Elective Cyclosporine Withdrawal After Renal Transplantation: A Meta-analysis

Objective.—To determine whether it is safe to electively discontinue cyclosporine therapy after renal transplantation. Data Source.—MEDLINE and bibliographies from recent publications. Study Selection.—Controlled trials assessing the rate of acute rejection, graft loss, and mortality after elective cyclosporine withdrawal. Data Extraction.—We compared outcomes in patients who underwent withdrawal from cyclosporine treatment with patients who were not withdrawn (part 1), and in a separate analysis (part 2), with patients who never received cyclosporine. Data Synthesis.—In part 1 of the meta-analysis, consisting of 10 randomized and seven nonrandomized trials, there was a greater combined rate of acute rejection among patients in whom cyclosporine was withdrawn compared with control patients who continued to receive cyclosporine (weighted difference in episodes per patient, 126; 95% confidence interval [Cl], 0.085 to 0.167; P<.001). However, there were no differences in graft loss (weighted difference in grafts lost per patient per year, —0.009; 95% Cl, —0.022 to 0.004; P=0.19) or mortality (weighted difference in deaths per patient per year, —0.005; 95% Cl, —0.016 to 0.006; P=.40) attributable to cyclosporine withdrawal. In part 2 of the meta-analysis, consisting of three randomized and three nonrandomized trials, the combined rate of graft loss for patients who were withdrawn from cyclosporine was not significantly different vs control patients who never received cyclosporine (weighted difference in grafts lost per patient per year, —0.020; 95% Cl, —0.043 to 0.003; P=.08). However, when the three randomized trials were analyzed separately, graft survival was better in patients who were withdrawn from cyclosporine (weighted difference in grafts lost per patient per year, 0.0382; 95% Cl, 0.0002 to 0.0762; P=.049). None of the outcomes was affected by the timing or manner of the cyclosporine withdrawal. Conclusions.—The increased incidence of acute rejection following elective cyclosporine withdrawal does not affect short-term graft or patient survival after renal transplantation. Whether long-term consequences will outweigh the benefits of elective withdrawal remains to be determined.