Abstract: TH-PO0253
Chain-Length-Specific Ceramide Remodeling in CKD and Its Hepatic Drivers
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Wang, Jiahui, Peking Union Medical College Hospital, Beijing, China
- Zheng, Ke, Peking Union Medical College Hospital, Beijing, China
- Li, Xuemei, Peking Union Medical College Hospital, Beijing, China
Background
Chronic kidney disease (CKD) markedly iincreases atherosclerotic cardio-cerebrovascular risk beyond total cholesterol or low-density lipoprotein cholesterol, suggesting nontraditional lipid dysregulation in vascular injury. Ceramides are linked to metabolic stress and vascular injury, with chain-length-dependent effects. In our prior hemodialysis cohort, reduced very-long-chain ceramides (VLC-Cer) and increased glycosphingolipids were associated with incident cardio-cerebrovascular events. We therefore used a 5/6 nephrectomy CKD model to characterize systemic ceramide remodeling and identify its upstream organ source.
Methods
CKD was induced by 5/6 nephrectomy, with sham-operated mice as controls. Renal injury was confirmed by serum creatinine, blood urea nitrogen, and 24-hour urinary protein. LC-MS/MS lipidomics profiled ceramide-centered sphingolipid pathways in blood, liver, and kidney, while multi-omics characterized related enzymatic alterations.
Results
CKD mice developed stable renal injury. Circulating lipidomics revealed reduced Cer22:0, and differential lipids were enriched in ceramides and glycosphingolipids. Total ceramide abundance was unchanged, but the chain-length profile shifted toward reduced VLC-Cer, enrichment of long-chain ceramides, prominent C22-Cer depletion, and an inverse association between VLC-Cer and renal dysfunction. Cross-organ lipidomics showed that hepatic remodeling closely paralleled the circulating pattern, with enhanced diversion toward glycosphingolipids, whereas renal alterations were more consistent with local injury. Multi-omics profiling identified hepatic downregulation of CerS2 and ELOVL1, two key regulators of VLC-Cer synthesis.
Conclusion
CKD exhibits chain-length-specific ceramide remodeling, marked by C22-Cer depletion, reduced VLC-Cer proportion, and increased C16/C22 ratio. The concordance between circulating and hepatic abnormalities suggests that the liver may drive systemic nontraditional lipid dysregulation in CKD.
Acknowledgment
The authors acknowledge the use of AI tools for language refinement.