Clinical trials: where are we now?

Clinical trials in transplantation have focused on improving outcomes and minimizing side effects associated with renal transplantation. Although immunologic tolerance, which means complete freedom from immunosuppressive drugs and maintenance of excellent long-term graft function, has seldom been achieved, in rare cases, this has been accomplished. Most current clinical trials focus on minimization of steroid use and calcineurin inhibitor use as a step toward tolerance, sometimes termed prope tolerance. Alternatively, new immunosuppressive agents are studied to assess their efficacy in preventing graft rejection with the anticipation of lesser toxicity. This review is organized in a case presentation style with actual cases from the University of Wisconsin kidney transplant experience presented as illustrations of actual scenarios in clinical trials. Lessons learned from these particular patients are then summarized with reference to the literature associated with the case. Using this format, some of the important lessons learned from clinical trials are outlined and directions for future study are noted. Clinical trials have permitted a dramatic improvement in graft survival and lowering of infectious and malignant side effects over the past 30-40 years. Nevertheless, we remain far from achieving true tolerance in patients for a variety of reasons.