Cyclosporine nephrotoxicity--experimental models

Cyclosporine A (CsA) represents one of the more important therapeutic advances in the field of kidney transplantation. However, its effectiveness is limited by serious side effects, most notably nephrotoxicity. Investigation of the mechanisms of CsA-induced renal dysfunction has been hampered by the lack of a suitable experimental model. The majority of studies using the rodent have failed to exhibit all of the structural changes seen in chronic CsA-induced nephrotoxicity reported in man, using pharmacologic doses administered orally, subcutaneously, or intravenously. More recently, studies using the rabbit as an experimental model have demonstrated leucocyte infiltration, tubular atrophy, interstitial fibrosis, and arteriolopathy after therapeutic doses of CsA over 30 days. These changes are similar to those seen in chronic CsA-induced nephrotoxicity in man.