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Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption

Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From Marc...

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Autores principales: Kälble, Florian, Süsal, Caner, Pego da Silva, Luiza, Speer, Claudius, Benning, Louise, Nusshag, Christian, Pham, Lien, Tran, Hien, Schaier, Matthias, Sommerer, Claudia, Beimler, Jörg, Mehrabi, Arianeb, Zeier, Martin, Morath, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719417/
https://www.ncbi.nlm.nih.gov/pubmed/34977083
http://dx.doi.org/10.3389/fmed.2021.781491
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author Kälble, Florian
Süsal, Caner
Pego da Silva, Luiza
Speer, Claudius
Benning, Louise
Nusshag, Christian
Pham, Lien
Tran, Hien
Schaier, Matthias
Sommerer, Claudia
Beimler, Jörg
Mehrabi, Arianeb
Zeier, Martin
Morath, Christian
author_facet Kälble, Florian
Süsal, Caner
Pego da Silva, Luiza
Speer, Claudius
Benning, Louise
Nusshag, Christian
Pham, Lien
Tran, Hien
Schaier, Matthias
Sommerer, Claudia
Beimler, Jörg
Mehrabi, Arianeb
Zeier, Martin
Morath, Christian
author_sort Kälble, Florian
collection PubMed
description Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.
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spelling pubmed-87194172022-01-01 Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption Kälble, Florian Süsal, Caner Pego da Silva, Luiza Speer, Claudius Benning, Louise Nusshag, Christian Pham, Lien Tran, Hien Schaier, Matthias Sommerer, Claudia Beimler, Jörg Mehrabi, Arianeb Zeier, Martin Morath, Christian Front Med (Lausanne) Medicine Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss. Frontiers Media S.A. 2021-12-17 /pmc/articles/PMC8719417/ /pubmed/34977083 http://dx.doi.org/10.3389/fmed.2021.781491 Text en Copyright © 2021 Kälble, Süsal, Pego da Silva, Speer, Benning, Nusshag, Pham, Tran, Schaier, Sommerer, Beimler, Mehrabi, Zeier and Morath. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Kälble, Florian
Süsal, Caner
Pego da Silva, Luiza
Speer, Claudius
Benning, Louise
Nusshag, Christian
Pham, Lien
Tran, Hien
Schaier, Matthias
Sommerer, Claudia
Beimler, Jörg
Mehrabi, Arianeb
Zeier, Martin
Morath, Christian
Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption
title Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption
title_full Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption
title_fullStr Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption
title_full_unstemmed Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption
title_short Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption
title_sort living donor kidney transplantation in patients with donor-specific hla antibodies after desensitization with immunoadsorption
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719417/
https://www.ncbi.nlm.nih.gov/pubmed/34977083
http://dx.doi.org/10.3389/fmed.2021.781491
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