[Acute rejection in cadaveric renal transplantation under cyclosporine based therapy. Analysis of the risk factors and its influence on chronic dysfunction]

Abstract

Objectives: The aim of this study was to study the incidence and causes of acute rejection (AR) on cadaveric renal transplants under cyclosporine A-based immunosuppression, and to investigate the AR effect on the ocurrence of chronic dysfunction (CD) and on the outcome of transplantation.

Methods: We analyzed 794 renal transplants from cadaver donor between December, 1985 and December, 1999. We examined the major donor, recipient and graft-related factors and their influence in graft outcome. The diagnosis of AR was in 65% based in clinical and laboratorial findings: fever, decrease of diuresis, graft pain and/or strained and a serum creatinine increase of at least 0,4 mg/dl, and in 35% the diagnosis of AR was biopsy-proven. Statistics included univariate and multivariate analysis. Graft and patient survival rates were calculated by Kaplan-Meier method (with log-rank test).

Results: In the 794 renal transplants included in the study, 498 (63%) didn't have AR and 296 (37%) had at least one episode of AR. This overall incidence of AR of 37% is decreasing and in the last two years, 1998 and 1999 remained in 24% and 25%, respectively. The AR was associated with cadaver donor-related factors [ non traumatic cause of death (p=0,018), perfusion with Eurocollins solution (p=0,008) and cold ischemia time > 24 hours (p= 0,032)] and with recipient-related factors [age < 45 years (p=0,000) and immunosuppression with antithymocyte globulin (ATG) + azathioprine (Aza) + prednisone (Pred) + cyclosporine A (CsA) (p=0,006)]. Concerning graft-related factors acute tubular necrosis (ATN) was related with higher incidence of AR (35% of AR without ATN versus 48% of AR with ATN, p= 0,008) and this, was responsible by a significative increase of chronic dysfunction (CD) (p= 0,000) and by the worst graft function at the end of the first year (p= 0,000). Our results also showed that CD as a cause of graft loss increased substantially (23% vs 49%) in the presence of AR. The 1, 3, 5, 10 and 15-year graft survival in the patients with AR were, 94%, 85%, 74%, 50% and 38%, respectively, and in the patients without AR, 97%, 91%, 87%, 77% and 67%, respectively. These results were statistically significant ( p= 0,000). The AR didn't influence patient survival (p= 0,814).

Conclusions: Our overall incidence of AR (37%) is decreasing reaching in the last year 25%. The AR incidence increased significantly with grafts from cadaver donors with non-traumatic cause of death, preserved with Eurocollins solution, with cold ischemia times > 24 hours and in recipients with age < 45 years and with ATG+Aza+Pred+CsA immunosuppression regimen. ATN increased the AR incidence and this was associated with a higher ocurrence of CD and a worst graft function at 1 year. The graft lost by CD duplicate in the patients with AR. Graft survival was significantly worse in the patients with AR. The AR did not adversely affect patient survival.