Eculizumab Therapy for Chronic Antibody-Mediated Injury in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial

Am J Transplant. 2017 Mar;17(3):682-691. doi: 10.1111/ajt.14001. Epub 2016 Sep 16.


We hypothesized that de novo donor-specific antibody (DSA) causes complement-dependent endothelial cell injury in kidney transplants, as assessed by expression of endothelial cell-associated transcripts (ENDATs), that may be attenuated through complement inhibition. In total, 15 participants (five control, 10 treatment) with DSA and deteriorating renal function were enrolled. The treatment group received 6 mo of eculizumab followed by 6 mo of observation, whereas controls were observed. The primary end point was percentage change in estimated GFR (eGFR) trajectory over the treatment period. The treatment group had an improved eGFR trajectory versus control, based on our predetermined two-sided 0.10 significance level (p = 0.09). Within-subject analysis of treated participants at 6-mo intervals did not show significant change (p = 0.60). Modeling C1q status showed that C1q-positive patients had significantly higher mean eGFR than patients with negative C1q (p = 0.04). Biopsies revealed elevated renal ENDATs in most participants, but ENDATs were not reduced with complement inhibition. Our data suggest that eculizumab treatment may stabilize kidney function in patients with chronic persistent DSA based on our pilot a priori significance threshold. ENDAT expression predicative of acute humoral injury is not reduced with complement inhibition in this chronic setting. Further studies will be necessary to determine which patients may benefit from eculizumab.

Keywords: alloantibody; basic (laboratory) research/science; chronic allograft nephropathy; clinical research/practice; clinical trial; complement biology; kidney failure/injury; kidney transplantation/nephrology.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Chronic Disease
  • Complement C5 / antagonists & inhibitors
  • Complement Inactivating Agents / therapeutic use
  • Early Intervention, Educational
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Survival / drug effects*
  • Graft Survival / immunology
  • Humans
  • Isoantibodies / blood*
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Living Donors
  • Male
  • Middle Aged
  • Pilot Projects
  • Prognosis
  • Risk Factors
  • Tissue Donors
  • Transplant Recipients
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Complement C5
  • Complement Inactivating Agents
  • Isoantibodies
  • eculizumab