LC-MS/MS-Based Serum Metabolomics and Transcriptome Analyses for the Mechanism of Augmented Renal Clearance

Augmented Renal Clearance (ARC) refers to the increased renal clearance of circulating solute in critically ill patients. In this study, the analytical research method of transcriptomics combined with metabolomics was used to study the pathogenesis of ARC at the transcriptional and metabolic levels. In transcriptomics, 534 samples from 5 datasets in the Gene Expression Omnibus database were analyzed and 834 differential genes associated with ARC were obtained. In metabolomics, we used Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry to determine the non-targeted metabolites of 102 samples after matching propensity scores, and obtained 45 differential metabolites associated with ARC. The results of the combined analysis showed that purine metabolism, arginine biosynthesis, and arachidonic acid metabolism were changed in patients with ARC. We speculate that the occurrence of ARC may be related to the alteration of renal blood perfusion by LTB4R, ARG1, ALOX5, arginine and prostaglandins E2 through inflammatory response, as well as the effects of CA4, PFKFB2, PFKFB3, PRKACB, NMDAR, glutamate and cAMP on renal capillary wall permeability.

Automated summary

Augmented Renal Clearance (ARC) refers to increased renal clearance of solute in critically ill patients. This study utilized transcriptomics and metabolomics analysis to investigate the pathogenesis of ARC at the transcriptional and metabolic levels. Transcriptomics analysis of 534 samples identified 834 differential genes associated with ARC, while metabolomics analysis of 102 samples revealed 45 differential metabolites related to ARC. Combined analysis showed changes in purine metabolism, arginine biosynthesis, and arachidonic acid metabolism in ARC patients. The occurrence of ARC may be attributed to alterations in renal blood perfusion and renal capillary wall permeability mediated by various genes and metabolites.