The treatment of antibody-mediated rejection in kidney transplantation: An updated systematic review and meta-analysis

Background Current treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B cells, plasma cells, and the complement system have featured in recent studies of AMR. Methods We conducted a systematic review and meta-analysis of controlled trials in kidney transplant recipients using Medline, EMBASE, and CENTRAL from inception to February 2017. Results Of 14 380 citations, we identified 21 studies, including 10 randomized controlled trials, involving 751 participants. Since the last systematic review conducted in 2011, we found nine additional studies evaluating plasmapheresis + intravenous immunoglobulin (IVIG) (two), rituximab (two), bortezomib (two), C1 inhibitor (two), and eculizumab (one). Risk of bias was serious or unclear overall and evidence quality was low for the majority of treatment strategies. Sufficient RCTs for pooled analysis were available only for antibody removal, and here there was no significant difference between groups for graft survival (HR 0.76; 95% CI 0.35-1.63; P = 0.475). Studies showed important heterogeneity in treatments, definition of AMR, quality, and follow-up. Plasmapheresis and IVIG were used as standard-of-care in recent studies, and to this combination, rituximab seemed to add little or no benefit. Insufficient data are available to assess the efficacy of bortezomib and complement inhibitors. Conclusion Newer studies evaluating rituximab showed little or no difference to early graft survival, and the efficacy of bortezomib and complement inhibitors for the treatment of AMR remains unclear. Despite the evidence uncertainty, plasmapheresis and IVIG have become standard-of-care for the treatment of acute AMR.