Lipid signatures of acute kidney injury to chronic kidney disease transition

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.