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Toxicologic Pathology
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Journal Article

Cyclosporine Nephrotoxicity

Bernhard Ryffel

Preclinical Research Sandoz Ltd., and Department of Pathology, Kantonsspital, CH-4002 Basel, Switzerland

Michael J. Mihatsch

Preclinical Research Sandoz Ltd., and Department of Pathology, Kantonsspital, CH-4002 Basel, Switzerland

Cyclosporine (CSA) is a new immunosuppressant which has selectivity for the immune system and is without systemic side effects at therapeutic doses. In contrast to the cytotoxic class of immunosuppressants, no myelotoxic, teratogenic, mutagenic, or carcinogenic effects were observed. Nevertheless, overdosage may lead to renal dysfunction, which occurs mainly in rats, and of ten complicates its clinical use. The experimental data also showed that significant nephrotoxicity was only caused under specific conditions at therapeutic doses. These conditions included ischemia, heminephrectomy, concomitant administration of nephrotoxic drugs, and/or genetic predisposition. Thus, concomitant renal damage is a prerequisite in order to obtain overt nephrotoxicity at therapeutic CSA doses. Since these conditions cannot be avoided in patients, nephrotoxicity of ten occurs at therapeutic doses in man (45). The rat might be a suitable experimental model of CSA nephropathy displaying similar morphologic and functional changes as observed in man. This model also allows further investigations on the pathogenic mechanisms which are elusive at the present time.

Toxicologic Pathology, Vol. 14, No. 1, 73-82 (1986)
DOI: 10.1177/019262338601400109
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