February 23, 2012

Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients


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Antibody-mediated rejection (ABMR)in the presence of high levels of donor-specific antibodies (DSA) likely involves complement activation as part of the mechanism of graft damage. This study examined the efficacy of inhibiting complement activation by neutralizing C5 with a humanized anti-C5 antibody; eculizumab. The effect of anti-C5 treatment was assessed in 26 highly sensitized recipients of living donor transplants and compared to sensitized patients treated with plasma exchange (PE). Anti-C5 treatment reduced the incidence of ABMR compared to PE (7.7% versus 41.2%) and also made severe ABMR episodes easily treatable with PE. The incidence of transplant glomerulopathy, often associated with late antibody-mediated damage, was also lower in 1-year protocol biopsies. Inhibition of complement activation may prove to be an effective therapy for early ABMR often observed in highly sensitized patients transplanted across positive cross-matches. However, longer term follow-up is required to determine if this type of treatment can improve long-term graft survival.

Renal Transplantation

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