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Abstract: FR-PO1088

Eicosanoids and Related Metabolites Associated with ESKD in a Community-Based Cohort

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Surapaneni, Aditya L., New York University Department of Medicine, New York, New York, United States
  • Schlosser, Pascal, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Rhee, Eugene P., Mass General Brigham Inc, Boston, Massachusetts, United States
  • Cheng, Susan, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Coresh, Josef, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Grams, Morgan, New York University Department of Medicine, New York, New York, United States
Background

Eicosanoids are derivatives of polyunsaturated fatty acids and participate in the inflammatory response and endothelial function maintenance. Specific eicosanoids have been linked to various diseases, including hypertension and asthma, and may reduce renal blood flow. A systematic investigation of eicosanoid-related metabolites and adverse kidney outcomes could identify key mediators of kidney disease and inform work in drug development.

Methods

Profiling of eicosanoid-related metabolites was performed in 9,650 participants in the Atherosclerosis Risk in Communities Study (visit 2; mean age, 57 years). The associations between metabolite levels and the development of ESKD was investigated using Cox proportional hazards regression (N= 256 events; median follow-up, 25.5 years). Metabolites with statistically significant associations with ESKD were evaluated for a potential causal role using Mendelian randomization techniques, linking genetic instruments for eicosanoid levels to genome-wide association study summary statistics of estimated GFR.

Results

The 223 eicosanoid-related metabolites that passed QC were generally uncorrelated with eGFR in cross-sectional analyses (median Spearman correlation, -0.03; IQR -0.05 to 0.002). In models adjusted for multiple covariates, including baseline eGFR, three metabolites had statistically significant associations with ESKD (p-value <0.05/223). These included a hydroxyoctadecenoic acid, a dihydroxydocosapentaenoic acid which were protective and an arachidonic acid, detrimental. Mendelian randomization suggested a causal role for the hydroxyoctadecenoic acid in determining eGFR.

Conclusion

High throughput eicosanoid profiling can identify metabolites that may play a protective role in the development of kidney disease.

Funding

  • Other NIH Support