Urinary Metabolomics Study of Vancomycin-Associated Nephrotoxicity Based on UHPLC-QTOF-MS/MS

Drug-induced nephrotoxicity is widespread and seriously affects human health. Vancomycin is a classical glycopeptide antibiotic. Vancomycin is widely used for severe infections caused by Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), but its obvious nephrotoxicity affects the safety of its clinical application. But the etiology for vancomycin induced kidney injury is not well understood. The aim of this study was to explore the potential mechanism of vancomycin-induced nephrotoxicity in rats. In this study, vancomycin (200mg·kg⁻¹) was used to establish kidney injury models in rats, and a metabonomic approach was employed using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) for the delineation of metabolic alterations. As a result, 20, 29, and 56 biomarkers were identified in urine samples of the treatment group compared with the control model on D2, D4, and D7, respectively. Changes in the levels of these metabolites indicated that amino acid metabolism and energy metabolism were disturbed in rats with vancomycin associated nephrotoxicity, and 5 nephrotoxicity metabolites were selected after the receiver operating characteristic curve (ROC) analysis as sensitive indexes for evaluating nephrotoxicity at the early stage. Our results suggest that vancomycin has a damaging effect on rats via the interruption of multiple metabolic pathways primarily involving amino acid and energy metabolism.