Acute kidney injury (AKI) is one of the leading causes of in hospital morbidity and mortality, particularly in critically ill patients. Although our understanding of AKI at the molecular level remains limited due to its complex pathophysiology, recent advances in both quantitative and spatial mass spectrometric approaches offer new opportunities to assess the significance of renal metabolomic changes in AKI models. In this study, we evaluated lipid changes in early ischemia reperfusion (IR) related AKI in mice by using SWATH mass spectrometry (MS) lipidomics. We found a significant increase in two abundant ether-linked phospholipids following IR at 6 hours post injury, a plasmanyl choline, phosphatidylcholine (PC) O-38:1 (O-18:0, 20:1) and a plasmalogen, phosphatidylethanolamine (PE) O-42:3 (O-20:1, 22:2). Both these lipids correlated with severity of AKI as measured by plasma creatinine. In addition to many more renal lipid changes associated with more severe AKI, PC O-38:1 elevations were maintained at 24 hours post-IR, while renal PE O-42:3 levels decreased, as were all ether PEs detected by SWATH-MS at this later time-point. To further assess the significance of this early increase in PC O-38:1, we used matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to determine that it occurred in proximal tubules, a region of the kidney that is most prone to IR injury and also rich in the rate-limiting enzymes involved in ether-linked phospholipid biosynthesis. Use of SWATH MS lipidomics in conjunction with MALDI-IMS for lipid localization will help in elucidating the role of lipids in the pathobiology of AKI.
- Acute Kidney Injury
- Ischemia-reperfusion injury
- Imaging Mass Spectrometry
- Copyright © 2016, American Journal of Physiology - Renal Physiology