Roles of hemodynamic and tubular factors in gentamicin-mediated nephropathy

Gentamicin (GM) often causes polyuric acute renal failure (ARF) in humans and animals. GM-mediated ARF in rats was accompanied with activated renin-angiotensin system, increased renal endothelin content, and enhanced lipid peroxidation. Suppression of the renin-angiotensin activity by desoxycorticosterone acetate and saline drinking, and treatment with superoxide dismutase attenuated the GM-induced decline in whole-kidney GFR with well-maintained RBF but did not reduce the severity of tubular necrosis. On the other hand, treatment with dimethylthiourea, a hydroxyl radical scavenger, attenuated the GM-mediated decline in GFR and lessened tubular necrosis but did not ameliorate the reduction in RBF. These data suggest contributions of both vascular and tubular factors to the GM-induced decline in GFR in rats. However, relative importance of these factors probably differs with different doses of the agent.