Long-term outcomes of eculizumab-treated positive crossmatch recipients: Allograft survival, histologic findings, and natural history of the donor-specific antibodies.
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.
['Schinstock|Carrie A|CA|0000-0002-3274-3277', 'Bentall|Andrew J|AJ|0000-0002-8495-9782', 'Smith|Byron H|BH|0000-0001-9318-2437', 'Cornell|Lynn D|LD|', 'Everly|Matthew|M|0000-0001-7392-5483', 'Gandhi|Manish J|MJ|0000-0001-6921-6123', 'Stegall|Mark D|MD|']
D000328:Adult D064591:Allografts D061067:Antibodies, Monoclonal, Humanized D001402:B-Lymphocytes D016022:Case-Control Studies D015922:Complement C1q D051056:Complement Inactivating Agents D005260:Female D006084:Graft Rejection D006085:Graft Survival D006680:HLA Antigens D006650:Histocompatibility Testing D006801:Humans D007518:Isoantibodies D007668:Kidney D016030:Kidney Transplantation D008297:Male D008875:Middle Aged D012189:Retrospective Studies D013997:Time Factors D014019:Tissue Donors D016896:Treatment Outcome
alloantibody clinical research/practice desensitization histocompatibility kidney transplantation/nephrology organ transplantation in general protocol biopsy rejection: antibody-mediated (ABMR) rejection: chronic