Methods and Compositions for Monitoring and Risk Prediction in Cardiorenal Syndrome

Abstract

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects. In particular, the invention relates to methods and compositions selected to monitor cardiorenal syndrome using assays that detect NGAL, preferably together with assays that detect natriuretic peptides such as BNP. Such methods and compositions can provide early indications of a deterioration in cardiorenal syndrome status, including prognosis regarding mortality and worsening renal function.

We claim: 
     
         1 . A method of assigning a risk of worsening renal function to a patient suffering from heart failure, comprising:
 performing an assay method that detects NGAL on a body fluid sample obtained from said patient, thereby providing an NGAL assay result;   comparing said NGAL assay result to a baseline NGAL result; and   relating the NGAL assay result to the patient's risk of worsening renal function by assigning an increased risk of worsening renal function to said patient when said NGAL assay result is greater than said baseline NGAL result, relative to a risk assigned when said NGAL assay result is less than said baseline NGAL result, or by assigning a decreased risk of worsening renal function to said patient when said NGAL assay result is less than said baseline NGAL result, relative to a risk assigned when said NGAL assay result is greater than said baseline NGAL result.   
     
     
         2 . A method according to  claim 1 , wherein said baseline NGAL result is determined by performing an assay method that detects NGAL on a body fluid sample obtained from said patient at a time earlier than the time at which the body fluid sample used to provide said NGAL assay result was obtained. 
     
     
         3 . A method according to  claim 1 , wherein said baseline NGAL result is determined from a population of subjects suffering from heart failure, and said baseline NGAL result is selected to separate said population into a first subpopulation having an increased risk of worsening renal function relative to a second subpopulation. 
     
     
         4 . A method according to  claim 3 , wherein said baseline NGAL result separates said first subpopulation from said second subpopulation with an odds ratio of at least 2 or more or 0.5 or less. 
     
     
         5 . A method according to  claim 3 , wherein said baseline NGAL result separates said first subpopulation from said second subpopulation with an odds ratio of at least 3 or more or 0.33 or less. 
     
     
         6 . A method according to  claim 1 , wherein the assay method comprises performing an immunoassay that detects NGAL. 
     
     
         7 . A method according to  claim 1 , wherein the body fluid sample is selected from the group consisting of urine, blood, serum, and plasma. 
     
     
         8 . A method according to  claim 6 , wherein said immunoassay comprises contacting said body fluid sample with a solid phase comprising antibody that detects NGAL, and detecting binding to said antibody. 
     
     
         9 . A method according to  claim 1 , wherein the method further comprises determining one or more additional variables selected from the group consisting of a serum creatinine level for said patient, a creatinine clearance rate for said patient, a cystatin C level for said patient, and a glomerular filtration rate for said patient; and
 wherein the patient's risk of worsening renal function is assigned based on comparing said NGAL assay result to said baseline NGAL result, and on said one or more additional variables.   
     
     
         10 . A method according to  claim 1 , wherein the method further comprises determining one or more additional variables selected from the group consisting of a urine output level for said patient, age of said patient, the presence or absence of diabetes in said patient, and the presence or absence of hypertension in said patient; and
 wherein the patient's risk of worsening renal function is assigned based on comparing said NGAL assay result to said baseline NGAL result, and on said one or more additional variables.   
     
     
         11 . A method of assigning a mortality risk to a patient suffering from renal dysfunction, comprising:
 performing an assay method that detects NGAL on a body fluid sample obtained from said patient, thereby providing an NGAL assay result;   comparing said NGAL assay result to a baseline NGAL result; and   relating the NGAL assay result to the patient's mortality risk by assigning an increased mortality risk to said patient when said NGAL assay result is greater than said baseline NGAL result, relative to a risk assigned when said NGAL assay result is less than said baseline NGAL result, or by assigning a decreased mortality risk to said patient when said NGAL assay result is less than said baseline NGAL result, relative to a risk assigned when said NGAL assay result is greater than said baseline NGAL result.   
     
     
         12 . A method according to  claim 11 , wherein said baseline NGAL result is determined by performing an assay method that detects NGAL on a body fluid sample obtained from said patient at a time earlier than the time at which the body fluid sample used to provide said NGAL assay result was obtained. 
     
     
         13 . A method according to  claim 11 , wherein said baseline NGAL result is determined from a population of subjects suffering from renal dysfunction, and said baseline NGAL result is selected to separate said population into a first subpopulation having an increased mortality risk relative to a second subpopulation. 
     
     
         14 . A method according to  claim 13 , wherein said baseline NGAL result separates said first subpopulation from said second subpopulation with an odds ratio of at least 2 or more or 0.5 or less. 
     
     
         15 . A method according to  claim 13 , wherein said baseline NGAL result separates said first subpopulation from said second subpopulation with an odds ratio of at least 3 or more or 0.33 or less. 
     
     
         16 . A method according to  claim 11 , wherein the assay method comprises performing an immunoassay that detects NGAL. 
     
     
         17 . A method according to  claim 11 , wherein the body fluid sample is selected from the group consisting of urine, blood, serum, and plasma. 
     
     
         18 . A method according to  claim 16 , wherein said immunoassay comprises contacting said body fluid sample with a solid phase comprising antibody that detects NGAL, and detecting binding to said antibody. 
     
     
         19 . A method according to  claim 11 , wherein the method further comprises determining one or more additional variables selected from the group consisting of a serum creatinine level for said patient, a creatinine clearance rate for said patient, a cystatin C level for said patient, and a glomerular filtration rate for said patient; and
 wherein the patient's mortality risk is assigned based on comparing said NGAL assay result to said baseline NGAL result, and on said one or more additional variables.   
     
     
         20 . A method according to  claim 11 , wherein the method further comprises determining one or more additional variables selected from the group consisting of a urine output level for said patient, age of said patient, the presence or absence of diabetes in said patient, and the presence or absence of hypertension in said patient; and
 wherein the patient's mortality risk is assigned based on comparing said NGAL assay result to said baseline NGAL result, and on said one or more additional variables.   
     
     
         21 . A method according to  claim 11 , wherein the method further comprises:
 performing an assay method that detects one or more of BNP, NT-proBNP and proBNP on a body fluid sample obtained from said patient, thereby providing a natriuretic peptide assay result;   comparing said natriuretic peptide assay result to a baseline natriuretic peptide result; and   relating the natriuretic peptide assay result to the patient's mortality risk by assigning an increased mortality risk to said patient when said natriuretic peptide assay result is greater than said baseline natriuretic peptide result, relative to a risk assigned when said natriuretic peptide assay result is less than said baseline natriuretic peptide result, or by assigning a decreased mortality risk to said patient when said natriuretic peptide assay result is less than said baseline natriuretic peptide result, relative to a risk assigned when said natriuretic peptide assay result is greater than said baseline natriuretic peptide result.   
     
     
         22 . A method according to  claim 21 , wherein the assay method providing the natriuretic peptide assay result and the assay method providing the NGAL assay result are performed on the same body fluid sample obtained from said patient. 
     
     
         23 . A method of monitoring cardiorenal syndrome a patient, comprising:
 performing an assay method that detects NGAL on a body fluid sample obtained from said patient, thereby providing an NGAL assay result;   performing an assay method that detects one or more of BNP, NT proBNP and proBNP on the same or a different body fluid sample obtained from said patient, thereby providing a natriuretic peptide assay result; and   relating the NGAL assay result and the natriuretic peptide assay result to the patient's cardiorenal syndrome status by
 comparing said NGAL assay result to a baseline NGAL result, and assigning a worsening cardiorenal syndrome status to said patient when said NGAL assay result is greater than said baseline NGAL result, relative to a status assigned when said NGAL assay result is less than said baseline NGAL result, or by assigning an improving cardiorenal syndrome status to said patient when said NGAL assay result is less than said baseline NGAL result, relative to a status assigned when said NGAL assay result is greater than said baseline NGAL result, and 
 comparing said natriuretic peptide assay result to a baseline natriuretic peptide result, and assigning a worsening cardiorenal syndrome status to said patient when said natriuretic peptide assay result is greater than said baseline natriuretic peptide result, relative to a status assigned when said natriuretic peptide assay result is less than said baseline natriuretic peptide result, or by assigning an improving cardiorenal syndrome status to said patient when said natriuretic peptide assay result is less than said baseline natriuretic peptide result, relative to a status assigned when said natriuretic peptide assay result is greater than said baseline natriuretic peptide result. 
   
     
     
         24 . A method according to  claim 23 , wherein said baseline NGAL result is determined by performing an assay method that detects NGAL on a body fluid sample obtained from said patient at a time earlier than the time at which the body fluid sample used to provide said NGAL assay result was obtained. 
     
     
         25 . A method according to  claim 23 , wherein said baseline natriuretic peptide result is determined by performing an assay method that detects one or more of BNP, NT-proBNP and proBNP on a body fluid sample obtained from said patient at a time earlier than the time at which the body fluid sample used to provide said natriuretic peptide assay result was obtained. 
     
     
         26 . A method according to  claim 23 , wherein said baseline NGAL result is determined from a population of subjects suffering from cardiorenal syndrome, and said baseline NGAL result is selected to separate said population into a first subpopulation having a worsening cardiorenal syndrome status relative to a second subpopulation. 
     
     
         27 . A method according to  claim 23 , wherein said baseline natriuretic peptide result is determined from a population of subjects suffering from cardiorenal syndrome, and said baseline natriuretic peptide result is selected to separate said population into a first subpopulation having an worsening cardiorenal syndrome relative to a second subpopulation. 
     
     
         28 . A method according to  claim 26 , wherein said baseline NGAL result separates said first subpopulation from said second subpopulation with an odds ratio of at least 2 or more or 0.5 or less. 
     
     
         29 . A method according to  claim 26 , wherein said baseline NGAL result separates said first subpopulation from said second subpopulation with an odds ratio of at least 3 or more or 0.33 or less. 
     
     
         30 . A method according to  claim 27 , wherein said baseline natriuretic peptide result separates said first subpopulation from said second subpopulation with an odds ratio of at least 2 or more or 0.5 or less. 
     
     
         31 . A method according to  claim 27 , wherein said baseline natriuretic peptide result separates said first subpopulation from said second subpopulation with an odds ratio of at least 3 or more or 0.33 or less. 
     
     
         32 . A method according to  claim 23 , wherein the assay method that detects NGAL comprises performing an immunoassay that detects NGAL, and the assay method that detects one or more of BNP, NT-proBNP and proBNP comprises performing an immunoassay that detects one or more of BNP, NT-proBNP and proBNP. 
     
     
         33 . A method according to  claim 23 , wherein the body fluid sample is selected from the group consisting of urine, blood, serum, and plasma.