Impact of improving immunosuppressive treatment on outcome in cadaveric kidney transplantation

Background. Since the advent of cyclosporine-based immunosuppression for cadaveric kidney transplants in 1983, several changes have been made in immunosuppressive management at the University of Wisconsin. Since 1986, OKT3 has been available to treat steroid-resistant rejection; since 1992, OKT3 has been used as an induction agent replacing antilymphocyte globulin; and since 1993, mycophenolate mofetil has been used in 104 patients. Methods. The impact of different immunosuppressive strategies on overall and immunologic graft survival (defined as graft loss caused by rejection) was evaluated in 1210 primary cadaveric renal transplants at the University of Wisconsin. Covariables, including degree of human leukocyte antigen matching, age, gender, cause of kidney failure, and early graft dysfunction, were evaluated. The series was subdivided into four eras according to immunosuppressive regimen, and the results were analyzed by era. Results. Our principal findings are that immunologic graft survival has improved significantly during this series whereas overall graft survival has not. Mycophenolate was associated with a significant decrease in acute rejection. For a given patient, graft loss from rejection becomes less likely over time. Late rejection poses a greater risk than early rejection for graft loss. Conclusions. Improving outcomes may be related to improving immunosuppressive treatment,increasing degree of human leukocyte antigen matching, and better early graft function.