Emma Parrott
Drug-induced predisposition to acute renal failure (ARF) is a facet of nephrotoxicity hitherto mostly uncharacterized, quite underestimated, and impossible to diagnose, which potentially has a high human and socioeconomic impact. Our study has identified urinary GM2AP as the first of a new class of biomarkers of the enhanced risk of suffering an acute renal failure after a subnephrotoxic treatment with gentamicin. Gentamicin-predisposed animals with no sign of renal cancer develop ARF when exposed to a second potentially nephrotoxic drug, also given at subnephrotoxic doses that are harmless to non-predisposed individuals. Subnephrotoxic gentamicin did not alter renal GM2AP gene expression or protein levels, determined by RT-PCR and Western blot and immunostaining, respectively, nor was its serum level modified. Further experiments indicate that, likely, the origin of the increased level of GM2AP in the urine might be a defective tubular handling of this protein as a consequence of gentamicin action.
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