Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations

Light microscopy, transmission electron microscopy and scanning electron microscopy were used to characterize the morphologic alterations and to localize the site of injury within the kidney 1, 2, 3, 5 and 7 days after the intraperitoneal injection of cis-diamminedichloroplatinum. Pathologic alterations were evident 3 days after the injection of the drug and were localized to the S3 segment of the proximal tubule situated in the outer stripe of the outer medulla. A spectrum of changes was seen in this S3 segment which included a thinning or focal loss of brush border, cellular swelling, condensation of the nuclear chromatin and focal areas of necrosis. After 5 days, widespread tubular necrosis of the S3 segment in the outer stripe was the predominant finding. Necrotic tubular epithelial cells could be seen detaching from the basal lamina and being sloughed into the tubular lumen. Only a bare basal lamina remained in many areas. Regeneration of the S3 segment was seen after 7 days and was characterized by tubules with widely dilated lumens which were lined by many low-lying epithelial cells. The observation that cis-diamminedichloroplatinum exerts its nephrotoxic effect on the S3 segment of the proximal tubule located in the outer stripe of the outer medulla demonstrates that the pattern of injury produced by this antitumor drug is similar to that associated with other nephrotoxic and ischemic models of acute renal failure.