Eculizumab in renal transplantation

https://doi.org/10.1016/j.trre.2013.04.002Get rights and content

Abstract

Antibody-mediated rejection, be it acute, subacute or chronic, is currently recognized as the major cause of graft loss in kidney transplant recipients. Anti-HLA donor-specific antibodies are deleterious to the graft fate whether they pre-exist to the transplantation or appear in the course of transplantation. The role of complement is therefore prominent in most instances. As well, the role of complement activation is crucial in the recurrence of atypical hemolytic uremic syndrome post-transplantation (aHUS) as well as following ischemia-reperfusion injury leading to delayed graft function.

Eculizumab, a fully humanized monoclonal antibody directed against the C5 component of the complement cascade is efficient in chronically and safely blocking complement activation for example in paroxysmal nocturnal hemoglobinuria.

In the setting of kidney transplantation, there is convincing but still limited evidence that eculizumab is efficient in preventing both acute and chronic antibody-mediated rejection in highly sensitized recipients requiring desensitization before getting a living donor kidney transplant. Studies are currently ongoing to determine its efficacy and safety in ABO incompatible transplantation, in the prevention of acute and chronic rejection either with a living or a deceased donor kidney as well as in the prevention of delayed graft function.

Similar to its efficacy in aHUS on native kidneys, eculizumab prevents or treats recurrence after kidney transplantation.

There is still a lot of research to be performed in order to determine precisely the exact indications and the length of treatment with this very active but also very expensive drug that will undoubtedly revolutionize the current management of patients with donor specific antibodies (DSAs) and at risk of HUS recurrence.

References (26)

  • C. Lefaucheur et al.

    Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation

    J Am Soc Nephrol

    (2010)
  • N. Lachmann et al.

    Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts

    Transplantation

    (2009)
  • A. Loupy et al.

    The impact of donor-specific anti-HLA antibodies on late kidney allograft failure

    Nat Rev Nephrol

    (2012)
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      Both clinical and subclinical antibody-mediated rejection have been recognized as major causes of allograft loss (Amico et al., 2009), which is usually unresponsive to conventional anti-rejection therapy, such as suppression of the T-cell-dependent antibody response, removal of donor reactive antibodies, blocking residual allo-antibodies, and depletion of naive and memory B-cells. Convincing, but still limited, evidence has shown that eculizumab is efficient in preventing both acute and chronic antibody-mediated rejection and clinical studies further extending these results are ongoing (Legendre et al., 2013). Graft-versus-host disease (GvHD) is at the other side of the spectrum of clinical complications of allo-transplantation and is mediated by donor T-cells that attack host cells, leading to epithelial tissue injury in skin, intestine, and liver (Shlomchik, 2007).

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