Cyst formation in rat kidney induced by cis-platinum administration

The long-term pathologic effects of the antitumor drug, cis-diamminedichloroplatinum II (CP) on the structure of the rat kidney were investigated. Light microscopy and transmission and scanning electron microscopy were used to characterize the morphologic changes 2 weeks, 4 weeks, and 6 months after the intraperitoneal injection of CP to rats. At all time intervals examined, the S3 segment of the proximal tubule located in the outer stripe of the medulla showed the most consistent pattern of injury. Two weeks after CP, the proximal tubules located in the outer stripe region as well as in the medullary rays were widely dilated and lined by low-lying epithelial cells, many of which contained large atypical nuclei. Many tubules still showed evidence of necrosis, whereas other tubules appeared to be undergoing atrophic changes. After 4 weeks, proximal tubular dilation continued resulting in the formation of numerous microcysts in the region of the outer stripe. These changes appeared to progress, and after 6 months large cysts (mean diameter 2152 +/- 1241 micrometer) were identified which involved the entire outer stripe, with many of these cysts extending to the subcapsular cortex. The kidneys at this time period showed a pattern of chronic renal injury in the outer stripe, and this damage was now also observed in the cortex. In several animals, small foci of abnormal foam cells surrounded by a basal lamina could be identified. We conclude that CP has a pronounced long-term effect and causes cyst formation in the rat kidney.