Sub-nephrotoxic doses of gentamicin predispose animals to developing acute kidney injury and to excrete ganglioside M2 activator protein

Kidney Int. 2010 Nov;78(10):1006-15. doi: 10.1038/ki.2010.267. Epub 2010 Aug 18.


We studied whether nephrotoxic drug administration sensitizes to acute renal failure (ARF) by administering a sub-nephrotoxic dose of gentamicin. This pre-treatment sensitized animals with no sign of renal injury to develop ARF when exposed to a second potential nephrotoxic drug, also given at sub-nephrotoxic doses that would be otherwise harmless to non-sensitized animals. We identified urinary ganglioside M2 activator protein (GM2AP) as a biomarker of an enhanced sensitivity to suffer ARF following sub-nephrotoxic treatment with gentamicin. Sub-nephrotoxic gentamicin did not alter renal GM2AP gene expression or protein levels, determined by reverse transcriptase-PCR, western blot, and immunostaining, nor was its serum level modified. The origin of increased GM2AP in the urine is thought to be a defective tubular handling of this protein as a consequence of gentamicin action. Hence, markers of acquired sensitivity may improve the prevention of ARF by enhancing our capacity to monitor for this condition, in a preemptive manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Gangliosides / metabolism*
  • Gentamicins / adverse effects*
  • Protein Synthesis Inhibitors / adverse effects
  • Rats
  • Rats, Wistar
  • Risk Factors


  • Biomarkers
  • Gangliosides
  • Gentamicins
  • Protein Synthesis Inhibitors