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

Carrie Schinstock, Andrew Bentall, Byron H. Smith, Lynn D. Cornell, Matthew Everly, Manish J. Gandhi, Mark D Stegall

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Natural History
Allografts
Tissue Donors
Antibodies
B-Lymphocytes
Immunoglobulin G
Control Groups
Plasmapheresis
eculizumab
Observational Studies
Survival Rate
Retrospective Studies
Transplantation
Kidney
Antigens
Survival

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

@article{14564df46fdd43539a332a083d5046c7,
title = "Long-term outcomes of eculizumab-treated positive crossmatch recipients: Allograft survival, histologic findings, and natural history of the donor-specific antibodies",
abstract = "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",
author = "Carrie Schinstock and Andrew Bentall and Smith, {Byron H.} and Cornell, {Lynn D.} and Matthew Everly and Gandhi, {Manish J.} and Stegall, {Mark D}",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/ajt.15175",
language = "English (US)",
journal = "American Journal of Transplantation",
issn = "1600-6135",
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T1 - Long-term outcomes of eculizumab-treated positive crossmatch recipients

T2 - Allograft survival, histologic findings, and natural history of the donor-specific antibodies

AU - Schinstock, Carrie

AU - Bentall, Andrew

AU - Smith, Byron H.

AU - Cornell, Lynn D.

AU - Everly, Matthew

AU - Gandhi, Manish J.

AU - Stegall, Mark D

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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KW - desensitization

KW - histocompatibility

KW - kidney transplantation/nephrology

KW - organ transplantation in general

KW - protocol biopsy

KW - rejection: antibody-mediated (ABMR)

KW - rejection: chronic

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