Use of Eculizumab for Active Antibody-mediated Rejection That Occurs Early Post–kidney Transplantation: A Consecutive Series of 15 Cases

Abstract

Background. Active antibody-mediated rejection (AMR) that occurs during the amnestic response within the first month posttransplant is a rare but devastating cause of early allograft loss after kidney transplant. Prior reports of eculizumab treatment for AMR have been in heterogeneous patient groups needing salvage therapy or presenting at varied time points. We investigated the role of eculizumab as primary therapy for active AMR early posttransplant. Methods. We performed a retrospective observational study of a consecutive cohort of solitary kidney transplant recipients who were transplanted between January 1, 2014, and January 31, 2018, and had AMR within the first 30 days posttransplant and treated with eculizumab ± plasmapheresis. Results. Fifteen patients had early active AMR at a median (interquartile range [IQR]) of 10 (7–11) days posttransplant and were treated with eculizumab ± plasmapheresis. Thirteen cases were biopsy proven, and 2 cases were presumed on the basis of donor-specific antibody trends and allograft function. Within 1 week of treatment, the median estimated glomerular filtration rate increased from 21 to 34 mL/min (P = 0.001); and persistent active AMR was only found in 16.7% (2/12) of biopsied patients within 4–6 months. No graft losses occurred, and at last follow-up (median [IQR] of 13 [12–19] mo), the median IQR estimated glomerular filtration rate increased to 52 (46–60) mL/min. Conclusions. Prompt eculizumab treatment as primary therapy is safe and effective for early active AMR after kidney transplant or abrupt increases in donor-specific antibodies when biopsy cannot be performed for diagnosis confirmation.

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

“…In particular, much was initially learned from the series of Stegall et al in 2011 3 where 26 highly sensitized patients with positive crossmatches (by flow cytometry) were transplanted with an eculizumab‐based induction protocol. Compared with a historical control group, they found that the incidence of acute AMR was reduced in the eculizumab group (7.7% vs 41.2%) 3,12,20 . All patient had thymoglobulin induction, and the majority of patients (69%) had pre‐transplant plasmapheresis.…”

“…Interestingly, in a recent retrospective analysis from the Mayo Clinic, 15 kidney allotransplant recipients were identified with early acute AMR within the first 30 days post‐transplant, all having an abrupt increase in donor‐specific antibodies (DSA) with rapid allograft dysfunction. Prompt eculizumab treatment, together with plasmapheresis in most cases, was found safe and effective for this type of early acute and active AMR, indicating that targeting C5 with immediate blockade of the terminal pathway of complement may be useful to prevent graft loss 12 …”

Novel strategies to target the humoral alloimmune response

“…137 A case series (N = 15) of early active ABMR treated with eculizumab plus PLEX as primary (rather than salvage) therapy also showed an impressive increase of median eGFR with no graft loss at minimum of 12-months follow-up. 138 The development of complement-targeting therapies is a fast evolving field and there are many new agents, which will require rigorous testing in transplantation (e.g., ravalizumab or anti-C1s antibody BIVV009). 139,140 Although the current evidence suggests efficacy for complement inhibitors in the treatment of ABMR, combination with DSA-reducing strategies to mitigate other non-complement-related DSA effector functions will likely be required.…”

Characteristics of Immunoglobulin M Type Antibodies of Different Origins from the Immunologic and Clinical Viewpoints and Their Application in Controlling Antibody-Mediated Allograft Rejection

“…Additionally, the effectiveness of anticomplement drugs for AMR treatment has also been reported. The administration of eculizumab, a humanized anti-C5 monoclonal antibody against active AMR, in the early stage after transplantation generally improved the pathological findings and function of transplanted grafts [ 140 ]. Eculizumab administration was also effective in preventing AMR development after transplantation, even in pre-DSA–positive cases of living kidney transplantation [ 141 ].…”