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Improving Access to HLA-Matched Kidney Transplants for African American Patients

INTRODUCTION: Kidney transplants fail more often in Black than in non-Black (White, non-Black Hispanic, and Asian) recipients. We used the estimated physicochemical immunogenicity for polymorphic amino acids of donor/recipient HLAs to select weakly immunogenic kidney transplants for Black vs. White...

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Autores principales: Bekbolsynov, Dulat, Mierzejewska, Beata, Khuder, Sadik, Ekwenna, Obinna, Rees, Michael, Green, Robert C., Stepkowski, Stanislaw M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989073/
https://www.ncbi.nlm.nih.gov/pubmed/35401566
http://dx.doi.org/10.3389/fimmu.2022.832488
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author Bekbolsynov, Dulat
Mierzejewska, Beata
Khuder, Sadik
Ekwenna, Obinna
Rees, Michael
Green, Robert C.
Stepkowski, Stanislaw M.
author_facet Bekbolsynov, Dulat
Mierzejewska, Beata
Khuder, Sadik
Ekwenna, Obinna
Rees, Michael
Green, Robert C.
Stepkowski, Stanislaw M.
author_sort Bekbolsynov, Dulat
collection PubMed
description INTRODUCTION: Kidney transplants fail more often in Black than in non-Black (White, non-Black Hispanic, and Asian) recipients. We used the estimated physicochemical immunogenicity for polymorphic amino acids of donor/recipient HLAs to select weakly immunogenic kidney transplants for Black vs. White or non-Black patients. METHODS: OPTN data for 65,040 donor/recipient pairs over a 20-year period were used to calculate the individual physicochemical immunogenicity by hydrophobic, electrostatic and amino acid mismatch scores (HMS, EMS, AMS) and graft-survival outcomes for Black vs. White or vs. non-Black recipients, using Kaplan-Meier survival and Cox regression analyses. Simulations for re-matching recipients with donors were based on race-adjusted HMS thresholds with clinically achievable allocations. RESULTS: The retrospective median kidney graft survival was 12.0 years in Black vs. 18.6 years in White (6.6-year difference; p>0.001) and 18.4 years in non-Black (6.4-year difference; p>0.01) recipients. Only 0.7% of Blacks received transplants matched at HLA-A/B/DR/DQ (HMS=0) vs. 8.1% in Whites (p<0.001). Among fully matched Blacks (HMS=0), graft survival was 16.1-years and in well-matched Blacks (HMS ≤ 3.0) it was 14.0-years. Whites had 21.6-years survival at HMS ≤ 3.0 and 18.7-years at HMS ≤ 7.0 whereas non-Blacks had 22.0-year at HMS ≤ 3.0 and 18.7-year at HMS ≤ 7.0, confirming that higher HMS thresholds produced excellent survival. Simulation of ABO-compatible donor-recipient pairs using race-adjusted HMS thresholds identified weakly immunogenic matches at HMS=0 for 6.1% Blacks and 18.0% at HMS ≤ 3.0. Despite prioritizing Black patients, non-Black patients could be matched at the same level as in current allocation (47.0% vs 56.5%, at HMS ≤ 7.0). CONCLUSIONS: Race-adjusted HMS (EMS, AMS)-based allocation increased the number of weakly immunogenic donors for Black patients, while still providing excellent options for non-Black recipients.
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spelling pubmed-89890732022-04-08 Improving Access to HLA-Matched Kidney Transplants for African American Patients Bekbolsynov, Dulat Mierzejewska, Beata Khuder, Sadik Ekwenna, Obinna Rees, Michael Green, Robert C. Stepkowski, Stanislaw M. Front Immunol Immunology INTRODUCTION: Kidney transplants fail more often in Black than in non-Black (White, non-Black Hispanic, and Asian) recipients. We used the estimated physicochemical immunogenicity for polymorphic amino acids of donor/recipient HLAs to select weakly immunogenic kidney transplants for Black vs. White or non-Black patients. METHODS: OPTN data for 65,040 donor/recipient pairs over a 20-year period were used to calculate the individual physicochemical immunogenicity by hydrophobic, electrostatic and amino acid mismatch scores (HMS, EMS, AMS) and graft-survival outcomes for Black vs. White or vs. non-Black recipients, using Kaplan-Meier survival and Cox regression analyses. Simulations for re-matching recipients with donors were based on race-adjusted HMS thresholds with clinically achievable allocations. RESULTS: The retrospective median kidney graft survival was 12.0 years in Black vs. 18.6 years in White (6.6-year difference; p>0.001) and 18.4 years in non-Black (6.4-year difference; p>0.01) recipients. Only 0.7% of Blacks received transplants matched at HLA-A/B/DR/DQ (HMS=0) vs. 8.1% in Whites (p<0.001). Among fully matched Blacks (HMS=0), graft survival was 16.1-years and in well-matched Blacks (HMS ≤ 3.0) it was 14.0-years. Whites had 21.6-years survival at HMS ≤ 3.0 and 18.7-years at HMS ≤ 7.0 whereas non-Blacks had 22.0-year at HMS ≤ 3.0 and 18.7-year at HMS ≤ 7.0, confirming that higher HMS thresholds produced excellent survival. Simulation of ABO-compatible donor-recipient pairs using race-adjusted HMS thresholds identified weakly immunogenic matches at HMS=0 for 6.1% Blacks and 18.0% at HMS ≤ 3.0. Despite prioritizing Black patients, non-Black patients could be matched at the same level as in current allocation (47.0% vs 56.5%, at HMS ≤ 7.0). CONCLUSIONS: Race-adjusted HMS (EMS, AMS)-based allocation increased the number of weakly immunogenic donors for Black patients, while still providing excellent options for non-Black recipients. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8989073/ /pubmed/35401566 http://dx.doi.org/10.3389/fimmu.2022.832488 Text en Copyright © 2022 Bekbolsynov, Mierzejewska, Khuder, Ekwenna, Rees, Green and Stepkowski 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 Immunology
Bekbolsynov, Dulat
Mierzejewska, Beata
Khuder, Sadik
Ekwenna, Obinna
Rees, Michael
Green, Robert C.
Stepkowski, Stanislaw M.
Improving Access to HLA-Matched Kidney Transplants for African American Patients
title Improving Access to HLA-Matched Kidney Transplants for African American Patients
title_full Improving Access to HLA-Matched Kidney Transplants for African American Patients
title_fullStr Improving Access to HLA-Matched Kidney Transplants for African American Patients
title_full_unstemmed Improving Access to HLA-Matched Kidney Transplants for African American Patients
title_short Improving Access to HLA-Matched Kidney Transplants for African American Patients
title_sort improving access to hla-matched kidney transplants for african american patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989073/
https://www.ncbi.nlm.nih.gov/pubmed/35401566
http://dx.doi.org/10.3389/fimmu.2022.832488
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