title: Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation.
abstract: BACKGROUND
  Incompatible live donor kidney transplantation is associated with an increased rate of antibody-mediated rejection (AMR) and subsequent transplant glomerulopathy. For patients with severe, oliguric AMR, graft loss is inevitable without timely intervention.
  
  
  METHODS
  We reviewed our experience rescuing kidney allografts with this severe AMR phenotype by using splenectomy alone (n=14), eculizumab alone (n=5), or splenectomy plus eculizumab (n=5), in addition to plasmapheresis.
  
  
  RESULTS
  The study population was 267 consecutive patients with donor-specific antibody undergoing desensitization. In the first 3 weeks after transplantation (median=6 days), 24 patients developed sudden onset oliguria and rapidly rising serum creatinine with marked rebound of donor-specific antibody, and a biopsy that showed features of AMR. At a median follow-up of 533 days, 4 of 14 splenectomy-alone patients experienced graft loss (median=320 days), compared to four of five eculizumab-alone patients with graft failure (median=95 days). No patients treated with splenectomy plus eculizumab experienced graft loss. There was more chronic glomerulopathy in the splenectomy-alone and eculizumab-alone groups at 1 year, whereas splenectomy plus eculizumab patients had almost no transplant glomerulopathy.
  
  
  CONCLUSIONS
  These data suggest that for patients manifesting early severe AMR, splenectomy plus eculizumab may provide an effective intervention for rescuing and preserving allograft function.
authors.affiliation: 1 Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD. 2 Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD. 3 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. 4 Department of Surgery, University of Alabama, Birmingham, AL. 5 Address correspondence to: Robert Montgomery, M.D., DPhil, 720 Rutland Avenue, Ross 765, Baltimore, MD 21205.
authors.forename: Babak J
authors.initials: BJ
authors.lastname: Orandi
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
authors.forename: Nabil N
authors.initials: NN
authors.lastname: Dagher
authors.forename: Serena M
authors.initials: SM
authors.lastname: Bagnasco
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Garonzik-Wang
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Van Arendonk
authors.forename: Natasha
authors.initials: N
authors.lastname: Gupta
authors.forename: Bonnie E
authors.initials: BE
authors.lastname: Lonze
authors.forename: Nada
authors.initials: N
authors.lastname: Alachkar
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kraus
authors.forename: Niraj M
authors.initials: NM
authors.lastname: Desai
authors.forename: Jayme E
authors.initials: JE
authors.lastname: Locke
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Racusen
authors.forename: Dorry L
authors.initials: DL
authors.lastname: Segev
authors.forename: Robert A
authors.initials: RA
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology; D016879:Salvage Therapy; D013156:Splenectomy
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007518:Isoantibodies; C481642:eculizumab