Chronic cyclosporin nephropathy: long-term effects of cyclosporin on renal allografts.

Cyclosporin (CSA) has significantly reduced both incidence and severity of acute rejection, and brought excellent graft survival rates. Chronic CSA nephrotoxicity seems to be the second most important diagnosis responsible for the late graft failure. CSA-associated arteriolopathy (CAA) is well known as a characteristic lesion of chronic CSA nephrotoxicity by graft biopsies. There are few reports on the long-term outcome of renal transplant patients with biopsy-proven chronic CSA nephrotoxicity after diagnosis of CAA. We conducted two studies, the long-term outcome of the patients with CAA, and the FGS lesion related to CAA. Seventy-four CAA patients continued on CSA therapy after diagnosis of CAA were classified into two groups by outcome of the graft after follow-up: the functioning graft group (n = 30) and the graft-loss group (n = 44). There was no significant difference in severity of CAA grade between the functioning and graft-loss groups. Concomitant lesion of chronic rejection but not severity of CAA was the most important risk factor of graft loss for CAA patients in our study. Of a total of 54 recipients with FGS lesion, 32 patients (59%) were diagnosed as CAA-associated glomerulopathy (CAG) accompanied with severe CAA. Eighteen of 32 CAG patients lost their grafts after follow-up. Their serum creatinine level at biopsy was higher than that of the functioning group; however, there was no significant difference in daily proteinuria at biopsy between two groups. We have tried to reduce CSA dosage to maintain lower blood levels than the usual optimal target levels, but did not discontinue CSA after diagnosis of severe CAA and FGS lesion. In 15 isolated pure CAG patients, those with increasing daily proteinuria exceeding 2 g lost their graft function even after reducing CSA administration. The change in daily proteinuria seems to be a useful indicator for late graft loss in the patients of FGS lesion with severe CAA. CAA is not specific for chronic CSA nephrotoxicity, and FGS lesion is also a non-specific lesion often developed in renal allografts. Our study revealed clinicopathological characteristics of chronic CSA nephrotoxicity. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. FGS lesion accompanied by CAA is considered as a new concept of CAG, and increasing proteinuria in patients with CAG is a good indicator for poor outcome. These results will contribute towards an appropriate therapeutic plan for renal transplant patients undergoing long-term CSA treatment.