Circulating Sphingolipids and Incident CKD

Background: Few studies have assessed whether ceramides and sphingomyelin species are associated with kidney health in community-based studies. We investigated associations of 8 ceramide and sphingomyelin species with incident CKD (eGFR <60 mL/min/1.73 m 2 ) and other markers of kidney health (i.e., rapid decline in kidney function, estimated glomerular filtration rate (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 cardio-metabolic diseases. We used generalized estimating equations to examine associations of ceramide (Cer)-16, Cer-20, Cer-22, Cer-24, sphingomyelin (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, 2,167 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 (RR=1.69, 95% CI: 1.24-2.23), while higher levels of SM-24 were associated with lower risk of rapid decline in kidney function (RR, 95% CI: 0.71, 0.58-0.87). Higher levels of circulating SM-24 were also associated with higher eGFR (RR=1.33, 95% CI, 0.47, 2.18). Cer-16, Cer-20, Cer-22, Cer-24, and SM-20 were not associated with kidney health. Conclusions: Associations of ceramide and sphingomyelins with kidney health differ based on the length of the acylated saturated fatty acid attached to the sphingomyelin.