The effect of diuretic pre-treatment on clinical, morphological and ultrastructural cis-platinum induced nephrotoxicity

The clinical, microscopical and ultrastructural effects of cis-platinum induced nephrotoxicity and the effects of pre-treatment with mannitol, furosemide (Lasix) or both diuretics in male Holtzman rats is described. Cis-platinum administered intraperitoneally at doses ranging from 2.5-7.5 mg/kg was associated with dose-dependent BUN and creatinine elevation; however, weight loss, which averaged 13%, was not dose dependent. Mannitol (4 g/kg) administered immediately prior to cis-platinum, or furosemide (2 or 12.5 mg/kg) administered either concomitantly or 30 minutes prior to cis-platinum, had no effect on BUN or creatinine elevations. Varying the route or time of furosemide administration did not alter the severity of nephrotoxicity but higher doses of furosemide were associated with more severe BUN elevation. Light microscopy of renal tissue demonstrated that the principle lesion corresponding to cis-platinum injury consisted of coagulative necrosis of tubular epithelium at the corticomedullary transition zone. Glomeruli showed no observable injury. The electron microscopy confirmed the observations from light microscopy, showing injured proximal tubular cells, with loss of the characteristic nuclear electron density, segregated nucleoli and cytoplasmic degeneration. The basement membrane of the proximal tubule, the distal tubular cells and the glomeruli were perserved. Analogous to the nephrotoxicity of aminoglycoside antibiotics, diuretic treatment of animals receiving cis-platinum aggravates rather than ameliorates nephrotoxicity.