Terminal Complement Inhibition Decreases Antibody‐Mediated Rejection in Sensitized Renal Transplant Recipients

Sensitized renal transplant recipients with high levels of donor‐specific alloantibody (DSA) commonly develop antibody‐mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti‐C5 antib...

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Bibliographic Details
Published in:American journal of transplantation 2011-11, Vol.11 (11), p.2405-2413
Main Authors: Stegall, M. D., Diwan, T., Raghavaiah, S., Cornell, L. D., Burns, J., Dean, P. G., Cosio, F. G., Gandhi, M. J., Kremers, W., Gloor, J. M.
Format: Article
Language:English
Subjects:
Adult
Alloantibodies
Antibodies
Antibodies, Monoclonal, Humanized - therapeutic use
antibody‐mediated rejection
anti‐HLA antibodies
Biological and medical sciences
Biopsy
chronic rejection
complement
Complement activation
Complement C5 - antagonists & inhibitors
Complement Inactivating Agents - therapeutic use
Donors
Female
Graft rejection
Graft Rejection - immunology
Graft Rejection - prevention & control
Histocompatibility testing
Humans
Isoantibodies - blood
Kidney diseases
Kidney Transplantation
Living Donors
Male
Medical sciences
Middle Aged
Plasma Exchange
sensitized recipients
Splenectomy
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the urinary system
Survival
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Summary:Sensitized renal transplant recipients with high levels of donor‐specific alloantibody (DSA) commonly develop antibody‐mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti‐C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor. The incidence of biopsy‐proven AMR in the first 3 months posttransplant in 26 highly sensitized recipients of living donor renal transplants who received eculizumab posttransplant was compared to a historical control group of 51 sensitized patients treated with a similar plasma exchange (PE)‐based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031). Eculizumab also decreased AMR in patients who developed high levels of DSA early after transplantation that caused proximal complement activation. With eculizumab, AMR episodes were easily treated with PE reducing the need for splenectomy. On 1‐year protocol biopsy, transplant glomerulopathy was found to be present in 6.7% (1/15) eculizumab‐treated recipients and in 35.7% (15/42) of control patients (p = 0.044). Inhibition of terminal complement activation with eculizumab decreases the incidence of early AMR in sensitized renal transplant recipients (ClincalTrials.gov number NCT006707). This study demonstrates that the blockade of terminal complement activation with the C5‐specific antibody eculizumab decreases the incidence of early antibody‐mediated rejection in living donor renal transplant recipients who have high levels of donor specific alloantibody. See editorial by Woodle and Baldwin on page 2277.
ISSN:1600-6135
1600-6143
DOI:10.1111/j.1600-6143.2011.03757.x