Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

Abstract

This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Parameter Summary Cumulative number of plasmapheresis treatments, N = 80 21 patients had ≥1 plasmapheresis treatment Day 0, mean (range) 0.1 (0-1) Week 9, mean (range) 1.0 (0-18) Month 12, mean (range) 2.5 (0-57) Delayed graft function a , N = 76 Yes, n (%) 13 (17.1) No, n (%) 63 (82.9) Cumulative incidence of the need for dialysis between day 7 and month 12, N = 48 Day 63, n (%) 1 (2.1) Day 90, n (%) 1 (2.1) Day 180, n (%) 2 (4.2) Day 364, n (%) 4 (8.3)

Ischemia and Reperfusion Injury in Kidney Transplantation: Relevant Mechanisms in Injury and Repair

“…All studies report a safety profile of the drug that is consistent with that reported for eculizumab's approved indications like atypical haemolytic uremic syndrome. Results of these trials suggest a potential role of eculizumab in the prevention and treatment of ABMR in patients with DSA [160,161]. Next to ABMR, eculizumab has been investigated for the prevention of DGF (NCT01919346, NCT02145182).…”

Upfront use of eculizumab to treat early acute antibody‐mediated rejection after kidney allotransplantation and relevance for xenotransplantation

“…Interestingly, only 12% of patients needed post‐transplant plasmapheresis in the eculizumab group, compared with 76% in controls. These important initial findings were the basis for two recent clinical trials, both reported in 2019, on eculizumab‐based induction to prevent early acute AMR in highly sensitized patients with preformed DSA 4,5 . In the single‐arm study of Glotz et al, 5 80 patients transplanted with C5 blockade during the first 9 weeks were compared with pooled analysis of acute AMR data derived from published data and similar results to the Stegall et al series 4 were found (an 8.8% incidence of acute AMR, that is, lower than the 40% expected rate for standard care (SOC) in such high immunological risk recipients).…”

“…Eculizumab is a humanized monoclonal antibody that binds to the human C5 complement protein, resulting in terminal complement blockade. Recently, the safety and efficacy of eculizumab to prevent early acute AMR has been studied prospectively in sensitized deceased‐donor and living‐donor kidney allotransplant recipients, suggesting a potential benefit for eculizumab, which was overall well tolerated 3‐5 . However, little is known about the upfront use of eculizumab to treat early and severe acute AMR in allotransplantation, because most reports to date using eculizumab in that setting (mainly as “rescue therapy”) have also included other treatments to remove circulating donor‐specific alloantibodies (DSA), such as plasmapheresis 6 or immunoadsorption and/or administration of intravenous immunoglobulins (IVIG) 2,6‐11 .…”

Outcomes of simultaneous pancreas and kidney transplantation based on donor resuscitation

“…Our primary outcomes were patient survival and all‐ and death‐censored graft survival. Kidney graft survival was defined as a functioning kidney without the need for dialysis and pancreas graft survival as a functioning exocrine pancreas without a permanent (>90 days) need for exogenous insulin . Cox proportional hazard regression was used to compare patient and graft survival between recipients of CACPR and non‐CACPR donors.…”