The Treatment of Acute Antibody-Mediated Rejection in Kidney Transplant Recipients-A Systematic Review

1 Statewide Renal Services, Royal Prince Alfred and Concord Repatriation General Hospitals, New South Wales, Australia. 2 School of Medicine, University of Queensland, Herston, Queensland, Australia. 3 School of Medicine, University of Sydney, Camperdown, New South Wales, Australia. 4 Address correspondence to: Darren M. Roberts, M.B.B.S., Ph.D., F.R.A.C.P., Statewide renal services, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050.
Transplantation (Impact Factor: 3.83). 10/2012; 94(8):775-83. DOI: 10.1097/TP.0b013e31825d1587
Source: PubMed


Antibody-mediated rejection (AMR) is a recognized cause of allograft loss in kidney transplant recipients. A range of therapies targeting removal of circulating donor-specific antibodies (DSAs), blocking their effect or reducing production have been reported.
We conducted a systematic review to determine the efficacy of treatments for acute AMR in renal allografts. Electronic databases, reference lists, and conference proceedings were searched for controlled trials. Nonrandomized publications were reviewed for the purpose of discussion.
We identified 10,388 citations, including five randomized and seven nonrandomized controlled trials. The randomized studies were small (median, 13 patients/arm; range, 5-23), of which, four examined plasmapheresis (one suggested benefit) and one for immunoadsorption (also suggesting benefit). Marked heterogeneity was evident, including the definition and severity of AMR and the treatment regimen. The end point of graft survival was common to all studies. Small, nonrandomized controlled studies suggested benefit from rituximab or bortezomib. The effects of dose and regimen on the clinical response to any of the current treatments were not apparent from the available data.
Data describing the efficacy of treatments for AMR in renal allografts are of low or very low quality. Larger randomized controlled trials and dose-response studies are required.

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    • "Major advances have been made in controlling T-cell-mediated allograft rejection (Nankivell & Alexander 2010). However, this success has revealed the presence of significant levels of humoral allograft rejection driven by pre-existing or de novo donor-specific antibodies which is poorly controlled by current therapies (Roberts et al. 2012). Thus, there is a major unmet medical need for new therapeutic options in the treatment of antibody-dependent allograft rejection. "
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