Nephrotoxicity of cis-diamminedichloroplatinum (II) (cis-platinum) and the additive effect of antibiotics: Morphological and functional observation in rats

Basic morphological and functional patterns of cis-platinum nephrotoxicity and the additive effect of combined antibiotics were investigated in male Wistar rats. Nephrotoxicity by cis-platinum is produced in a dose-related fashion and characterized by tubular damage primarily involving the corticomedullary junction. Partial recovery of renal function accompanied by diuresis occurs in 2–3 weeks, however, glomerular filtration rate (GFR) remains at low levels. Histologically, patchy areas of cystic changes remains in the inner cortex, among the areas of relatively normal nephrons. Concomitant use of antibiotics such as aminobenzyl penicillin, sulbenicillin, and cephalothin had no additive effect on platinum nephrotoxicity, from morphological and functional aspects. However, a combination of tobramycin and cis-platinum induced severe renal damage with most animals showing a continuous elevation of blood urea nitrogen and decrease in body weight before death. Histologically, acute tubular necrosis involving both inner and outer cortices was evident. Although cis-platinum is clinically used under enhanced diuresis, GFR and tubular damage have to be carefully monitored throughout the course of cis-platinum treatment. When nephrotoxic antibiotics are being concomitantly prescribed for patients already ingesting cis-platinum, then special precautions should be taken.