Circulating Very Long-Chain Saturated Fatty Acids and Incident CKD: A Meta-Analysis of Prospective Cohort Studies

Background: Chronic kidney disease (CKD) is a global health problem whose prevalence is expected to increase. Identification of novel risk factors for CKD may lead to improved outcomes. Saturated fatty acids (SFAs) have been posited as contributors to CKD risk. We performed a meta-analysis of de-novo analyses which were undertaken in 12 contributing cohorts using a harmonized protocol to evaluate the associations of SFA with incident CKD. Methods: SFAs were measured in 12 cohorts in the Fatty Acids Outcomes Research Consortium (FORCE), yielding a sample size of 17,838 participants with eGFR >60 mL/min/1.73 m2 across 9 countries. Associations between each SFA (16:0, 18:0, 20:0, 22:0, and 24:0) and incident CKD (defined as an eGFR <60 mL/min/1.73 m2 and ≥25% decrease from baseline) were assessed by Cox or Poisson regressions, adjusted for multiple potential covariates. Results were pooled using inverse variance weighted meta-analysis. Results: In total, 2,548 participants across the 12 cohorts developed CKD during follow-up. After adjustment for multiple covariates, higher concentrations of SFA 18:0 were associated with significantly decreased risk of incident CKD (RR per interquintile range of SFA 18:0 0.86, 95% CI 0.78 to 0.95, P=0.003, I2=0.00%) (Figure). SFA 18:0 was associated with slower annual decline in eGFR and less risk for ≥40% decline in eGFR from baseline in sensitivity analyses. Conclusion: In this meta-analysis of harmonized de-novo analyses among 12 cohorts across 9 countries (including 17,838 participants without baseline CKD), higher circulating levels of SFA 18:0 were consistently associated with decreased risk for incident CKD. Future work may be indicated to assess mechanisms by which SFA 18:0 may exert kidney-protective effects, and how circulating SFA 18:0 levels may be altered. Funding: Other NIH Support - NCATS KL2TR002317