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Early lipid changes in acute kidney injury using SWATH lipidomics coupled with
MALDI tissue imaging
#MMPMID26911846
Rao S
; Walters KB
; Wilson L
; Chen B
; Bolisetty S
; Graves D
; Barnes S
; Agarwal A
; Kabarowski JH
Am J Physiol Renal Physiol
2016[May]; 310
(10
): F1136-47
PMID26911846
show ga
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
sequential window acquisition of all theoretical spectra (SWATH)-mass
spectrometry (MS) lipidomics. We found a significant increase in two abundant
ether-linked phospholipids following IR at 6 h postinjury, 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 of these lipids
correlated with the 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 h 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.
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