Linchuang shenzangbing zazhi (Jun 2024)
Lipid signatures of acute kidney injury to chronic kidney disease transition
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.
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