High-Density Lipoprotein Lipidomics and Mortality in CKD

Area of Science:

• Nephrology
• Cardiovascular Research
• Lipidomics

Background:

• Patients with chronic kidney disease (CKD) exhibit dysfunctional high-density lipoprotein (HDL) particles lacking cardioprotective effects.
• Altered lipid composition of HDL may underlie these functional deficits and contribute to cardiovascular risk in CKD.

Purpose of the Study:

• To investigate the association between specific HDL lipids (ceramides, sphingomyelins, phosphatidylcholines) and all-cause mortality in patients with CKD.
• To identify potential novel cardiovascular risk factors within HDL particles in the context of CKD.

Main Methods:

• Utilized data from a longitudinal prospective cohort of adult patients with CKD (excluding dialysis/transplant).
• Isolated HDL particles via density gradient ultracentrifugation and quantified lipid abundance using liquid chromatography tandem mass spectrometry (LC-MS/MS).
• Employed Cox regression models adjusted for multiple confounders and controlled for false discovery rates (FDR).

Main Results:

• Over a median follow-up of 6.12 years, 168 deaths occurred.
• Increased relative abundance of HDL ceramides, long-chain fatty acid sphingomyelins, and saturated/monounsaturated phosphatidylcholines were significantly associated with higher all-cause mortality risk (FDR < 5%).
• Sphingomyelins with very long fatty acids showed a trend towards lower mortality risk.

Conclusions:

• Specific HDL lipid classes, including ceramides and certain phosphatidylcholines, are associated with increased all-cause mortality risk in CKD patients.
• These findings suggest that the altered lipid composition of HDL particles may represent a novel cardiovascular risk factor in CKD.
• Further research is needed to explore the precise mechanisms and clinical implications of these HDL lipid alterations.