Methods for Detecting Renal Disease

Abstract

The disclosure is directed to methods and apparatus for the determination, diagnosis, progression and prognosis of kidney disease and mortality associated with kidney disease. The disclosure includes methods for determining renal function, in particular estimating glomerular filtration rate (GFR), in an animal. GFR can be useful in the diagnosis and treatment of kidney disease or dysfunction. In various aspects, the disclosure is directed to the use of free symmetrical dimethylarginine (SDMA) and creatinine in blood samples from animals, in particular cats and dogs, to determine glomerular filtration rate and kidney disease.

1 . A method for estimating glomerular filtration (GFR) rate in an animal subject, the method comprising:
 measuring the concentration of free symmetrical dimethylarginine (SDMA) in a blood sample from the subject;   measuring the concentration of creatinine in a blood sample from the subject; and   comparing a value resulting from an equation comprising the product of the concentration of creatinine and the concentration of free SDMA to one or more standard values that correlate to glomerular filtration rate in the animal subject.   
     
     
         2 . The method of  claim 32 , wherein the anti-SDMA antibody has reactivity for ADMA of less than 25% of its reactivity for SDMA. 
     
     
         3 . The method of  claim 32 , wherein the anti-SDMA antibody has reactivity for ADMA of less than 10% of its reactivity for SDMA. 
     
     
         4 . The method of  claim 32 , wherein the anti-SDMA antibody has reactivity for ADMA of less than 5% of its reactivity for SDMA. 
     
     
         5 . The method of  claim 32 , wherein the anti-SDMA antibody has reactivity for ADMA of less than 1% of its reactivity for SDMA. 
     
     
         6 . The method of  claim 1 , wherein the equation comprises the inverse of the product of the concentration of creatinine and the concentration of free SDMA. 
     
     
         7 . The method of  claim 1 , wherein at least one of the concentration of creatinine and the concentration are free SDMA are weighted in the calculation. 
     
     
         8 . The method of  claim 1 , wherein the product of a first weighted value based upon the concentration of creatinine and a second weighed value based upon the concentration free SDMA is represented by the formula PROD=[CRE] P ×[SDMA] Q  wherein PROD is the product, [CRE] is the concentration of creatinine, [SDMA] is the concentration of SDMA, P provides the weight to give [CRE] in the formula, and Q provides the weight to give [SDMA] in the formula. 
     
     
         9 . The method of  claim 8 , wherein the one or more standard values correlate to the inverse of the product. 
     
     
         10 . The method of  claim 8 , wherein P is between about −5 and 0, but not including 0. 
     
     
         11 . The method of  claim 8 , wherein Q is between about −2.5 and 0, but not including 0. 
     
     
         12 . The method of  claim 1 , further comprising determining renal function, kidney disease or kidney dysfunction by comparing the GFR in the subject to the GFR in one or more healthy subjects. 
     
     
         13 . The method of  claim 1 , further comprising treating the animal for kidney disease or dysfunction when the GFR is statistically significantly less than the average GFR for a healthy population of the species of animal. 
     
     
         14 . The method of  claim 13 , wherein the GFR of the animal subject is statistically significantly less than the average GFR for the healthy population when a difference between the GFR of the animal and the GFR for the healthy population is greater than two standard deviations. 
     
     
         15 - 31 . (canceled) 
     
     
         32 . The method of  claim 1 , wherein the measuring the concentration of free SDMA comprises:
 contacting the sample with an anti-SDMA antibody, wherein the antibody is specific for free SDMA and has no or substantially no cross-reactivity with one or more compounds selected from the group consisting of asymmetrical dimethylarginine (ADMA), L-arginine, and N-methylarginine; and   detecting complexes of the anti-SDMA antibody and SDMA.   
     
     
         33 . The method of  claim 9 , where P=−1 and Q=−1. 
     
     
         34 . The method of  claim 9 , wherein P is −1.5 and Q=−0.25. 
     
     
         35 . A computing device for estimating glomerular filtration (GFR) rate in an animal subject, the device comprising a microprocessor comprising machine readable instructions, which, when executed, perform the following step: comparing a value resulting from an equation comprising the product of the concentration of creatinine and the concentration of free SDMA to one or more standard values that correlate to glomerular filtration rate in the animal subject. 
     
     
         36 . The computing device of  claim 35 , wherein the equation comprises the inverse of the product of the concentration of creatinine and the concentration of free SDMA. 
     
     
         37 . The computing device of  claim 35 , wherein at least one of the concentration of creatinine and the concentration are free SDMA are weighted in the calculation. 
     
     
         38 . The computing device of  claim 35 , wherein the product of a first weighted value based upon the concentration of creatinine and a second weighed value based upon the concentration free SDMA is represented by the formula PROD=[CRE] P ×[SDMA] Q  wherein PROD is the product, [CRE] is the concentration of creatinine, [SDMA] is the concentration of SDMA, P provides the weight to give [CRE] in the formula, and Q provides the weight to give [SDMA] in the formula. 
     
     
         39 . The computing device of  claim 38 , wherein the one or more standard values correlate to the inverse of the product. 
     
     
         40 . The computing device of  claim 38 , wherein P is between about −5 and 0, but not including 0. 
     
     
         41 . The computing device of  claim 38 , wherein Q is between about −2.5 and 0, but not including 0. 
     
     
         42 . The computing device of  claim 35 , further comprising determining renal function, kidney disease or kidney dysfunction by comparing the GFR in the subject to the GFR in one or more healthy subjects. 
     
     
         43 . The computing device of  claim 38 , where P=−1 and Q=−1. 
     
     
         44 . The computing device of  claim 38 , wherein P is −1.5 and Q=−0.25. 
     
     
         45 . The method of  claim 1 , wherein the subject is canine or feline.