Eculizumab Therapy for Chronic Antibody Mediated Rejection
Chronic antibody mediated rejection (AMR) is currently a major problem in kidney transplantation. Chronic AMR results in poor graft survival and there are no effective therapies. To date the best data on treatment exists with rituximab and IVIg, although still limited. Eculizumab, a humanized monoclonal antibody against C5, is FDA approved to treat PNH and atypical HUS. It blocks the terminal pathway of complement, which happens to be the mechanism of antibody mediated injury in kidney transplant recipients. In addition, it modulates the immune system by inhibiting the formation of a potent aphlatoxin, C5a. It then stands to reason that chronic treatment with eculizumab may slow down antibody mediated injury. Dr. Kulkarni from Yale presented his preliminary data on his randomized control trial comparing the use of eculizumab to placebo.
Dr. Kulkarni mentioned that at the time of his presentation 14 patients have been enrolled; however, he presented data on 4 patients treated with eculizumab and 2 controls. Patients treated with eculizumab where divided into patients who were C4D positive on kidney biopsy and those who were C4D negative. In the C4D treatment group, GFR stabilized while being treated then deteriorated once eculizumab treatment was stopped. The C4D negative group had similar changes although not as obvious. In comparison, both control patients reached ESRD by 12 months into the study. The authors also evaluated endothelial cell transcripts such as e-selectin which did not change during treatment.
Although much too early to make any conclusion on the efficacy of eculizumab in chronic AMR, this will be a very interesting study to follow.
Post written by Dr. Vinay Nair, eAJKD Advisory Board member.
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