Prognostic assays for maintenance hemodialysis patients

• US 10,473,675 B2
• Filed: 04/07/2017
• Issued: 11/12/2019
• 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-Zadeh, Kamyar, Caulfield, Michael P., Salameh, Wael A.
• Primary Examiner(s): Fritchman, Rebecca M
• Application Number:
  US15/481,664
• Publication Number:
  US 20170343568A1
• Time in Patent Office: 949 Days
• Field of Search: 73 6141
• 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 sample from a MEM patient,

b. irradiating the lipoprotein particles with alpha radiation and fractionating the lipoprotein particles according to particle diameter using ion mobility fractionation,

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

d. identifying the patient as having reduced risk of mortality when the sample 1-LDL concentration is greater than a reference 1-LDL concentration or identifying the patient as having no change in the risk of mortality when the sample 1-LDL concentration is less than the reference 1-LDL concentration.

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

3. The method of claim 1, wherein the sample is selected from the group consisting of whole blood, serum, and plasma.

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

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

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

7. The method of claim 1, wherein the sample 1-LDL concentration is measured by ion mobility analysis.

8. The method of claim 1, further comprising the step of selecting a treatment regime based upon mortality risk of the patient.

9. 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 ion mobility lipoprotein fractionation,

c. determining the low density lipoprotein (LDL) particle concentrations by detecting and counting the fractionated lipoprotein particles having a particle diameter of 180.0-233.3 Å

in the sample from the patient,

d. determining a mean low density lipoprotein particle diameter (LDL-Pd) in the sample from the MHD patient based on the concentrations of LDL particles in the sample,

e. determining the total LDL concentration (LDL-C) in the sample, and

f. identifying the patient as having increased risk of mortality when the sample mean LDL-Pd is less than the reference LDL-Pd and the sample LDL-C is greater than a reference LDL-C, or identifying the patient as having no change in the risk of mortality when the sample LDL-Pd is greater than or equal to the reference LDL-Pd.

10. The method of claim 9, wherein the reference mean LDL particle size is about 216 Å

.

11. The method of claim 9, wherein the reference mean LDL particle size is about 219 Å

.

12. The method of claim 9, wherein the sample is selected from the group consisting of whole blood, serum, and plasma.

13. The method of claim 9, wherein the reference LDL particle size is derived from a control population of subjects not undergoing maintenance hemodialysis.

14. The method of claim 9, wherein the reference LDL particle size is the LDL particle size measured in the patient at an earlier time.

15. The method of claim 9, wherein the reference LDL particle size is the LDL particle size measured in the patient prior to receiving treatment.

16. The method of claim 9, wherein the sample LDL particle size is measured by ion mobility analysis.

17. The method of claim 9, further comprising the step of selecting a treatment regime based upon mortality risk of the patient.

18. The method of claim 9, wherein the reference LDL-C is the LDL-C measured in the patient at an earlier time.

19. The method of claim 9, wherein the reference LDL-C is the LDL-C measured in the patient prior to receiving treatment.

20. The method of claim 9, further comprising measuring the total particle concentration of low density lipoprotein (LDL-Pc) in the plasma sample.

21. The method of claim 9, 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.