Long-term outcomes of eculizumab-treated positive crossmatch recipients: Allograft survival, histologic findings, and natural history of the donor-specific antibodies

Am J Transplant. 2019 Jun;19(6):1671-1683. doi: 10.1111/ajt.15175. Epub 2018 Dec 15.


We aimed to determine the long-term outcomes of eculizumab-treated, positive crossmatch (+XM) kidney transplant recipients compared with +XM and age-matched negative crossmatch (-XM) controls. We performed an observational retrospective study and examined allograft survival, histologic findings, long-term B-cell flow cytometric XM (BFXM), and allograft-loss-associated factors. The mean (SD) posttransplant follow-up was 6.3 (2.5) years in the eculizumab group; 7.6 (3.5), +XM control group; 7.9 (2.5), -XM control group. The overall and death-censored allograft survival rates were similar in +XM groups (P = .73, P = .48) but reduced compared with -XM control patients (P < .001, P < .001). In the eculizumab-treated group, 57.9% (11/19) of the allografts had chronic antibody-mediated rejection, but death-censored allograft survival was 76.6%, 5 years; 75.4%, 7 years. Baseline IgG3 positivity and BFXM ≥300 were associated with allograft loss. C1q positivity was also associated with allograft loss but did not reach statistical significance. Donor-specific antibodies appeared to decrease in eculizumab-treated patients. After excluding patients with posttransplant plasmapheresis, 42.3% (9/21) had negative BFXMs; 31.8% (7/22), completely negative single-antigen beads 1 year posttransplant. Eculizumab-treated +XM patients had reduced allograft survival compared with -XM controls but similar survival to +XM controls. BFXM and complement-activating donor-specific antibodies (by IgG3 and C1q testing) may be used for risk stratification in +XM transplantation.

Keywords: alloantibody; clinical research/practice; desensitization; histocompatibility; kidney transplantation/nephrology; organ transplantation in general; protocol biopsy; rejection: antibody-mediated (ABMR); rejection: chronic.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Allografts
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Complement C1q / metabolism
  • Complement Inactivating Agents / therapeutic use*
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival / immunology
  • HLA Antigens / immunology
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / blood
  • Kidney / immunology
  • Kidney / pathology
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Time Factors
  • Tissue Donors
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • HLA Antigens
  • Isoantibodies
  • Complement C1q
  • eculizumab