Long-term consequences of cis-platinum-induced renal injury: a structural and functional study.

Previous studies have shown that a single dose of the antitumor drug, cis-platinum, causes renal cyst formation in rats 1-6 months after drug injection. This observation led to a further evaluation of the long-term effects of cis-platinum on the kidney of the rat. Fisher 344 rats (N = 13) were given either a single intraperitoneal injection of cis-platinum (6 mg/kg body weight) or saline (control) and 15 months later renal function and pathology were assessed. The glomerular filtration rate and urinary osmolality in the cis-platinum-treated rats at 15 months were significantly reduced compared to controls, 520 +/- 59 microliter/min/gm kidney weight versus 799 +/- 100 (P less than .05) and 871 +/- 194 mOsm/kg H2O versus 1471 +/- 162 (P less than .05), respectively. Renal injury was less marked and of a more chronic type than to that originally described 6 months after cis-platinum. Morphometric evaluation of renal injury revealed cis-platinum-treated rats had greater numbers of abnormal proximal tubules (atrophic or hyperplastic) when compared to control rats. Glomerular sclerosis and interstitial fibrosis were also more prevalent in the animals injected with cis-platinum. In the inner stripe of the outer medulla, numerous markedly dilated tubules filled with hyaline casts and lined by simple squamous cells were present. To assess why cis-platinum exerts a chronic effect on the kidney, total platinum levels were measured in different regions of the kidney as a function of time after drug injection. Platinum levels were significantly elevated in the cortex, outer and inner stripe regions, and in the inner medulla for as long as 1 month after cis-platinum treatment. By 2 months, however, the values were no greater than controls. In summary, cis-platinum exerts a significant long-term chronic effect on the structure and function of the rat kidney.