Long term effect of cis-diamminedichloride platinum (CDDP) on renal function and structure in man

Abstract

To examine CDDP induced nephrotoxicity in patients with testicular carcinoma, we measured renal function prior to therapy and at six month intervals for twelve months in fifteen patients and twenty-four months in seven patients. CDDP was given iv at 20 mg/M2 per day for five days at three week intervals. Eight patients received three courses, four received four courses and three received more than four courses. The mean creatinine clearance +/- SD prior to treatment was 112 +/- 12 ml/min. By six months, it had decreased to 68.5 +/- ml/min (p less than 0.01) and it remained at that level. Plasma creatinine and blood urea nitrogen increased significantly. Subjects receiving other potential nephrotoxins in addition to CDDP developed a greater decrease in creatinine clearance (p less than 0.05). Proteinuria and functional tubular disturbances were not observed. Microscopic features were characterized by hydropic degeneration of the renal tubular epithelium, thickened tubular basement membranes and mild interstitial fibrosis. Electron microscopy revealed phagolysosomes filled with flocculent material. CDDP resulted in a permanant, nonspecific renal injury in our patients. Although the renal injury has remained subclinical, future courses of CDDP may lead to clinically important chronic renal failure.