Nitrendipine protects against aminoglycoside nephrotoxicity in the rat

Aminoglycoside nephrotoxicity is a common clinical problem among hospitalized patients despite close attention to pharmacokinetics and dosing schedules. The present study was designed to evaluate the potential protective effect of nitrendipine, a calcium channel blocker, on the natural history of gentamicin renal injury in the rat. Gentamicin was administered intramuscularly in a dose of 40 mg/kg/day for 12 days to adult Fischer rats. Nitrendipine was given by gavage on a b.i.d. schedule in a dose of 30 mg/kg/day or 10 mg/kg/day. Gentamicin alone caused a significant decrease in glomerular filtration rate (GFR) and renal plasma flow (RPF). Concurrent administration of nitrendipine did not influence RPF, but promoted a significant increase in GFR. Nitrendipine also prevented the increase in urinary excretion of N-acetyl-glucosaminidase and beta-glucosidase, enzymatic markers of renal tubular injury in the gentamicin-treated animals. Gentamicin-induced pathologic injury was significantly ameliorated by nitrendipine. Renal cortical gentamicin content was diminished, but not significantly, by nitrendipine. The exact mechanism of action of nitrendipine in aminoglycoside-induced renal injury remains unknown. These observations suggest a potential pharmacologic approach to preventing a common problem with substantial morbidity.