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

Int J Mol Sci. 2021 Sep 18;22(18):10111. doi: 10.3390/ijms221810111.


Vancomycin is a glycopeptide antibiotic used against multi-drug resistant gram-positive bacteria such as Staphylococcus aureus (MRSA). Although invaluable against resistant bacteria, vancomycin harbors adverse drug reactions including cytopenia, ototoxicity, as well as nephrotoxicity. Since nephrotoxicity is a rarely occurring side effect, its mechanism is incompletely understood. Only recently, the actual clinically relevant concentration the in kidneys of patients receiving vancomycin was investigated and were found to exceed plasma concentrations by far. We applied these clinically relevant vancomycin concentrations to murine and canine renal epithelial cell lines and assessed metabolic and lipidomic alterations by untargeted and targeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses. Despite marked differences in the lipidome, both cell lines increased anabolic glucose reactions, resulting in higher sorbitol and lactate levels. To the best of our knowledge, this is the first endometabolic profiling of kidney cells exposed to clinically relevant vancomycin concentrations. The presented study will provide a valuable dataset to nephrotoxicity researchers and might add to unveiling the nephrotoxic mechanism of vancomycin.

Keywords: GC/MS; LC/MS; lipidomics; mass spectrometry; metabolomics; nephrotoxicity; tubule; vancomycin.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Chromatography, Liquid
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Gas Chromatography-Mass Spectrometry
  • Glutathione / metabolism
  • Kidney / drug effects*
  • Kidney Tubules, Collecting / metabolism
  • Lipidomics*
  • Lipids / chemistry
  • Madin Darby Canine Kidney Cells
  • Mass Spectrometry
  • Metabolomics
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Mice
  • Staphylococcal Infections / drug therapy
  • Vancomycin / pharmacology*


  • Anti-Bacterial Agents
  • Lipids
  • Vancomycin
  • Glutathione