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  • Review Article
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Strategies to overcome the ABO barrier in kidney transplantation

Nature Reviews Nephrology volume 11, pages 732–747 (2015)Cite this article

Subjects

Key Points

  • ABO-incompatible (ABOi) kidney transplantation is now an established treatment option for patients with end-stage renal disease, but the mechanisms that underlie acceptance of ABOi grafts are not well understood

  • The biology of the ABO system is complex; blood group subtypes and organ-specific patterns of core-chain tissue distribution require particular consideration in the context of ABOi transplantation

  • Innovative humanized animal models are expected to provide a better understanding of anti-A/B immune responses and might help to establish innovative therapeutic strategies to counteract blood-group-specific B-cell responses

  • The development of efficient desensitization protocols including apheresis, modulation of B-cell immunity and long-term maintenance immunosuppression has enabled ABOi kidney transplantation to become a safe treatment strategy with favourable outcomes

  • Although the reduction of pretransplant anti-A/B antibody titres below a permissive threshold is a major principle of desensitization, thresholds at which antibody-mediated damage can be predicted have not been defined

  • Tailoring the intensity of preconditioning for ABOi kidney transplant recipients according to their pretransplant anti-A/B antibody titres might be an efficient strategy to minimize the risks associated with enhanced immunosuppression

Abstract

Kidney transplantation across the ABO blood group barrier was long considered a contraindication for transplantation, but in an effort to increase donor pools, specific regimens for ABO-incompatible (ABOi) transplantation have been developed. These regimens are now widely used as an integral part of the available treatment options. Various desensitization protocols, commonly based on transient depletion of preformed anti-A and/or anti-B antibodies and modulation of B-cell immunity, enable excellent transplant outcomes, even in the long-term. Nevertheless, the molecular mechanisms behind transplant acceptance facilitated by a short course of anti-humoral treatment are still incompletely understood. With the evolution of efficient clinical programmes, tailoring of recipient preconditioning based on individual donor–recipient blood type combinations and the levels of pretransplant anti-A/B antibodies has become possible. In the context of low antibody titres and/or donor A2 phenotype, immunomodulation and/or apheresis might be dispensable. A concern still exists, however, that ABOi kidney transplantation is associated with an increased risk of surgical and infectious complications, partly owing to the effects of extracorporeal treatment and intensified immunosuppression. Nevertheless, a continuous improvement in desensitization strategies, with the aim of minimizing the immunosuppressive burden, might pave the way to clinical outcomes that are comparable to those achieved in ABO-compatible transplantation.

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Figure 1: The molecular structures and expression patterns of ABO antigens, showing blood group O, blood group A1, blood group A2, blood group B and blood group AB.
Figure 2: The molecular structures of A antigen core-chain isoforms.
Figure 3: Key elements of recipient desensitization in ABO-incompatible transplantation.
Figure 4: Apheresis techniques for anti-A/B antibody removal.

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Authors and Affiliations

  1. Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Georg A. Böhmig & Farsad Eskandary

  2. Department of Surgery, Section of Transplantation Immunology, Medical University of Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Andreas M. Farkas & Thomas Wekerle

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  1. Georg A. Böhmig
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  3. Farsad Eskandary
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All authors researched the data, made substantial contributions to discussions of the content, wrote the article and reviewed and edited the manuscript before submission.

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Böhmig, G., Farkas, A., Eskandary, F. et al. Strategies to overcome the ABO barrier in kidney transplantation. Nat Rev Nephrol 11, 732–747 (2015). https://doi.org/10.1038/nrneph.2015.144

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