Chronic ciclosporin nephrotoxicity: a rabbit model

Ciclosporin (CsA) was administered intravenously for 30 days to New Zealand white rabbits at the following doses: group A, 2.5 mg/kg/day; group B, 5.0 mg/kg/day; group C, 10 mg/kg/day; group D, saline control; group E, vehicle (cremophor-EL) control. Creatinine clearance was significantly reduced (p less than 0.05) at time of sacrifice in group C as compared to controls. There were no apparent differences among the five groups with respect to body weight gain or blood pressure. Morphologically, there were marked changes in the cytoarchitecture of the kidneys from all groups of animals treated with CsA. At the light microscopic level, in contrast to controls, there was the presence of leukocyte infiltration, tubular atrophy, interstitial fibrosis, and arteriolopathy. At the ultrastructural level, numerous vacuoles, lysosomal-like structures, and loss of cellular integrity were seen in the proximal and distal tubules, as well as interstitial fibrosis in the form of numerous collagen fibers. No changes in the glomeruli were seen in any of the CsA-treated groups. These findings are consistent with chronic CsA nephrotoxicity similar to that seen in man.