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Abstract: SA-PO929

High-Density Lipoprotein Lipidomics and Risk of Mortality in CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

  • Lidgard, Benjamin, University of Washington, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Zelnick, Leila R., University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
  • Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Fretts, Amanda M., University of Washington, Seattle, Washington, United States
  • Lemaitre, Rozenn, University of Washington, Seattle, Washington, United States
  • Bansal, Nisha, University of Washington, Seattle, Washington, United States
Background

Patients with CKD are at higher risk for mortality compared to the general population. Abnormalities in the structure and function of high-density lipoprotein (HDL) may contribute to this increased risk. We isolated HDL and utilized targeted lipidomics to identify its ceramide, sphingomyelin, and phosphatidylcholine components in participants with CKD and examined adjusted associations between these lipids and mortality.

Methods

We studied 498 participants with CKD from the Seattle Kidney Study. In each participant, HDL was isolated from serum, and targeted lipidomics were used to identify levels of various ceramides, sphingomyelins, and phosphatidylcholines composing HDL. We evaluated the associations between each lipid and mortality using Cox regression adjusted for potential confounders, accounting for multiple comparisons at a false discovery rate of 5%.

Results

Over a median (IQR) follow-up time of 5.9 (3.4, 8.9) years, there were 168 deaths. After adjustment, higher HDL composition of ceramide 24:2, glucosylceramide 16:0, and sphingomyelin 16:0 were significantly associated with death (HR per standard deviation greater lipid concentration, 95% CI; 1.31, 1.14-1.51; 1.25, 1.08-1.46; and 1.22, 1.07-1.40; respectively) (Figure).

Conclusion

After adjustment, higher HDL concentrations of ceramide 24:2, glucosylceramide 16:0, and sphingomyelin 16:0 were significantly associated with risk of death in patients with CKD. Further studies investigating functional significance for these findings may direct development of future therapies.

Funding

  • NIDDK Support