Kidney disease prognosis prediction method and system

Patent metadata

Field	Value
Publication number	US-11099191-B2
Application number	US-201716302226-A
Country	US
Kind code	B2
Filing date	May 17, 2017
Priority date	May 17, 2016
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

The purpose of the present invention is to provide: a method for predicting the prognosis for kidney disease for a subject on the basis of the amount of D- and L-amino acids, from a blood sample; and an analysis system that determines prognosis predictions. This purpose is achieved by using at least one amino acid to predict the prognosis for kidney disease, said amino acid being selected from the group consisting of D-serine, D-asparagine, D-proline, D-alanine, D-leucine, D-lysine, D-allo-isoleucine, L-glutamic acid, L-alanine, L-tryptophan, and L-asparagine.

First claim

The invention claimed is:

1. A method for prognosing an end stage kidney disease requiring renal replacement and treating a subject who has a prognosis of the end stage kidney disease and who has not been subjected to a dialysis, comprising:
measuring an amount of at least one D-amino acid selected from the group consisting of D-serine, D-asparagine, D-proline, D-alanine, D-leucine, D-lysine, D-allo-isoleucine in a blood sample of the subject,
measuring an amount of one or more of creatinine, urinary protein and cystatin C in the subject;

and
correlating (a) an index value based on the measured amount of the at least one D-amino acid according to a cutoff value for the index value and (b) the measured amount of the one or more of creatinine, urinary protein and cystatin C with a prognosis of the end stage kidney disease for the subject;
identifying the subject with (a) the index value based on the measured amount of the at least one D-amino acid being higher than the cutoff value for the respective D-amino acid and (b) the measured amount of the one or more of creatinine, urinary protein and cystatin C indicating the end stage kidney disease as a subject with a prognosis for the end stage kidney disease; and
administering to the subject with the prognosis for the end stage kidney disease
a treatment selected from the group consisting of dialysis, kidney transplant, lifestyle improvement, dietary counseling, blood pressure management, blood sugar management and lipid management.

2. The method according to claim 1 , wherein the cutoff value is predetermined by a Kaplan-Meier curve analysis.

3. The method according to claim 2 , wherein the cutoff value is 5.6 μmol/L for D-serine, 0.7 μmol/L for D-asparagine, 4.7 μmol/L for D-proline, 5.2 μmol/L for D-alanine, 0.5 μmol/L for D-leucine, 0.6 μmol/L for D-lysine, 0.1 μmol/L for D-alloisoleucine.

4. The method according to claim 1 , further comprising measuring an amount of an isomer corresponding to the at least one D-amino acid, wherein the index value is the ratio of the amount of the at least one D-amino acid to the amount of the corresponding isomer.

5. The method according to claim 1 , wherein the index value is further adjusted for one or more variables selected from the group consisting of eGFR, urinary protein level, diabetes, age, gender, hemoglobin level, mean blood pressure, history of cardiovascular events and presence or absence of anti-hypertensive drug treatment.

6. The method according to claim 1 , wherein said administering comprises administering to the subject with the prognosis for the end stage kidney disease an ACE inhibitor or ARB.

7. The method according to claim 1 , wherein said administering comprises administering to the subject with the prognosis for the end stage kidney disease insulin.

8. The method according to claim 1 , wherein said administering comprises administering to the subject with the prognosis for the end stage kidney disease a hyperlipidemia drug.

9. A method for prognosing an end stage kidney disease requiring renal replacement and treating a subject who has a prognosis of the end stage kidney disease and who has not been subjected to a dialysis, comprising:
measuring an amount of each of D-serine, D-asparagine, D-proline, and D-alanine in a blood sample of the subject, and
correlating an index value based on the measured amount of each of D-serine, D-asparagine, D-proline, and D-alanine with a prognosis of the end stage kidney disease for the subject according to a cutoff value for the index value,
identifying the subject with the index value based on the measured amount of each of D-serine, D-asparagine, D-proline, and D-alanine being higher than the respective cutoff value for D-serine, D-asparagine, D-proline, and D-alanine as a subject with a prognosis for the end stage kidney disease; and
administering to the subject with the prognosis for the end stage kidney disease a treatment selected from the group consisting of dialysis, kidney transplant, lifestyle improvement, dietary counseling, blood pressure management, blood sugar management and lipid management.

10. The method of claim 9 , wherein said administering comprises administering to the subject with the prognosis for the end stage kidney disease an ACE inhibitor or ARB.

11. The method of claim 9 , wherein said administering comprises administering to the subject with the prognosis for the end stage kidney disease insulin.

12. The method of claim 9 , wherein said administering comprises administering to the subject with the prognosis for the end stage kidney disease a hyperlipidemia drug.

13. The method of claim 9 , wherein the cutoff value is predetermined by a Kaplan-Meier curve analysis.

14. The method of claim 13 , wherein the cutoff value is 5.6 μmol/L for D-serine, 0.7 μmol/L for D-asparagine, 4.7 μmol/L for D-proline, 5.2 μmol/L for D-alanine, 0.5 μmol/L for D-leucine, 0.6 μmol/L for D-lysine, 0.1 μmol/L for D-alloisoleucine.

15. The method of claim 1 , comprising measuring an amount of creatinine in the subject, wherein said correlating comprises correlating (a) the index value based on the measured amount of the at least one D-amino acid according to the cutoff value for the index value and (b) the measured amount of creatinine with the prognosis of the end stage kidney disease for the subject and said identifying is identifying the subject with (a) the index value based on the measured amount of the at least one D-amino acid being higher than the cutoff value for the respective D-amino acid and (b) the measured amount of creatinine indicating the end stage kidney disease as a subject with a prognosis for the end stage kidney disease.

16. The method of claim 1 , comprising measuring an amount of urinary protein in the subject, wherein said correlating comprises correlating (a) the index value based on the measured amount of the at least one D-amino acid according to the cutoff value for the index value and (b) the measured amount of urinary protein with the prognosis of the end stage kidney disease for the subject and said identifying is identifying the subject with (a) the index value based on the measured amount of the at least one D-amino acid being higher than the cutoff value for the respective D-amino acid and (b) the measured amount of urinary protein indicating the end stage kidney disease as a subject with a prognosis for the end stage kidney disease.

17. The method of claim 1 , comprising measuring an amount of cystatin C in the subject, wherein said correlating comprises correlating (a) the index value based on the measured amount of the at least one D-amino acid according to the cutoff value for the index value and (b) the measured amount of cystatin C with the prognosis of the end stage kidney disease for the subject and said identifying is identifying the subject with (a) the index value based on the measured amount of the at least one D-amino acid being higher than the cutoff value for the respective D-amino acid and (b) the measured amount of cystatin C indicating the end stage kidney disease as a subject with a prognosis for the end stage kidney disease.

18. The method of claim 9 , further comprising measuring an amount of at least one creatinine, urinary protein and cystatin C in the subject, wherein said correlating comprises correlating (a) the index value based on the measured amount of each of D-serine, D-asparagine, D-proline, and D-alanine according to the cutoff value for the index value and (b) the measured amount of the one or more of creatinine, urinary protein and cysta

Assignees

• Univ Osaka
• Kagami Inc

Inventors

• Isaka Yoshitaka
• Kimura Tomonori
• Yasuda Keiko
• Hamase Kenji
• Mita Masashi

Classifications

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G16H50/20

  for computer-aided diagnosis, e.g. based on medical expert systems · CPC title

• G01N2800/347

  Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy · CPC title

• G16B20/00

  ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations · CPC title

• G01N33/68 Primary

  involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} · CPC title