Acute and chronic cisplatin nephropathy in rats

Cisplatin (cis-dichlorodiammineplatinum-II) is a new class of platinum coordination compounds showing a potent antitumor activity, but it also produces adverse effects on renal function. In this study, cisplatin nephropathy and renal accumulation of platinum were analyzed in rats after acute chronic treatment. A single intraperitoneal dose of cisplatin (6 mg. per kg.) induced marked focal necrosis in the proximal and distal tubules with a maximal lesion on day 7. The tubular damage was localized mainly in the corticomedullary region, where the concentration of platinum was the highest within the kidney. Repeated treatment with cisplatin (1 mg. per kg., intraperitoneally, twice weekly) for 11 weeks resulted in massive tubular basement membranes. Some glomeruli appeared fibrotic, indicating that chronic treatment with cisplatin could cause irreversible renal damage. The results indicated that the toxicity of platinum was probably a major factor for cisplatin nephropathy.