Means and Methods for Determining a Clearance Normalized Amount of a Metabolite Disease Biomarker in a Sample

• US 20160047829A1
• Filed: 10/16/2013
• Published: 02/18/2016
• Est. Priority Date: 10/18/2012
• Status: Abandoned Application

• Current Assignee: Metanomics Gmbh (BASF SE), Ruprecht-Karls-Universitã¤T Heidelberg
• Original Assignee: Metanomics Gmbh (BASF SE), Ruprecht-Karls-Universitã¤T Heidelberg
• Inventors: Fuhrmann, Jens, Reszka, Regina, Weis, Tanja, Fischer, Jenny, Katus, Hugo A, Frey, Nobert, Sigl, Johanna
• Application Number:
  US14/435,952
• Publication Number:
  US 20160047829A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: G01N 2405/04 Phospholipids, i.e. phosphoglycerides
• CPC Class Codes: G01N 2405/08 Sphingolipids
• CPC Class Codes: G01N 2560/00 Chemical aspects of mass spectrometric analysis of biological material
• CPC Class Codes: G01N 2800/02 Nutritional disorders
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/2814 Dementia; Cognitive disorders
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/347 Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
• CPC Class Codes: G01N 33/50 Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q
• CPC Class Codes: G01N 33/62 involving urea
• CPC Class Codes: G01N 33/64 involving ketones
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

The present invention relates to a method for determining a clearance normalized amount of a metabolite disease biomarker in a sample including the steps of (a) determining the amount of the disease biomarker in at least a first type of sample of a subject suspected to suffer from the disease, (b) determining the amount of a kidney function biomarker which correlates with the glomerular filtration rate (GFR) in the said at least first type of sample, and (c) determining a clearance normalized amount for the metabolite disease biomarker by normalizing the amount determined for the metabolite disease biomarker in step (a) to the amount of the kidney function biomarker determined in step (b). Moreover, the invention also relates to a method for diagnosing a disease in a subject suspected to suffer therefrom and to a device for determining a clearance normalized amount of a metabolite disease biomarker in a sample.

Claims

1-14. -14. (canceled)

15. A method for determining a clearance normalized amount of a metabolite disease biomarker in a sample comprising the steps of:

(a) determining the amount of the metabolite disease biomarker in at least a first type of sample of a subject suspected to suffer from the disease;

(b) determining the amount of a kidney function biomarker which correlates with the glomerular filtration rate (GFR) in the said at least first type of sample; and

(c) determining a clearance normalized amount for the metabolite disease biomarker by normalizing the amount determined for the metabolite disease biomarker in step (a) to the amount of the kidney function biomarker determined in step (b),

wherein said sample is blood or a derivative thereof.

16. The method of claim 15, wherein said kidney function biomarker is selected from the group consisting of cystatin C.

17. The method of claim 15, wherein said metabolite disease biomarker is a biomarker for cardiovascular diseases or disorders, diabetes or metabolic syndrome or neurodegenerative diseases.

18. The method of claim 15, wherein said metabolite disease biomarker is a biomarker selected from any of tables 1 to 6 and 8 to 21.

19. The method of claim 15, wherein said normalizing in step (c) encompasses calculating a ratio of the amount determined for the metabolite disease biomarker in step (a) and the amount of the kidney function biomarker determined in step (b).

20. The method of claim 15, wherein steps (a) and (b) are additionally carried out for a second type of sample being different from the first type of sample and wherein said normalizing in step (c) encompasses calculating (i) a ratio of the amount determined for the metabolite disease biomarker in the first type and the second type samples, (ii) calculating a ratio of the kidney function biomarker determined in the first type and the second type samples, and (iii) calculating a ratio of the ratios calculated under (i) and (ii).

21. A method for diagnosing a disease in a subject suspected to suffer therefrom comprising:

(a) determining a clearance normalized amount for a metabolite disease biomarker in a sample of said subject according to the method of claim 15; and

(b) comparing said clearance normalized amount to a reference, whereby the disease is to be diagnosed.

22. The method of claim 21, wherein said disease is a cardiovascular diseases or disorders, diabetes or metabolic syndrome or neurodegenerative diseases.

23. The method of claim 21, wherein said metabolite disease biomarker is a biomarker selected from any of tables 1 to 6 and 8 to 21.

24. A device for determining a clearance normalized amount of a metabolite disease biomarker in a sample comprising:

(a) an analyzing unit comprising a detection agent which specifically detects the amount of at least one metabolite disease biomarker and a detection agent which specifically detects the amount of a kidney function biomarker; and

(b) an evaluation unit comprising a data processor having tangibly embedded a computer program code carrying out an algorithm which normalizes the amount for the metabolite disease biomarker to the amount of the kidney function biomarker.

25. The device of claim 24, wherein said normalization encompasses calculating a ratio of the amount determined for the metabolite disease biomarker in step (a) and the amount of the kidney function biomarker determined in step (b)

26. The device of claim 24, wherein said evaluation unit comprises a database with stored references which allow for diagnosing a disease based on the clearance normalized amount for the metabolite disease biomarker.