Background: Even with the development of modern immunosuppression, an acute rejection episode is a major complication after renal transplantation. Acute rejection episodes have been used as clinical indicators for chronic allograft nephropathy and graft loss. We investigated the timing and frequency of acute rejection episodes in relation to long-term graft survival and chronic allograft nephropathy.

Methods: The Long Term Efficacy and Safety Surveillance study of transplant patients receiving cyclosporin (Neoral) included 1706 adult renal transplants (1995 to 2003) with a functioning graft for at least 1 year. The impact on death-censored long-term graft survival was evaluated for acute rejection episodes (single or multiple) within 3 months, at 3 to 6 months, at 6 to 12 months, or at over 1 year posttransplant. A stepwise binary logistic regression was employed to identify independent risk factors for the time to occurrence of an acute rejection episode.

Results: An acute rejection episode occurring within 3 months posttransplantation had no effect on either death-censored long-term graft failure (P=.2157) or chronic allograft nephropathy (P=.9331). However, an acute rejection episode occurring at 1 year or later posttransplantation was significantly associated with death censored long-term graft failure (P <.0001) and chronic allograft nephropathy (P <.0001). The numbers of HLA-DR mismatches and younger recipient ages were independent risk factors for early acute rejection.

Conclusion: Among patients whose graft survives at least 12 months, an early acute rejection episode within 3 months posttransplant was not associated with either death-censored long-term graft survival or chronic allograft nephropathy among adults treated with cyclosporin. However, an acute rejection episode occurring at 1 year or later posttransplantation showed a positive association with death-censored long-term graft survival or chronic allograft nephropathy. Lower numbers of HLA-DR mismatches sum to reduce the occurrence of acute rejection and the hospitalization time.