Prognostic assays for maintenance hemodialysis patients

• US 9,638,705 B2
• Filed: 10/27/2011
• Issued: 05/02/2017
• Est. Priority Date: 11/01/2010
• Status: Active Grant

• Current Assignee: Los Angeles Biomedical Research Institute, Quest Diagnostics Investments Incorporated (Quest Diagnostics Incorporated)
• Original Assignee: Los Angeles Biomedical Research Institute, Quest Diagnostics Investments Incorporated (Quest Diagnostics Incorporated)
• Inventors: Kalantar-Zadeh, Kamyar, Caulfield, Michael P., Salameh, Wael A.
• Primary Examiner(s): Fritchman, Rebecca M
• Application Number:
  US13/283,536
• Publication Number:
  US 20120103072A1
• Time in Patent Office: 2,014 Days
• Field of Search: 204549, 204645, 73 6152, 702 19, 436 71
• 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. A method for predicting mortality risk 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. determining a very small low density lipoprotein (vs-LDL) particle concentration in the plasma sample by detecting and counting the fractionated lipoprotein particles having a particle diameter of 180.0-208.2 A;

d. determining a large low density lipoprotein (1-LDL) particle concentration in the plasma sample by detecting and counting the fractionated lipoprotein particles having a particle diameter of 220.0-233.3 A; and

e. identifying the MHD patient as having;

i. increased risk of mortality when the sample vs-LDL particle concentration is greater than a reference vs-LDL particle concentration;

ii. reduced risk of mortality when the sample 1-LDL particle concentration is greater than a reference 1-LDL particle concentration;

or

iii. no change in the risk of mortality when the sample vs-LDL particle concentration is less than or equal to the reference vs-LDL particle concentration and the sample 1-LDL particle concentration is less than the reference 1-LDL concentration,

whereby a vs-LDL particle concentration in a plasma sample from a MHD patient that is greater than the reference vs-LDL particle concentration and a 1-LDL

particle concentration in a plasma sample from a MHD patient that is greater than the reference 1-LDL particle concentration indicates an reduced risk of mortality in the MHD patient.

2. The method of claim 1, wherein the reference vs-LDL particle concentration level is about 121 nmol/L.

3. The method of claim 1, wherein the reference vs-LDL particle concentration is derived from a control population of subjects not undergoing maintenance hemodialysis.

4. The method of claim 1, wherein the reference vs-LDL particle concentration is the vs-LDL particle concentration measured in the patient at an earlier time.

5. The method of claim 1, wherein the reference vs-LDL particle concentration is the vs-LDL particle concentration measured in the patient prior to receiving treatment.

6. The method of claim 1, wherein reference l-LDL particle concentration is about 105 nmol/L.

7. The method of claim 1, wherein the reference l-LDL particle concentration is derived from a control population of subjects not undergoing maintenance hemodialysis.

8. The method of claim 1, wherein the reference l-LDL particle concentration is the l-LDL concentration measured in a plasma sample from the patient at an earlier time.

9. The method of claim 1, wherein the reference l-LDL particle concentration is the l-LDL concentration measured in a plasma sample from the patient prior to receiving treatment.

17. The method of claim 1, further comprising measuring the total concentration of low density lipoprotein (LDL-C) and/or the total particle concentration of low density lipoprotein (LDL-Pc) in the plasma sample.

18. The method of claim 1, further comprising measuring the total concentration of high density lipoprotein (HDL-C), the total particle concentration of high density lipoprotein (HDL-Pc), the concentration of very low density lipoprotein (VLDL) and/or intermediate density lipoprotein (IDL) in the plasma sample.

10. A method for predicting mortality risk 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. determining a small low density lipoprotein (s-LDL) particle concentration in the plasma sample by detecting and counting the fractionated lipoprotein particles having a particle diameter of 208.2-214.1 A;

d. determining a large low density lipoprotein (1-LDL) particle concentration in the plasma sample by detecting and counting the fractionated lipoprotein particles having a particle diameter of 220.0-233.3 A;

e. determining a ratio of the sample 1-LDL particle concentration to the sample s-LDL particle concentration, and

f. identifying the MHD patient as having reduced risk of mortality when the sample l-LDL;

s-LDL ratio is greater than a reference l-LDL;

s-LDL ratio or identifying the MHD patient as having no change in the risk of mortality when the reference LDL;

s-LDL ratio is less than the reference ratio.

11. The method of claim 10, wherein the reference l-LDL:

s-LDL ratio is about 0.90-1.05.

12. The method of claim 10, wherein the reference l-LDL:

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

13. The method of claim 10, 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.

14. The method of claim 10, 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.

15. The method of claim 10, further comprising measuring the total concentration of low density lipoprotein (LDL-C) and/or the total particle concentration of low density lipoprotein (LDL-Pc) in the plasma sample.

16. The method of claim 10, further comprising measuring the total concentration of high density lipoprotein (HDL-C), the total particle concentration of high density lipoprotein (HDL-Pc), the concentration of very low density lipoprotein (VLDL) and/or intermediate density lipoprotein (IDL) in the plasma sample.