Circulating Sphingolipids and Incident CKD

Key Points Higher levels of sphingomyelin (SM) carrying fatty acid 16:0 were associated with a 69% increased risk of CKD. Higher levels of SM carrying fatty acid 24:0 were associated with 29% lower risk of rapid decline in kidney function and 33% higher eGFR. These findings support future efforts to explore pathways that explain how circulating SMs influence risk of kidney outcomes. Background Few studies have assessed whether ceramides (Cer) and sphingomyelin (SM) species are associated with kidney health in community-based studies. We investigated associations of eight Cer and SM species with incident CKD (eGFR <60 ml/min per 1.73 m 2 ) and other markers of kidney health ( i.e ., rapid decline in kidney function, eGFR, urine albumin-to-creatinine ratio) in a large cohort of American Indians. Methods We included participants from the Strong Heart Family Study, a prospective cohort study of risk factors for cardiometabolic diseases. We used generalized estimating equations to examine associations of Cer-16, Cer-20, Cer-22, Cer-24, SM-16, SM-20, SM-22, and SM-24, with kidney health. Results In total, 95 participants had CKD at baseline, 79 participants developed CKD during a mean follow-up of 5.4 years, 2167 participants remained free of CKD, and 270 participants experienced rapid decline in eGFR of >3 ml/min per 1.73 m 2 per year. After multivariable adjustment, higher levels of SM-16 were associated with greater risk of CKD (relative risk [RR], 1.69; 95% confidence interval [CI], 1.24 to 2.23), while higher levels of SM-24 were associated with lower risk of rapid decline in kidney function (RR, 0.71; 95% CI, 0.58 to 0.87). Higher levels of circulating SM-24 were also associated with higher eGFR (RR, 1.33; 95% CI, 0.47 to 2.18). Cer-16, Cer-20, Cer-22, Cer-24, and SM-20 were not associated with kidney health. Conclusions Associations of Cer and SMs with kidney health differ based on the length of the acylated saturated fatty acid attached to the SM.