Evolution of the Definition of Rejection in Kidney Transplantation and Its Use as an Endpoint in Clinical Trials

Other authors

Institut Català de la Salut

[Becker JU] Institute of Pathology, University Hospital Cologne, Cologne, Germany. [Seron D] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rabant M] Department of Pathology, Hôpital Necker–Enfants Malades, Paris, France. [Roufosse C] Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom. [Naesens M] Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

Vall d'Hebron Barcelona Hospital Campus

Publication date

2023-01-09T18:16:32Z

2023-01-09T18:16:32Z

2022-05-20



Abstract

T cell-mediated rejection; Biopsy; Subclinical rejection


Rechazo mediado por células T; Biopsia; Rechazo subclínico


Rebuig mediat per cèl·lules T; Biòpsia; Rebuig subclínic


This article outlines the evolving definition of rejection following kidney transplantation. The viewpoints and evidence presented were included in documentation prepared for a Broad Scientific Advice request to the European Medicines Agency (EMA), relating to clinical trial endpoints in kidney transplantation. This request was initiated by the European Society for Organ Transplantation (ESOT) in 2016 and finalized following discussions between the EMA and ESOT in 2020. In ESOT’s opinion, the use of “biopsy-proven acute rejection” as an endpoint for clinical trials in kidney transplantation is no longer accurate, although it is still the approved histopathological endpoint. The spectrum of rejection is now divided into the phenotypes of borderline changes, T cell-mediated rejection, and antibody-mediated rejection, with the latter two phenotypes having further subclassifications. Rejection is also described in relation to graft (dys)function, diagnosed because of protocol (surveillance) or indication (for-cause) biopsies. The ongoing use of outdated terminology has become a potential barrier to clinical research in kidney transplantation. This article presents these perspectives and issues, and provides a foundation on which subsequent articles within this Special Issue of Transplant International build.


This initiative was supported by the European Society for Organ Transplantation.

Document Type

Article


Published version

Language

English

Publisher

Frontiers Media

Related items

Transplant International;35

https://doi.org/10.3389/ti.2022.10141

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Rights

Attribution 4.0 International

http://creativecommons.org/licenses/by/4.0/

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