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 for diagnosing and treating a renal disease of a subject comprising:
 measuring an amount of an amino acid stereoisomer in a blood sample from a subject;   determining whether the subject has a renal disease is suspected of having an early stage of the renal disease based on the measured value of the amount of the amino acid stereoisomer and a reference value from a healthy individual, wherein the amino acid stereoisomer is selected from the group consisting of D-serine, D-threonine, D-alanine, D-asparagine, D-allo-threonine, D-glutamine, D-proline and D-phenylalanine, and   treating the renal disease in the subject who is determined to have renal disease or is suspected of having an early stage of renal disease,   wherein said treating comprises drug administration, artificial dialysis or kidney transplantation,   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 consisting of 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 , wherein the drug is at least one selected from the group consisting of 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. 
     
     
         16 . The method of  claim 14 , wherein said blood sample is a serum sample. 
     
     
         17 . The method of  claim 15 , wherein said blood sample is a serum sample. 
     
     
         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 15 , wherein the drug is selected from a therapeutic drug for hyperkalemia and a therapeutic drug for hyperphosphatemia. 
     
     
         20 . The method of  claim 14 , further comprising calculating a disease state index by substituting the measured amount of the amino acid stereoisomer into a discriminant equation; and wherein said determining comprises 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 disease state index is statistically different compared to a healthy individual group disease state index reference value. 
     
     
         21 . The method of  claim 15 , further comprising calculating a disease state index by substituting the measured amount of the amino acid stereoisomer into a discriminant equation; and wherein said determining comprises 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 disease state index is statistically different compared to a healthy individual group disease state index reference value. 
     
     
         22 . The method of  claim 20 , wherein the determining step comprises
 a) the subject has renal disease if the calculated value of the disease state index for the subject is statistically similar to a healthy individual group disease state index reference value;   b) the subject has renal disease if the calculated value of the disease state index for the subject is statistically similar to an acute or chronic renal disease patient disease state index reference value; and   c) the subject is suspected of having an early stage of renal disease if the calculated value of the disease state index for the subject is between a healthy individual group disease state index reference value and an acute or chronic renal disease patient disease state index reference value.   
     
     
         23 . The method of  claim 21 , wherein the determining step comprises
 a) the subject has renal disease if the calculated value of the disease state index for the subject is statistically similar to a healthy individual group disease state index reference value;   b) the subject has renal disease if the calculated value of the disease state index for the subject is statistically similar to an acute or chronic renal disease patient disease state index reference value; and   c) the subject is suspected of having an early stage of renal disease if the calculated value of the disease state index for the subject is between a healthy individual group disease state index reference value and an acute or chronic renal disease patient disease state index reference value.   
     
     
         24 . The method of  claim 20 , wherein when the subject is determined to be suspected of having an early stage of renal disease, the renal disease is improved or the progression of renal disease is controlled, before the subject exhibits blood creatinine level fluctuations. 
     
     
         25 . The method of  claim 21 , wherein when the subject is determined to be suspected of having an early stage of renal disease, the renal disease is improved or the progression of renal disease is controlled, before the subject exhibits blood creatinine level fluctuations 
     
     
         26 . The method of  claim 20 , which does not comprise measuring a volume of the blood sample and wherein said calculating does not comprise correcting for the volume of the blood sample. 
     
     
         27 . The method of  claim 21 , which does not comprise measuring a volume of the blood sample and wherein said calculating does not comprise correcting for the volume of the blood sample. 
     
     
         28 . The method of  claim 20 , wherein said calculating comprises calculating a ratio between the measured concentration of D-serine and the measured concentration of L-serine or calculating a ratio between the measured concentration of D-serine and a sum of the measured concentration of D-serine and the measured concentration of L-serine. 
     
     
         29 . The method of  claim 21 , wherein said calculating comprises calculating a ratio between the measured concentration of D-serine and the measured concentration of L-serine or calculating a ratio between the measured concentration of D-serine and a sum of the measured concentration of D-serine and the measured concentration of L-serine. 
     
     
         30 . The method of  claim 20 , further comprising measuring a pair of concentrations of D-form and L-form of amino acids other than serine, 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. 
     
     
         31 . The method of  claim 21 , further comprising measuring a pair of concentrations of D-form and L-form of amino acids other than serine, 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. 
     
     
         32 . The method of  claim 14 , wherein said measuring is performed by means of a separation analysis system comprising a chiral column. 
     
     
         33 . The method of  claim 32 , wherein the separation analysis system is a HPLC system.