising specific binding affinity for troponin T; determining the amount of troponin T in the sample; and providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1807 pg/ml and the amount of troponin T is below about 312.4 pg/ml, or that the patient has an increased risk of AKI if the amount of GDF-15 is above about 3389 pg/ml and the amount of troponin T is above about 503.6 pg/ml. 
     
     
         18 . The method of  claim 10 , further comprising contacting, in vitro, the sample obtained from the patient after the patient undergoes the surgical procedure with a second ligand comprising specific binding affinity for NT-proBNP; determining the amount of NT-proBNP in the sample; and providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1807 pg/ml and the amount of NT-proBNP is below about 368.6 pg/ml, or that the patient has an increased risk of AKI if the amount of GDF-15 is above about 3389 pg/ml and the amount of NT-proBNP is above about 924.6 pg/ml. 
     
     
         19 . The method of  claim 10 , further comprising contacting, in vitro, the sample obtained from the patient after the patient undergoes the surgical procedure with a second ligand comprising specific binding affinity for troponin T and a third ligand comprising specific binding affinity for NT-proBNP; determining the amounts of troponin T and NT-proBNP in the sample; and providing a prediction that the patient is not at risk of AKI if the amount of GDF-15 is below about 1807 pg/ml, the amount of troponin T is below about 312.4 pg/ml, and the amount of NT-proBNP is below about 368.6 pg/ml; or that the patient has an increased risk of AKI if the amount of GDF-15 is above about 3389 pg/ml, the amount of troponin T is above about 503.6 pg/ml, and the amount of NT-proBNP is above about 924.6 pg/ml. 
     
     
         20 . A device for predicting a risk of acute kidney injury (AKI) in a patient subjected to a surgical procedure, comprising:
 a) an analyzing unit comprising means for contacting, in vitro, a sample obtained from the patient before or after the patient undergoes the surgical procedure with a ligand comprising specific binding affinity for GDF-15, and means for determining the amount of GDF-15 in the sample; and   b) an evaluation unit comprising a computer for comparing the determined amount of GDF-15 with a reference amount, predicting the risk of AKI during or immediately after the surgical procedure, and providing an output indicating the risk of AKI.