Comparison of methods for prediction of nephrotoxicity during development.

Abstract

Drugs with nephrotoxic potential are continuously introduced into perinatal and pediatric medicine, and assessment of their relative toxicity is important. We compared different methods of assessment of renal damage during development in an attempt to establish their relative sensitivity, age and dose dependence. Newborn, 6- to 8-day-old and adult rats were treated for 7 days with intramuscular gentamicin (5, 10 or 20 mg/kg/day) or amikacin (5, 20 or 40 mg/kg/day). Renal damage was assessed by serum and urine creatinine, urine N-acetyl beta-glucosaminidase and beta 2-microglobulin, cortical sphingomyelinase in vivo and in vitro and morphologic changes in light and electron microscopy. As expected, there was a dose-dependent damage, with gentamicin being more nephrotoxic than amikacin, and with newborn rats more resistant. The light- and electron-microscopic assessment were more sensitive than all other methods, followed by urinary N-acetyl glucosaminidase and then by beta 2-microglobulin. Sphingomyelinase changes occurred only at the highest doses of gentamicin.