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Antibody-mediated rejection-treatment standard.

Georg A Böhmig1, Maarten Naesens2, Ondrej Viklicky3

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Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
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Antibody-mediated rejection (AMR) treatments lack strong evidence. Current therapies like steroids and rituximab are not robustly supported, but new approaches targeting inflammation show promise for graft survival.

Keywords:
CD38antibody-mediated rejectionapheresisdonor-specific antibodynatural killer cells

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Area of Science:

  • Transplantation immunology
  • Nephrology
  • Graft survival research

Background:

  • Antibody-mediated rejection (AMR) is a primary driver of graft failure, imposing substantial clinical and economic burdens.
  • Despite decades of recognition, AMR treatment lacks standardization and regulatory-approved therapies.
  • Existing evidence for AMR treatments is limited, with many trials yielding negative results.

Purpose of the Study:

  • To critically re-evaluate the current evidence base for antibody-mediated rejection treatment strategies.
  • To inform clinical decision-making in the absence of robust, approved AMR therapies.
  • To identify promising therapeutic targets and approaches for future AMR treatment development.

Main Methods:

  • Systematic review and critical appraisal of existing clinical trial data for AMR treatments.
  • Analysis of expert consensus recommendations and their evidentiary basis.
  • Evaluation of emerging therapeutic strategies targeting AMR pathobiology.

Main Results:

  • Current evidence for steroids, rituximab, bortezomib, and IL-6 antagonists in AMR treatment is insufficient.
  • Immunoadsorption and potentially high-dose IVIG are considered for early AMR, with limited supporting data.
  • Emerging CD38 antibodies demonstrate potential by targeting endothelial inflammation, and complement inhibition is an option for severe early AMR.

Conclusions:

  • Robust evidence supporting common AMR treatments is lacking, necessitating a re-evaluation of clinical practice.
  • Novel therapies targeting cellular inflammation (e.g., CD38 antibodies) and complement pathways offer future hope.
  • Ongoing clinical trials for agents like efgartigimod, tocilizumab, and felzartamab may lead to approved, effective AMR treatments.