A network meta-analysis of induction immunosuppression for simultaneous pancreas-kidney transplant from randomized clinical trials

Objectives: Induction immunosuppression for simul-taneous pancreas-kidney transplant has helped reduce graft loss due to early rejection. Both thymoglobulin and interleukin 2 receptor antagonists are the most commonly used induction agents; however, some high-volume centers prefer alem-tuzumab. This network meta-analysis aimed to compare different induction regimens for simultaneous pancreas-kidney transplant in terms of both pancreas and patient graft survival, as well to assess acute rejection.

Materials and Methods: A systematic review was conducted to identify randomized clinical trials up to October 31, 2019, that examined induction regimens for simultaneous pancreas-kidney transplant. Study characteristics, postoperative data (patient, pancreas, and kidney graft survival), complications (eg, bleeding), infection rates, and malignancy rates were extracted. We compared all regimens using random-effects network meta-analyses to maintain rando-mization within trials.

Results: This study identified 7 randomized clinical trials that involved 536 patients, which reported 5 induction regimens. These regimens included antithymocyte globulin (97 patients), alemtuzumab (42 patients), 2 doses (113 patients) or 5 doses (164 patients) of daclizumab, and no induction therapy (120 patients). In the network meta-analysis, a regimen with 2 doses of daclizumab was consistently ranked first for patient survival and kidney and pancreas graft survival. In contrast, alemtuzumab was ranked best for acute rejection (both pancreas and kidney). Rates of major infection (ie, cytomegalovirus) and malignancy were reported in 3 studies, precluding a reliable analysis.

Conclusions: Daclizumab with 2 doses, given before simultaneous pancreas-kidney transplant, was associated with the best rates of patient and graft survival. Despite the recent withdrawal of daclizumab, an alternative anti-interleukin 2 induction regimen (basiliximab) has demonstrated promising results in nonrandomized series, warranting that further high-quality large-scale randomized clinical trials are still needed.