Eculizumab for Thrombotic Microangiopathy Associated with Antibody-Mediated Rejection after ABO-Incompatible Kidney Transplantation

Abstract

Thrombotic microangiopathy is a form of antibody-mediated rejection (ABMR): it is the main complication of ABO-incompatible (ABOi) kidney transplantation (KT). Herein, we report on two cases of ABMR with biological and histological features of thrombotic microangiopathy (TMA) that were treated by eculizumab after ABOi KT. The first patient presented with features of TMA at postoperative day (POD) 13. Because of worsening biological parameters and no recovery of kidney function, despite seven sessions of immunoadsorption, a salvage therapy of eculizumab was started on POD 23. Kidney function slightly improved during the first 4 months after transplantation. Eculizumab was stopped at month 4. However, kidney function worsened progressively, leading to dialysis at month 13 after transplantation. The second patient presented with features of TMA at POD 1. In addition to immunoadsorption therapy, eculizumab was started on POD 6. Kidney function improved. Eculizumab was stopped on POD 64 and immunoadsorption sessions were stopped on POD 102. At the last follow-up (after 9 months), eGFR was at 43 mL/min/1.73 m2. Our case reports show the beneficial effect of eculizumab to treat ABMR after ABOi KT. However, it should be given early after diagnosing TMA associated with ABMR.

ABO‐incompatible living kidney transplantation

“…Despite ABO antigen‐antibody binding, the upregulation of the complement inhibitor might contribute to circumventing sdTMA or AMR in the acute phase after ABO‐ILKT, which may help explain the absence of clinical signs 64 . Anti‐complement therapy with eculizumab was proven to be effective in some cases, which also confirmed the significance of complement regulatory genes in sdTMA 65 . Costimulation blockage with belatacept provides an effective alternate immunosuppressive strategy for these patients 66 .…”

Anti‐IL‐2R blockers comparing with polyclonal antibodies: Higher risk of rejection without negative mid‐term outcomes after ABO‐incompatible kidney transplantation

“…Indeed, several studies have shown that replication is less frequent in kidney transplant patients given everolimus rather than MPA associated with CNIs. In addition, we had previously observed that switching from mycophenolic acid to everolimus in ABOi LDKT patients with BKV replication allowed BKV clearance …”

“…In a recent single‐center retrospective study, Lonze et al found that patients who experience an AMR within the first month after ABOi kidney transplant have a six‐fold increase in the incidence of late AMR (IRR = 6.3, [95% CI: 1.6‐24.6], P = .008). Late AMR is known to reduce kidney allograft survival . Moreover, in a recent meta‐analysis comparing ABO‐incompatible living donor kidney transplantation compared to center‐matched ABO‐compatible control patients, ABO‐incompatible kidney transplant recipients presented a higher risk of graft loss during the first year and antibody‐mediated rejection or infections .…”

Komplementinhibitoren: neue Therapeutika – neue Indikationen

“…B. Plasmapherese oder intravenös verabreichten Immunglobulinen) [56]. Kasuistiken berichten über die positive Wirkung von Eculizumab auf eine transplantationsassoziierte TMA, welche nach Nierentransplantation im Kontext einer AB0-inkompatiblen Transplantation aufgetreten ist [57] und schwangerschaftsassoziierter TMA [58] und dem Antiphospholipidsyndrom [59].…”