Metabolic and Lipidomic Assessment of Kidney Cells Exposed to Nephrotoxic Vancomycin Dosages

Area of Science:

• Biochemistry
• Pharmacology
• Toxicology

Background:

• Vancomycin is crucial for treating infections caused by Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA).
• Adverse drug reactions to vancomycin include cytopenia, ototoxicity, and nephrotoxicity, with the latter's mechanism being poorly understood.
• Recent findings indicate that vancomycin concentrations in patient kidneys significantly exceed plasma levels during treatment.

Purpose of the Study:

• To investigate the metabolic and lipidomic effects of clinically relevant vancomycin concentrations on renal epithelial cells.
• To provide a dataset for researchers studying vancomycin-induced nephrotoxicity.
• To contribute to understanding the underlying mechanisms of vancomycin nephrotoxicity.

Main Methods:

• Utilized murine and canine renal epithelial cell lines.
• Applied untargeted and targeted gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analyses.
• Assessed endometabolic and lipidomic alterations.

Main Results:

• Both cell lines exhibited increased anabolic glucose reactions, leading to elevated sorbitol and lactate levels.
• Significant differences were observed in the lipidome profiles between the cell lines.
• This study presents the first endometabolic profiling of kidney cells exposed to clinically relevant vancomycin concentrations.

Conclusions:

• Clinically relevant vancomycin concentrations induce distinct metabolic and lipidomic changes in renal epithelial cells.
• The observed increase in glucose metabolism (sorbitol and lactate) may play a role in vancomycin nephrotoxicity.
• This research provides valuable data for elucidating the mechanisms of vancomycin-induced kidney injury.