Nephrotoxicity, in the form of transient
proteinuria,
azotemia, abnormalities of tubular function, and
acute renal failure, is the major toxic condition following administration of
streptozotocin. The renal morphologic and ultrastructural abnormalities associated with
streptozotocin remain poorly defined. We describe a patient with metastatic
islet cell tumor of the pancreas who was treated with 16 weekly courses of 1 g/m2 of
streptozotocin without marked change in renal function. Following a six-week hiatus without change in renal function, a single course of 1 g/m2 of
streptozotocin was administered and resulted in
acute renal failure. Light microscopic examination of the kidneys showed irregularly dilated renal tubules lined by low cuboid epithelium. The cells were pleomorphic and showed some mitoses. Nuclei were irregular and variably hyperchromatic. Electron microscopic examination disclosed large aggregates of fine microfilaments in the proximal convoluted tubules and collecting ducts. Microfilament aggregates were both free in the cytoplasm and membrane bound. Microfilaments were proved to be tonofilaments by the demonstration of
keratin within the epithelium, using the immunoperoxidase method. These data suggest that squamous
metaplasia may be an important part of
streptozotocin renal toxicity, and the suggestion is made that they may be an antecedent of neoplastic change.