LONG-TERM EFFICACY AND SAFETY OF CYCLOSPORINE IN RENAL-TRANSPLANT RECIPIENTS

Background and Methods. The safety of long-term immunosuppression with cyclosporine in renal-transplant recipients is not well understood. T his drug may cause a progressive toxic nephropathy, but it also preser ves renal function because it prevents rejection. To determine the eff ect of cyclosporine on renal function and graft rejection, we conducte d a retrospective analysis of data on 1663 renal-transplant recipients at six centers. Results. The rate of graft survival was 78 percent (m edian follow-up, 36 months). Grafts were lost in 279 patients (17 perc ent), mostly because of acute rejection (68 patients) or chronic graft dysfunction that was unresponsive to a reduction in the dose of cyclo sporine (125 patients); 92 patients died with functioning grafts. The median change in the serum creatinine concentration in all patients af ter transplantation was less than 0.001 mg per deciliter per month (<0 .09 mu mol per liter per month). Patients who had episodes of rejectio n had decreased rates of long-term graft function and survival. Eight percent of patients with functioning grafts at one year had first epis odes of rejection more than one year after transplantation. These late first rejections were associated with noncompliance with therapy (in 34 percent), blood cyclosporine concentrations that were marginally lo wer than those of patients who had no episodes of rejection, and a low rate of successful reversal of rejection (77 percent, vs. 97 percent in patients with rejection during the first year; P<0.001).Conclusions . The majority of renal-transplant patients tolerate long-term cyclosp orine therapy without evidence of progressive toxic nephropathy. Graft failure is most often due to rejection.