Marker for early diagnosis of kidney failure

Abstract

The present invention addresses the problem of identifying a biomarker of renal failure, said biomarker being available from urine or blood, and fluctuating from an early stage than glomerular filtration rate and serum creatinine level, and thus developing a technique for diagnosing early stage kidney failure. A method for analyzing the blood, plasma, serum or urine of a renal failure suspected subject comprises a step of measuring the concentration of a pair of D-form and L-form of at least one amino acid selected from the amino acid group consisting of [D-serine] and [L-serine], etc., contained in the blood, plasma, serum or urine of the subject, and calculating, as an pathological index of the subject, the ratio of the D-form concentration to the L-form concentration or the percentage of the D-form concentration relative to the total concentration of the D-form and L-form.

1 .- 13 . (canceled) 
     
     
         14 . A method of diagnosing and treating a renal disease comprising obtaining a urine sample from a subject;
 measuring concentrations of a pair of D-form and L-form of at least one amino acid selected from the amino acid group consisting of D-asparagine and L-asparagine, D-proline and L-proline, D-alanine and L-alanine, and D-valine and L-valine in the urine sample of the subject;   calculating a value of a pathological index for the subject based on the measured concentrations of D-form and L-form of said at least one amino acid in the urine sample of the subject;   determining that the subject has the renal disease or is suspected of having an early stage of the renal disease if the calculated value of the pathological index for the subject is statistically reduced compared to a healthy individual group pathological index reference value; and   treating the renal disease in the subject who is determined to have the renal disease or is suspected of having an early stage of the renal disease, wherein said treating comprises drug administration, artificial dialysis or kidney transplantation   and wherein said drug is a renal disease therapeutic drug that controls the progression of the renal disease or improves the renal disease which is at least one selected from the group comprising antihypertensive drugs, antidiabetic drugs, antidyslipidemic drugs, antianemic drugs, therapeutic drugs for bone and mineral metabolic disorders, therapeutic drugs for hyperuricemia and therapeutic drugs for uremic toxins.   
     
     
         15 . The method of  claim 14 , the treating comprises inhibiting the progression or improving the renal disease. 
     
     
         16 . The method of  claim 14 , wherein the drug is at least one selected from the group comprising antihypertensive drugs, antidiabetic drugs, antidyslipidemic drugs, antianemic drugs, therapeutic drugs for bone and mineral metabolic disorders, therapeutic drugs for hyperuricemia, and therapeutic drugs for uremic toxins. 
     
     
         17 . The method of  claim 16 , wherein the drug is at least one selected from the group comprising angiotensin-converting enzymes, angiotensin II receptor antagonists, α-glucosidase inhibitors, insulin preparations, HMG-CoA reductase inhibitors, intestinal
 cholesterol transporter inhibitors, recombinant human erythropoietin preparations and spherical adsorbent carbon medications. 
 
     
     
         18 . The method of  claim 14 , wherein the drug is selected from a therapeutic drug for hyperkalemia and a therapeutic drug for hyperphosphatemia. 
     
     
         19 . The method of  claim 14 , wherein said determining comprises
 a) determining that the subject does not have the renal disease if the calculated value of the pathological index for the subject is statistically similar to a healthy individual group pathological index reference value;   b) determining that the subject has the renal disease if the calculated value of the pathological index for the subject is statistically similar to an acute or chronic renal disease patient pathological index reference value; and   c) determining that the subject is suspected of having an early stage of the renal disease if the calculated value of the pathological index for the subject is between a healthy individual group pathological index reference value and an acute or chronic renal disease patient pathological index reference value.   
     
     
         20 . The method of  claim 19 , wherein when the subject is determined to be suspected of having an early stage of the renal disease, the renal disease is improved or the progression of the renal disease is inhibited, before the subject exhibits blood creatinine level fluctuations. 
     
     
         21 . The method of  claim 19 , wherein the drug is selected from the group comprising antihypertensive drugs, antidiabetic drugs, antidyslipidemic drugs, antianemic drugs, therapeutic drugs for bone and mineral metabolic disorders, therapeutic drugs for hyperuricemia, and therapeutic drugs for uremic toxins. 
     
     
         22 . The method of  claim 21 , wherein the drug is at least one selected from the group comprising angiotensin-converting enzymes, angiotensin II receptor antagonists, α-glucosidase inhibitors, insulin preparations, HMG-CoA reductase inhibitors, intestinal cholesterol transporter inhibitors, recombinant human erythropoietin preparations and spherical adsorbent carbon medications. 
     
     
         23 . The method of  claim 19 , wherein the drug is selected from a therapeutic drug for hyperkalemia and a therapeutic drug for hyperphosphatemia. 
     
     
         24 . The method of  claim 22 , which does not comprise measuring a volume of the urine sample and wherein said calculating does not comprise correcting for the volume of the urine sample. 
     
     
         25 . The method of  claim 24 , wherein said calculating comprises:
 calculating a ratio between the measured concentration of D-asparagine and the measured concentration of L-asparagine or calculating a ratio between the measured concentration of D-asparagine and a sum of the measured concentration of D-asparagine and the measured concentration of L-asparagine, or   calculating a ratio between the measured concentration of D-proline and the measured concentration of L-proline or calculating a ratio between the measured concentration of D-proline and a sum of the measured concentration of D-proline and the measured concentration of L-proline, or   calculating a ratio between the measured concentration of D-alanine and the measured concentration of L-alanine or calculating a ratio between the measured concentration of D-alanine and a sum of the measured concentration of D-alanine and the measured concentration of L-alanine, or   calculating a ratio between the measured concentration of D-valine and the measured concentration of L-valine or calculating a ratio between the measured concentration of D-valine and a sum of the measured concentration of D-valine and the measured concentration of L-valine.   
     
     
         26 . The method of  claim 22 , further comprising measuring a pair of concentrations of D-form and L-form of amino acids other than asparagine, proline, alanine, or valine, using a pathological index calculated from the pair of concentrations in combination with said pathological index to determine that the subject has renal disease or is suspected of having an early stage of renal disease. 
     
     
         27 . The method of  claim 22 , wherein said measuring is performed by a separation analysis system comprising an enantiomer selective column. 
     
     
         28 . The method of  claim 26 , wherein said measuring steps are performed by a separation analysis system comprising an enantiomer selective column. 
     
     
         29 . The method of  claim 27 , wherein the separation analysis system is a HPLC system. 
     
     
         30 . The method of  claim 28 , wherein the separation analysis system is a HPLC system.