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Abstract: SA-PO0905

Association of Potential Renal Acid Load with Circulating Sphingolipids in Patients with Kidney Failure Treated with Maintenance Hemodialysis

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism

Authors

  • Tilander, Charles T., University of Washington, Seattle, Washington, United States
  • Kim, Hyunju, University of Washington, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Lidgard, Benjamin, University of Washington, Seattle, Washington, United States
Background

Patients treated with maintenance hemodialysis face increased mortality. Sphingolipids (SL) are a class of lipids that are associated with death in dialysis patients. Dietary acid intake, measured by Potential Renal Acid Load (PRAL), has been associated with mortality risk. Whether PRAL is associated with circulating SL in dialysis is unclear. We aimed to test the association of diet, via PRAL, with SL levels in dialysis patients.

Methods

We used data from the Hemodialysis study, a 2x2 factorial trial of dialysis dose and dialyzer flux, which included 48-hour dietary diaries for calculation of PRAL obtained before baseline serum collection. We measured 4 SL subclasses (ceramides and sphingomyelins with long-chain (14-18 C) and very-long chain (20+ C) fatty acids) in 926 participants using targeted tandem-mass spectrometry. Our outcome was fold-change in SL subclass levels per quartile of PRAL. We tested the associations of PRAL with SL via linear regression, controlling false discovery rate (<5%).

Results

The mean (SD) age was 56 (14) years; median (IQR) dialysis vintage was 1.92 (0.83, 4.08) years. Participants with PRAL in the highest vs. lowest quartiles were associated with 0.11-fold (95% CI 0.04, 0.17) higher circulating concentrations of long-chain ceramides, with each SD-higher PRAL associated with a 0.03 (95% CI 0.01, 0.05) fold greater long-chain ceramide concentration (Table).

Conclusion

In a dedicated study of patients with kidney failure treated with hemodialysis, higher PRAL was significantly associated with higher long-chain ceramide concentrations. Higher long-chain ceramide concentrations have been associated with risk of death in this population. Our findings show that diet may be a route to modify SL levels in this population.

Acknowledgment

This work was supported by NIH NCATS under award number KL2TR002317 (BL). Additional support was provided by P30 DK035816. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, NCATS, or NIDDK.

Association of dietary markers with sphingolipid subclasses, adjusted.
Dietary MarkerFold-change in SL Q2 vs Q1Fold-change in SL Q3 vs Q1Fold-change in SL Q4 vs Q1P for trendFold-change in SL per-SD increasep-value
Long-chain ceramides0.04 (-0.02, 0.09)0.07 (0.01, 0.13)0.11 (0.04, 0.17)0.0090.03 (0.01, 0.05)0.009
Long-chain sphingomyelins0.02 (-0.01, 0.06)0.05 (0.01, 0.09)0.05 (0.00, 0.09)0.140.02 (0.00, 0.03)0.20
Very-long ceramides0.03 (-0.03, 0.10)0.02 (-0.05, 0.09)0.03 (-0.04, 0.11)0.630.00 (-0.02, 0.02)0.87
Very-long sphingomyelins0.02 (-0.02, 0.06)0.01 (-0.03, 0.06)0.02 (-0.03, 0.07)0.630.01 (-0.01, 0.02)0.59

Funding

  • Other NIH Support