To elucidate the role of the glomerular filtration barrier in the development of nephrotoxic acute renal failure, we produced acute renal failure in rats with either gentamicin or tobramycin. Both drugs evoked changes in the gomerular capillary endothelium. Gentamicin administration resulted in a dose-related decrease in the diameter, density and area of endothelial fenestrae, which was considerably more pronounced than those observed with tobramycin. Prolonged, high-dose gentamicin administration caused a decrease in creatinine clearance, an increase in plasma renin activity and a corresponding decrease in the area available for filtration. These changes reverted with continued drug administration. These results support the notion that morphological alterations in the filtration barrier are responsible for the decrease in filtration observed in acute renal failure. The changes may be at least in part mediated by the renin-angiotensin system.
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