Abstract: FR-PO1088
Eicosanoids and Related Metabolites Associated with ESKD in a Community-Based Cohort
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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