Renal damage in mice after combined treatment with cisplatin and x-rays

Cisplatin is currently one of the most promising new drugs available for the treatment of testicular and ovarian cancer. Nephrotoxicxity can however be a dose limiting complication. The authors investigated the extent of renal damage, produced by cisplatin alone or in combination with X-rays, in order to predict late damage which might be expected in the clinic. Single doses of cisplatin stimulated tubular damage (assessed from the increased output of urine) within 3 days of injection. The urine output was increased by up to a factor of 2.5 at 1 to 2 weeks but returned to control levels within 6 to 8 weeks after low drug doses. After doses of cisplatin in excess of 6 mg/Kg, output remained elevated for at least 8 months. Glomerular function (assessed from clearance of /sup 51/CrEDTA) was also impaired after these high drug doses for up to 8 months. Single drug doses were given 1 to 4 weeks before irradiation. Damage was enhanced in all animals which had received the combined treatment, with enhancement ratios of 1.3 to 1.6 at 20 weeks after irradiation