CYCLOSPORINE ARTERIOLOPATHY - EFFECTS OF DRUG-WITHDRAWAL

Renal arteriolopathy in chronic cyclosporine-induced nephrotoxicity is characterized by an eosinophilic granular transformation of vascular smooth muscle cells of afferent glomerular arterioles that is thought to eventually progress to necrosis of individual muscle cells and hyal inization of the vessel wall. Although the lesion is highly specific f or cyclosporine-induced injury in humans, it has been difficult to rep roduce in normotensive animals. To study the natural history of the cy closporine arteriolopathy, we conducted sequential studies in salt-dep leted Sprague-Dawley rats using cyclosporin A (15 mg/kg subcutaneously ) treatment for 35 days, 49 days, 35 days plus 14 or 56 days of drug w ashout, or placebo (olive oil). Cyclosporin A produced a progressive d ecrease in renal function that significantly improved after discontinu ation of the drug. The arteriolopathy, scored semiquantitatively, was present by day 35 and did not improve with cyclosporine withdrawal wit hin 2 weeks but did dramatically regress after 56 days. However, tubul ointerstitial changes did not regress with drug discontinuation and we re present despite improvement in renal function. We conclude that cyc losporine induced arteriolopathy may be reversible and associated with improving renal function. Thus, the morphological evidence of arterio lopathy is dissociable from the progressive tubulointerstitial scarrin g. (C) 1998 by the National Kidney Foundation, Inc.