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

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

Author information

1
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
2
William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota.
3
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
4
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
5
Terasaki Research Institute, Los Angeles, California.
6
Division of Transplantation Surgery, Mayo Clinic, Rochester, Minnesota.

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

PMID:
30412654
PMCID:
PMC6509017
[Available on 2020-06-01]
DOI:
10.1111/ajt.15175

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