Plasma Ceramides and CKD Progression in Type 2 Diabetes

Background: The Cardiovascular Event Risk Test (CERT) 1 score is used in general population to predict atherosclerotic CV events; however, whether altered plasma ceramides (CER) and CERT1 scores predict the progression of CKD is unknown. Methods: We measured plasma CER with targeted lipidomics in year 1 visit samples of 1054 Chronic Renal Insufficiency Cohort (CRIC) participants with T2D. Based on plasma CER 16:0, 18:0, 24:1 and their ratios to 24:0, CERT1 scores were calculated (2 points for concentrations/ratios in the 4th quartile and 1 point for concentrations/ratios in the 3rd quartile of reference population). In separate multivariate Cox regression models, we related CERT1 scores (Model 1) and individual CER and their ratios (Model 2) with a composite kidney outcome defined as a 50% decline in eGFR or the onset of ESKD. Results: Baseline mean age was 61 ± 9 years and eGFR 46 ± 13, respectively. 57% were male, 49% were Black, CERT1 score median (IQR) was 4 (2,7). There were 377 kidney events/6127 years of follow-up. CERT1 score was associated with higher risk of kidney events. In a separate Cox model of its components, CER 18:0, CER 24:1 and the ratios were associated higher risk of kidney events (Figure 1). However, with further adjustment for baseline eGFR and UACR, only CER ratio 24:1/24:0 associated with the kidney outcome (Figure 2). Conclusion: CER ratio 24:1/24:0 but not CERT1 score predicted CKD progression, independent of baseline eGFR and UACR. Interventions targeting plasma CER, in particular CER ratio 24:1/24:0 might slow CKD progression in T2D. Funding: NIDDK Support