Oxidative stress increases 1-deoxysphingolipid levels in chronic kidney disease

Abstract

Chronic kidney disease (CKD) leads to deep changes in lipid metabolism and obvious dyslipidemia. The dysregulation of lipid metabolism in turn results in CKD progression and the complications of cardiovascular diseases. To obtain a profound insight into the associated dyslipidemia in CKD, we performed lipidomic analysis to measure lipid metabolites in the serum from a rat 5/6 nephrectomy (5/6 Nx) model of CKD as well as in the serum from CKD patients. HK-2 cells were also used to examine oxidative stress-induced sphingolipid changes. Totally 182 lipid species were identified in 5/6 Nx rats. We found glycerolipids, total free fatty acids, and sphingolipids levels were significantly upregulated in 5/6 Nx rats. The atypical sphingolipids, 1-deoxysphingolipids, were significantly altered in both CKD animals and human CKD patients. The levels of 1-deoxysphingolipids directly relevant to the level of oxidative stress in vivo and in vitro. These results demonstrate that 1-deoxysphingolipid levels are increased in CKD and this increase directly correlates with increased kidney oxidative stress.