PROGNOSTIC ASSAYS FOR MAINTENANCE HEMODIALYSIS PATIENTS

• US 20200132702A1
• Filed: 10/29/2019
• Published: 04/30/2020
• Est. Priority Date: 11/01/2010
• Status: Active Grant

• Current Assignee: Quest Diagnostics Investments Incorporated (Quest Diagnostics Incorporated)
• Original Assignee: Quest Diagnostics Investments Incorporated (Quest Diagnostics Incorporated)
• Inventors: Kalantar-Zedeh, Kamyar, Caulfield, Michael P., Salameh, Wael A.
• Granted Patent: US 11,137,410 B2
• Time in Patent Office: Days
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

Described herein are methods for determining the overall survival of maintenance hemodialysis patients. The methods include measuring low density lipoprotein (LDL) particle size and subfraction concentrations as prognostic tools for early mortality risk detection. For example, the presence of increased very small LDL concentration or decreased LDL particle size in blood-serum serves as a useful means for prognostic risk assessment and monitoring.

Claims

1-30. -30. (canceled)

31. A method for risk-stratification in a maintenance hemodialysis (MHD) patient comprising:

a) separating lipoprotein particles from non-lipoprotein particles in a plasma sample from an MHD patient;

b) irradiating with alpha radiation and fractionating the lipoprotein particles according to particle diameter using on mobility lipoprotein fractionation;

c) classifying the fractionated lipoprotein particles into one or more subfractions according to the following ranges;

(i) 76.5-105.0 Å

as high density lipoprotein (HDL) small,

(ii) 105.0-145.0 as Å

HDL large;

(iii) 180.0-208.2 Å

as low density lipoprotein (LDL) very small,

(iv) 208.2-214.1 Å

as LDL small,

(v) 214.1-220.0 Å

as LDL medium,

(vi) 220.0-233.3 Å

as LDL large,

(vii) 233.0-250.0 Å and

intermediate density lipoprotein (IDL),

(viii) 250.0-296.0 Å

as IDL large,

(ix) 296.0-335.0 Å

as very low density lipoprotein (VLDL) small,

(x) 335.0-424.0 Å

as VLDL medium, and

(xi) 424.0-520.0 Å

as VLDL large; and

d) measuring the concentration of lipoprotein particles in each subfraction of (c).

32. The method of claim 31, further comprising determining the risk of mortality in the MHD based on the concentrations of lipoprotein particles in each subfraction.

33. The method of claim 32, wherein the concentations of lipoprotein particles in each subfraction are compared to a reference particle concentration.

34. The method of claim 33, wherein the reference vs-LDL particle concentration level is about 121 nmol/L.

35. The method of claim 33, wherein the reference vs-LDL particle concentration is derived from a control population of subjects not undergoing maintenance hemodialysis.

36. The method of claim 33, wherein the reference vs-LDL particle concentration is the vs-LDL particle concentration measured in the patient at an earlier time.

37. The method of claim 33, wherein the reference vs-LDL particle concentration is the vs-LDL particle concentration measured in the patient prior to receiving treatment.

38. The method of claim 33, wherein reference l-LDL particle concentration is about 105 nmol/L.

39. The method of claim 33, wherein the reference l-LDL particle concentration is derived from a control population of subjects not undergoing maintenance hemodialysis.

40. The method of claim 33, wherein the reference l-LDL particle concentration is the l-LDL concentration measured in a plasma sample from the patient at an earlier time.

41. The method of claim 33, wherein the reference l-LDL particle concentration is the l-LDL concentration measured in a plasma sample from the patient prior to receiving treatment.

42. The method of claim 31, further comprising determining a l-LDL:

s-LDL ratio.

43. The method of claim 42, further comprising comparing the l-LDL:

s-LDL ratio to a reference l-LDL;

s-LDL ratio.

44. The method of claim 43, wherein the reference l-LDL:

s-LDL ratio is about 0.90-1.05.

45. The method of claim 43, wherein the reference l-LDL:

s-LDL ratio is derived from a control population of subjects not undergoing maintenance hemodialysis.

46. The method of claim 43, wherein the reference l-LDL:

s-LDL ratio is the l-LDL;

s-LDL ratio measured in a plasma sample from the patient at an earlier time.

47. The method of claim 43, wherein the reference l-LDL:

s-LDL ratio is the l-LDL;

s-LDL ratio measured in a plasma sample from the patient prior to receiving treatment.

48. The method of claim 31, further comprising measuring the total concentration of low density lipoprotein (LDL-C) and/or the mean low density lipoprotein diameter (LDL-Pc) in the plasma sample.

49. The method of claim 31, further comprising measuring the total concentration of high density lipoprotein (HDL-C) and/or the mean high density lipoprotein diameter (HDL-Pc) in the plasma sample.