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Acute rejection and late renal transplant failure: risk factors and prognosis.

BACKGROUND
Acute rejection episodes are a major determinant of renal allograft survival, and the improvement of the transplantation results in the last two decades is largely due to a progressive decrease in the incidence of acute rejection. These results are explained by the incorporation of new immunosuppressive agents since the introduction of cyclosporine. Because the detrimental effect of acute rejection on graft survival is not limited to the early post-transplant period, we have focused on the impact of acute rejection episodes on late transplant failure in patients with the graft functioning 1 year after transplantation.


METHODS
We have retrospectively analysed in 3365 renal transplants performed in adults in Spain during 1990, 1994 and 1998 the incidence and severity of the acute rejection episodes, their risk factors, and their influence on graft and patient survival.


RESULTS
The incidence of rejection episodes in the whole series was 32.5%, decreasing in 1998 (25.1%) compared with the previous years (38%) (P<0.0001). Corticoid-resistant rejection episodes also decreased from 8% in 1990 and 1994 to 3.4% in 1998 (P<0.0001). Multivariate analysis showed that patients < 60 years old (P<0.0001), sensitized recipients (P = 0.038), patients with delayed graft function (P<0.0001), cytomegalovirus infection (P = 0.0060), and those transplanted in 1990 or 1994 (P<0.0001) had an increased incidence of rejection episodes. In the univariate analysis, induction treatment with antilymphocyte globulines or OKT3 (P = 0.0002), and traumatic donor death (P = 0.042) were associated with a lower incidence of acute rejection. In the univariate analysis of the transplants performed in 1998, addressed to evaluate the effect of the new immunosuppressive agents, treatment with mycophenolate mofetil (P<0.0001) or tacrolimus (P = 0.0067), but not with anti-IL2 antibodies reduced the incidence of acute rejection. Patients with rejection episodes had an increased risk of late graft failure (Cox proportional hazards model, P<0.0001), which was homogeneous in the three periods analysed, with no effect on patient survival (P = 0.13).


CONCLUSIONS
Despite a decreased incidence and severity of acute rejections in 1998, compared with the previous years, acute rejection still remains a powerful risk factor for late transplant failure.