Report of the inefficacy of eculizumab in two cases of severe antibody-mediated rejection of renal grafts

Abstract

Background: Acute antibody-mediated rejection (AMR) is responsible for up to 20% to 30% of acute rejection after kidney transplantation. New therapeutic agents have recently emerged, such as eculizumab, an anticomplement protein-C5 monoclonal antibody. In the setting of renal transplantation, eculizumab has so far proved effective both for preventive and curative treatments of AMR in sensitized patients and patients diagnosed with severe AMR. Unsuccessful eculizumab treatment has only been reported once in the literature by Stegall et al. (Am J Transplant 2011; 11: 2405).

Methods and results: We present two cases of AMR resistant to eculizumab after renal transplantation. One patient received the anti-C5 antibody curatively, and the other patient developed AMR while being treated with eculizumab after a relapse of atypical hemolytic uremic syndrome. The peculiarity of these two cases was the absence of C4d deposition in peritubular capillaries as well as the absence of C1q-binding donor-specific anti-human leukocyte antigen alloantibody, as determined retrospectively, suggesting that a complement-independent mechanism underlies the pathogenesis of these AMR.

Conclusion: The use of eculizumab in C4d-negative or C1q-negative AMR does not seem effective.