Nephrotoxicity of Aminoglycosides in Young and Adult Rats

Abstract

The nephrotoxicity of gentamicin and amikacin was evaluated comparatively in young and adult rats. The aminoglycosides were administered once daily for 14 days, gentamicin in a dose of either 20 or 60 mg/kg, and amikacin in a dose of either 60 or 180 mg/kg. Renal function was measured during and after treatment. In adult rats there was a dose dependent fall in the glomerular filtration rate which was preceded by histopathological changes in the proximal tubules. The nephrotoxicity of gentamicin was more severe than that of amikacin. The nephrotoxicity of either aminoglycoside was less severe in young rats than in adult rats. In the proximal tubules there were less histopathological changes in young rats than in the adult rats. The mechanism underlying this difference in nephrotoxicity was investigated by measuring the renal accumulation of gentamicin and amikacin. The renal uptake after the first dose of either aminoglycoside was similar in young and adult rats. Expressed as a percentage of the injected amount, the uptake decreased as the aminoglycoside dosage increased. The uptake of gentamicin was somewhat greater than that of amikacin. In young rats, the aminoglycoside concentration in total kidney as well as in renal cortex, was significantly less than in adult rats. This difference was due to the larger wet kidney weight relative to body weight in the young rats. The lower renal aminoglycoside levels in the young rats provide an explanation for the difference observed in aminoglycoside nephrotoxicity when comparing young and adult rats.