CYCLOSPORINE-INDUCED ACUTE RENAL DYSFUNCTION IN THE RAT EVIDENCE OF ARTERIOLAR VASOCONSTRICTION WITH PRESERVATION OF TUBULAR FUNCTION

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Abstract
Dose-related cyclosporine-induced renal dysfunction is the most frequent adverse effect noted with this exciting immunosuppressive drug. To investigate pathogenetic factors involved, we studied renal tubular function and afferent arteriolar morphology during severe experimental cyclosporine-induced reduction in glomerular filtration rate. Pair-fed male rats were given cyclosporine 50 mg/kg or olive oil vehicle alone by gavage for periods of 3–14 days. Glomerular filtration rate declined progressively, reaching a nadir of 0.18±.05 ml/min/100 g vs. .86±.03 ml/min/100 g in controls at 14 days (P P <0.05). We conclude that afferent arteriolar vasoconstriction rather than direct tubular injury is a major pathogenetic factor in experimental cyclosporine nephrotoxicity.