Plasma metabolomics analysis in murine prerenal azotemia reveals changes in energy substrates, amino acid metabolism, and uremic toxins - Supplemental Figures and Tables
Résumé fourni par la source
Pre-renal azotemia (PRA) is a subtype of acute kidney injury (AKI) and represents 10-30% of all hospitalized cases of AKI. In contrast to AKI from acute tubular injury (ATI), PRA is commonly considered a benign condition, despite evidence that it is associated with adverse clinical outcomes. In this study, we used untargeted plasma metabolomics to study the potential systemic consequences of PRA as compared to ATI. We hypothesized that the PRA and ATI plasma metabolomes would share certain overlapping metabolite features, since both are marked by a decline in glomerular filtration rate (GFR) (the primary measure of kidney function), but that a unique PRA signature would be identified. Wildtype male C57BL/6 mice were utilized in established models of ischemic acute kidney injury (iAKI) or PRA induced by intraperitoneal furosemide followed by GFR restoration with normal saline resuscitation. Plasma from iAKI and PRA cohorts were analyzed by ultra-high performance liquid chromatography-mass spectrometry and 214 and 168 metabolites were detected, respectively. The PRA plasma metabolome was defined by 40 significantly changed metabolites, including 7 uremic toxins, with significant enrichment of tryptophan and fatty acid oxidation metabolites. When comparing models, the PRA and iAKI metabolomes overlap at the individual metabolite level (50% of PRA metabolome represented in iAKI metabolome) and share three significantly enriched pathways involved in energy substrate and amino acid metabolism. Further analysis identified three possible PRA plasma biomarkers - indolepyruvate, cystathionine, and kynurenine. Our results demonstrate that PRA causes systemic metabolic changes, some of which mirror changes in iAKI. Our results challenge the notion that PRA is inconsequential, and the metabolic pathways and uremic toxins identified herein warrant further study. The supplemental figures and tables uploaded here represent supporting data for the published manuscript.
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