Kidney disease biomarker

Patent metadata

Field	Value
Publication number	US-10444248-B2
Application number	US-201314421382-A
Country	US
Kind code	B2
Filing date	Aug 12, 2013
Priority date	Aug 13, 2012
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

The present invention provides a method of stratifying a patient suffering from CKD into one of stages 1-3 of CKD, comprising determining the level of the biomarkers FABP1, γ-GT, AST, creatinine and cystatin C in a sample obtained from the patient and comparing the level of FABP1 in the sample to a control value and the levels of γ-GT, AST, creatinine and cystatin C in the sample to a range of control values for each biomarker, wherein an increased level of FABP1 compared to the control value and levels of γ-GT, AST, creatinine and cystatin C within the range of control values for each biomarker indicate that the patient suffers from stage 1 CKD or wherein an increased level of FABP1 compared to the control value, levels of γ-GT and AST within the range of control values for each biomarker, and increased levels of creatinine and cystatin C compared to an upper threshold of the control range for these biomarkers indicate that the patient suffers from stage 2 or stage 3 CKD.

First claim

The invention claimed is:

1. A method of detecting biomarkers of stage 1, 2, 3 or greater of chronic kidney disease (CKD) in a patient suffering from CKD, comprising:
measuring the level of the biomarkers Fatty Acid-Binding Protein 1 (FABP1), gamma glutamyl transpeptidase (γ-GT), aspartate transaminase (AST), creatinine and cystatin C in a sample obtained from a patient suffering from CKD, and
determining whether the measured level for each of the biomarkers FABP1, γ-GT, AST, creatinine and cystatin C exceed a lower threshold of a range of control values for each biomarker, wherein at least the measured level for FABP1 exceeds the lower threshold of a range of control values for FABP1 and determining whether the measured levels of γ-GT, AST, creatinine and cystatin C are within the range of control values for each biomarker, or
wherein the measured levels of γ-GT and AST are within the range of control values for each biomarker, and the measured levels of creatinine and cystatin C exceed the upper threshold of the range of the control for values for these biomarkers, or
wherein the measured level of FABP1 exceeds the upper threshold of the range of control values of FABP1 and the measured levels of creatinine and cystatin C exceed the upper threshold of the range of the control values for these biomarkers.

2. The method of claim 1 , wherein the measured level of the biomarkers are adjusted by the use of a classification algorithm that is derived using logistic regression, decision trees, support vector machines, neural networks, random forest or another machine learning algorithm.

3. The method of claim 1 , wherein the sample is a serum sample.

4. The method of claim 1 , wherein detecting biomarkers of stage 1 or 2 of CKD, comprises measuring a level of FABP1 from around 15 ng/mL to 75 ng/ml (female) or 21 ng/mL to 151 ng/mL of the biomarkers (male),
wherein detecting biomarkers of Stage 3 or greater of CKD comprises measuring a level of FABP1 above around 75 ng/mL (female) or 151 ng/mL (male) of the biomarkers.

5. The method of claim 1 , wherein the patient has co-morbidity for a renal disease or injury selected from the group consisting of, but not limited to, chronic kidney disease (CKD), acute kidney injury (AKI), diabetic nephropathy, glomerulonephritis, focal glomerulosclerosis, immune complex nephropathy, lupus nephritis, drug-induced renal injury, or is characterized as nephrotic syndrome or renal insufficiency or is caused by kidney graft rejection.

6. The method of claim 1 , wherein the patient has metabolic syndrome.

7. The method of claim 1 , wherein the level of the biomarkers is measured comprising using a solid state device comprising a substrate having an activated surface on to which is immobilized an antibody to FABP1 in discreet areas of the activated surface.

8. The method of claim 7 , wherein the antibody to FABP1 is a monoclonal antibody.

9. The method of claim 7 , wherein the substrate has an activated surface on to which is immobilized an antibody to γ-GT or AST.

10. The method of claim 9 , wherein the antibody to γ-GT or AST is a monoclonal antibody.

11. The method of claim 7 , wherein the substrate has an activated surface on to which is immobilized an antibody to cystatin C or creatinine.

12. The method of claim 11 , wherein the antibody to cystatin C or creatinine is a monoclonal antibody.

13. The method of claim 9 , wherein the substrate has an activated surface on to which is immobilized an antibody to cystatin C or creatinine.

14. The method of claim 13 , wherein the antibody to cystatin C or creatinine is a monoclonal antibody.

15. The method of claim 7 , further comprising: indicating that the patient suffers from stage 1, 2, 3 or above of CKD based upon the measured level of the biomarkers.

16. A method of detecting biomarkers of stage 1, 2, 3 or greater of chronic kidney disease (CKD) in a patient suffering from CKD, comprising:
measuring the level of the biomarkers Fatty Acid-Binding Protein 1 (FABP1), gamma glutamyl transpeptidase (γ-GT), aspartate transaminase (AST), creatinine and cystatin C in a sample obtained from a patient suffering from CKD, and
determining whether the measured level for each of the biomarkers FABP1, γ-GT, AST, creatinine and cystatin C exceed a lower threshold of a range of control values for each biomarker, wherein at least the measured level for FABP1 exceeds the lower threshold of a range of control values for FABP1, and
wherein detecting biomarkers of stage 1 or 2 of CKD, further comprises measuring a level of FABP1 from around 15 ng/mL to 75 ng/ml (female) or 21 ng/mL to 151 ng/mL of the biomarkers (male), and
wherein detecting biomarkers of Stage 3 or greater of CKD comprises measuring a level of FABP1 above around 75 ng/mL (female) or 151 ng/mL (male) of the biomarkers.

17. A method of detecting biomarkers of stage 1, 2, 3 or greater of chronic kidney disease (CKD) in a patient suffering from CKD, comprising:
measuring the level of the biomarkers Fatty Acid-Binding Protein 1 (FABP1), gamma glutamyl transpeptidase (γ-GT), aspartate transaminase (AST), creatinine and cystatin C in a sample obtained from a patient suffering from CKD, and
determining whether the measured level for each of the biomarkers FABP1, γ-GT, AST, creatinine and cystatin C exceed a lower threshold of a range of control values for each biomarker, wherein at least the measured level for FABP1 exceeds the lower threshold of a range of control values for FABP1, and
indicating that the patient suffers from stage 1, 2, 3 or above of CKD based upon the measured level of the biomarkers,
wherein the level of the biomarkers is measured comprising using a solid-state device comprising a substrate having an activated surface on to which is immobilized an antibody to FABP1 in discreet areas of the activated surface.

Assignees

• Randox Laboratories Ltd

Inventors

• Mcconnell Ivan
• Fitzgerald Stephen Peter
• Lamont John
• Richardson Claran

Classifications

• G01N33/92

  involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} · CPC title

• C07K14/8139

  Cysteine protease (E.C. 3.4.22) inhibitors, e.g. cystatin · CPC title

• C12N9/104 Primary

  Aminoacyltransferases (2.3.2) · CPC title

• C07K14/475

  Growth factors; Growth regulators · CPC title

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title