1. Lipid signatures of acute kidney injury to chronic kidney disease transition
- Author
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Ying-wen Chen, Wei-teng Wang, Lu-an Li, Qing-ying Shi, Jie-yi Luo, and Xin-ling Liang
- Subjects
lipidomics ,ultra-performance liquid chromatography-tandem mass spectrometry ,acute kidney injury ,chronic kidney disease ,glycerophospholipid ,Internal medicine ,RC31-1245 - Abstract
Objective To explore lipid signatures of renal tissue in acute kidney injury (AKI) and AKI-to-CKD transition by untargeted lipidomics. Methods Ischemia-reperfusion injury (IRI) mice were subjected to bilateral renal pedicle clamping for 30 min. A murine model was established for longitudinally examining CKD progression after AKI and analyzing renal lipid metabolites by ultra-high performance liquid chromatography-tandem mass spectrometry. Results The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were significantly elevated after IRI and acute tubular injury score rose obviously at Day 2 post-IRI. The levels of Scr and BUN declined at Day 14/28 post-IRI and yet failed to completely return to baseline with severe renal interstitial fibrosis. A total of 1715 lipid metabolites were identified. Marked differences existed in renal lipid metabolic profiles between IRI and sham-operated mice at the corresponding timepoint. And there were also distinct lipids characteristic among IRI groups. In AKI stage, renal neutral lipid accumulation was most pronounced. In AKI-to-CKD transition stage, the most distinguished features of lipid profile were changes of glycerophospholipids and Sphingolipids. At Day 28 post-IRI, the number of decreased glycerophospholipid was more than increased glycerophospholipid. The most pronounced increase of alkenyl (vinyl) ether-phosphatidylethanolamine and the most pronounced decrease of phosphatidylglycerol occurred at Day 28 post-IRI. KEGG pathway enrichment also indicated glycerophospholipid metabolism was a predominant pathway during AKI-to-CKD transition. Conclusion Our study has revealed renal lipid signatures in the whole process of AKI to CKD transition. Glycerophospholipid, especially alkenyl(vinyl) ether-phosphatidylethanolamine and phosphatidylglycerol, might be an important lipid involved in AKI to CKD transition. It may facilitate the future study of pathogenesis and mechanism involved in AKI-to-CKD transition.
- Published
- 2024
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