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Nephrol Dial Transplant (1993) 8: 206-212
© 1993 European Renal Association-European Dialysis and Transplant Association

research-article

Chronic cisplatin nephropathy in rats

G. Brillet1, G. Deray1,, M. Dubois3, H. Beaufils5, P. Maksud2, R. Bourbouze4, C. Jouanneau5 and C. Jacobs1

1Department of Nephrology, Hôpital Pitie Paris, France 2Department of Nuclear Medicine, Hôpital Pitie Paris, France 3Inserm Ecole de chirurgie, UER dc Biologie humaine et expérimentale, Université René Descartes Paris, France 4Laboratoire de chimie biologique, UER dc Biologie humaine et expérimentale, Université René Descartes Paris, France 5Inserm U192, Hôpital Enfants Malades Paris, France

Correspondence and offprint requests to: Correspondence and offprint requests to: G. Deray, Service de Néphrologie, Hôpital de la Pitie-Salpetriere, 83, boulevard de l'Hôpital, 75013 Paris, France

The long-term renal effects of cisplatin have been very poorly studied. Therefore we investigated the chronic renal effects of various doses of cisplatin in three groups of male Sprague-Dawley rats. Group I received two injections of 5 mg/kg body weight (bw) at 4-week intervals, group II four injections of 2.5 mg/kg bw at 4-weeks intervals, and group III one injection of 5 mg/kg bw and four injections of 2.5 mg/kg bw at 4-weeks intervals. Controls received an equivalent amount of isotonic saline. Each group was evaluated 1, 3, or 6 months after the last injection of cisplatin.

One, 3 and 6 months after the last injection, cisplatin induced a marked decrease in glomerular filtration rate (GFR) evaluated as clearance of [99mTc]DTPA and creatinine clearance in all treated rats. Urinary NAG excretion remained unaltered. At 3 months post-cisplatin treatment GFR was significantly less (P<0.05) in group III (0.18±0.02 ml/min/100 g bw) when compared with group I (0.23±0.02 ml/min/100 g bw) or II (0.23 ±0.04 ml/min/100 g bw). In group I GFR was similar 1 month (0.24±0.02), 3 months (0.23±0.02) and 6 months (0.23±0.03 ml/min/100 g bw) after cisplatin treatment.

Cisplatin induced atrophy and dilatation of tubules with mononuclear cell infiltration associated with cyst formation. The glomerular and tubulointerstitial lesions were significantly enhanced in group III when compared with groups I and II.

This study indicates that repeated administration of cisplatin may induce a chronic tubulointerstitial nephropathy associated with a marked decrease in GFR, which is stable over time. The incidence and severity of chronic cisplatin toxicity is dose-related and is not modified by dividing the dose.

Keywords: cisplatin nephropathy; carcinoma; renal toxicity


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