Causes of late transplant failure in cyclosporine-treated kidney allograft recipients

Background: There is little information about very long-term outcomes of kidney allograft recipients exposed to calcineurin inhibitors. Methods: In this single-centre retrospective study with 20-year follow-up, we analyzed data from 644 patients who underwent primary renal transplantation between 1983 and 1993. Participants were treated with a cyclosporine-based immunosuppressive scheme and had allograft function at 1 year. Results: After 20 years, 15.2% patients died, 39.7% experienced allograft loss, 26.8% were alive with a functioning transplant, and 18.2% were lost to follow-up. Cardiovascular disease (30.8%), malignancy (26.6%) and infection (17.0%) were the main causes of death. Age, new-onset proteinuria > 1 g/day, major acute cardiovascular event (MACE), and malignancy were independent predictors of mortality at time-dependent multivariate analysis. Chronic rejection (63.3%), recurrent glomerulonephritis (14.0%), and nonspecific interstitial fibrosis/tubular atrophy (13.2%) were the leading cause of allograft loss. Basal disease, hepatitis C, difference between 1 year and nadir serum creatinine, new-onset proteinuria > 1 g/day, and MACE were independent predictors of transplant failure. Among patients with 20-year allograft function, we recorded the following complications: hypertension (85%), malignancy (13%), diabetes (9%), and cardiovascular disease (9%). Median serum creatinine and proteinuria were 1.4 mg/dL and 0.6 g/day, respectively. Conclusions: Prolonged use of cyclosporine may expose to several dose-related adverse events and may contribute to the development of allograft dysfunction but it does not necessarily cause relentless, progressive transplant failure if patients are carefully and consistently monitored during the follow-up.