CHRONIC IMMUNOSUPPRESSION OF THE RENAL-TRANSPLANT PATIENT

The advent of potent immunosuppressive drugs to prevent rejection has led to a phenomenal improvement in renal transplant results increasing spectacularly the number of transplant recipients to arrive in the tr ansplant clinic who remain for many years. This has engendered a serie s of questions about the most appropriate cyclosporine dosing for thes e patients that prevents rejection while avoiding toxicity. Three sepa rate issues were analyzed: the most appropriate combination strategy w ith cyclosporine as a base ''double'' or ''triple'' therapy; the possi bility of conversion from regimens containing cyclosporine to those de void of it; and the optimal cyclosporine dose for a maintenance regime n. A meta-analysis of seven individual prospective and randomized tria ls of double versus triple therapy encompassing 1,080 patients reveale d no statistical difference between the two regimens in terms of graft survival at 1 or 5 yr, patient survival, the rejection rate per patie nt, or the infection rate. In an analysis of 17 separate studies in wh ich conversion away from cyclosporine was attempted, in 629 individual s with 702 individuals left on cyclosporine as controls, a significant risk of acute rejection (P < 0.001) was found in the withdrawn group without evidence of improved graft survival. Certain factors such as p revious rejection, race, and degree of reactivity predicted even more rejection in the withdrawn group. Analyzing six separate studies of re nal transplant recipients maintained on cyclosporine for up to 5 yr wi th renal functional stability, one can conclude that a dose of approxi mately 4.0 mg/kg per day is optimal. Because of variant pharmacokineti cs or concomitant medicines, blood levels can confirm a therapeutic co ncentration with this target dose. In summary, a meta-analysis of mult iple studies reveals no benefit of triple therapy over prednisone/cycl osporine; no advantage to cyclosporine withdrawal, with the penalty of one third of the cases exhibiting rejection; and an optimal dose of c yclosporine for chronic immunosuppression of 4.0 mg/kg per day.