AUTHOR=Bestard Oriol , Thaunat Olivier , Bellini Maria Irene , Böhmig Georg A. , Budde Klemens , Claas Frans , Couzi Lionel , Furian Lucrezia , Heemann Uwe , Mamode Nizam , Oberbauer Rainer , Pengel Liset , Schneeberger Stefan , Naesens Maarten 

TITLE=Alloimmune Risk Stratification for Kidney Transplant Rejection

JOURNAL=Transplant International

VOLUME=Volume 35 - 2022

YEAR=2022

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2022.10138

DOI=10.3389/ti.2022.10138

ISSN=1432-2277

ABSTRACT=This paper outlines immunological and non-immunological risk stratification in kidney transplantation. The content was prepared by a working group within the European Society for Organ Transplantation (ESOT), which submitted a Broad Scientific Advice request to the European Medicines Agency (EMA) relating to clinical trial endpoints in kidney transplantation. After collaborative interactions with ESOT, the EMA sent its final response to this request in December 2020. Transplantations performed between human leukocyte antigen (HLA)-identical donors and recipients carry a significantly lower immunological risk than transplantations from HLA-mismatched donors. For the same allogeneic molecular HLA mismatch load, kidney grafts from living donors carry lower levels of immunological risk because they are better preserved and therefore less immunogenic than grafts from deceased donors. Single-antigen bead testing is the gold standard to establish the repertoire of serological sensitization and is used to define the presence of a recipient’s circulating donor-specific antibodies (HLA-DSA). In the absence of clinical validation, neither T/B cell ELISpot assays (for cellular memory) nor non–HLA-DSA screening assays should be considered when evaluating immunological risk before kidney transplantation. No routine clinical test can reliably measure innate immune alloreactivity. Molecular HLA mismatch analysis should help to further improve organ allocation compatibility and stratify immunological risk for primary alloimmune activation, but without consensus regarding which algorithm and cut-off to use, it is difficult to integrate such information immediately into clinical practice and study design.