Gentamicin nephrotoxicity in the rat: influence of age and diabetes mellitus

1. This work examines the influence of age on some nephrotoxic signs of gentamicin in normal and diabetic rats (aged 1 and 24 months). 2. Gentamicin (80 mg-1 kg-1 day for 6 days, intramuscularly) produced the typical pattern of nephrotoxicity; significantly increasing the plasma concentrations of creatinine and urea, and the urinary excretion of protein, copper and zinc and significantly reducing creatinine clearance and cortical alkaline phosphatase activity. The antibiotic produced a marked damage in the proximal renal tubules. Nearly all of these effects were more marked in the old than in the young rats. Cortical gentamicin concentration in the young was about 67% of that in the old. 3. Streptozotocin-induced diabetes significantly ameliorated the signs of nephrotoxicity of gentamicin in young rats. In old rats, diabetes had significantly less protective effect on the gentamicin-induced nephrotoxic signs than in the young rats. Gentamicin nephrotoxicity in diabetic old rats induced mortality in about a third of the animals used, whereas no mortality was seen in young diabetic rats treated with gentamicin.