Circulating saturated fatty acids and incident chronic kidney disease: a meta-analysis of de-novo prospective cohort investigations

Background: Chronic kidney disease (CKD) is a global health problem which is associated with poor outcomes, and its prevalence is expected to increase. Identifying novel risk factors for CKD may lead to improved outcomes. Circulating saturated fatty acids (SFAs) have been posited as contributors to CKD risk. Objectives: We aimed to evaluate associations between circulating SFAs (measured in phospholipids in 7 cohorts, serum or plasma total in 5 cohorts, and cholesterol esters in 1 cohort) and incident CKD in 13 cohorts, and to pool results by meta-analysis across the studies. Methods: SFAs were measured in 13 cohorts in the Fatty Acids Outcomes Research Consortium, including 18,193 participants with estimated glomerular filtration rate >60 mL/min/1.73 m2 across 9 countries. Associations between each SFA [palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)] and incident CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 and ≥25% decrease from baseline) were assessed by Cox or Poisson regressions. Results were pooled using inverse variance weighted meta-analysis. Results: In total, 2554 participants developed CKD over a weighted median follow-up of 7.6 y. After adjustment, higher concentrations of 18:0 were associated with a lower risk of CKD with minimal heterogeneity (relative risk per interquintile range: 0.87; 95% confidence interval: 0.80, 0.95, P = 0.003, I2 = 14.7%). These associations remained consistent in secondary and sensitivity analyses. We did not observe significant associations of other SFAs with CKD. Conclusions: In a meta-analysis of 18,193 participants across 9 countries, we observed no indication that SFA increased CKD risk, whereas higher 18:0 concentrations were associated with a lower risk of CKD. Future research is needed to assess mechanisms by which SFA 18:0 may exert kidney-protective effects, and how circulating SFA 18:0 concentrations may be altered.