Balancing equity and human leukocyte antigen matching in deceased-donor kidney allocation with eplet mismatch.

IF 8.9 2区 医学 Q1 SURGERY American Journal of Transplantation Pub Date : 2024-12-02 DOI:10.1016/j.ajt.2024.11.030
Michal A Mankowski, Loren Gragert, Brendan Keating, Bonnie E Lonze, Dorry L Segev, Robert Montgomery, Sommer E Gentry, Massimo Mangiola
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Abstract

Human leukocyte antigen-level matching in US kidney allocation has been deemphasized due to its role in elevating racial disparities. Molecular matching based on eplets might improve risk stratification compared to antigen matching, but the magnitude of racial disparities in molecular matching is not known. To assign eplets unambiguously, we utilized a cohort of 5193 individuals with high-resolution allele-level human leukocyte antigen genotypes from the National Kidney Registry. Using repeated random sampling to simulate donor-recipient genotype pairings based on the ethnic composition of the historical US deceased-donor pool, we profiled the percentage of well-matched donors available for candidates by ethnicity. The prevalence of well-matched donors with 0-DR/DQ eplet mismatch was 3-fold less racially disparate for Black and Asian candidates and 2-fold less for Latino candidates compared to 0-ABDR antigen mismatches. Compared to 0-DR antigen mismatch, 0-DR eplet mismatch was 1.33-fold more racially disparate for Asian and 1.28-fold more for Latino, with similar disparity for Black candidates, whereas 0-DQ eplet mismatch reduced disparities, showing 1.26-fold less disparity for Black, 1.14-fold less for Latino, but 1.26-fold higher for Asian candidates. The prevalence of well-matched donors for candidates of different ethnicities varied according to which molecules were chosen to define a low-risk match.

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在Eplet配错的死亡供者肾脏分配中平衡公平和HLA匹配。
HLA抗原水平匹配在美国肾脏分配中已被淡化,因为它在加剧种族差异中的作用。与抗原匹配相比,基于eplets的分子匹配可能改善风险分层,但分子匹配的种族差异程度尚不清楚。为了明确地分配eplets,我们使用了来自国家肾脏登记处的5193名具有高分辨率等位基因水平HLA基因型的个体。根据美国历史上已故供体的种族组成,我们使用重复随机抽样来模拟供体-受体基因型配对,并按种族描述了候选人可获得的匹配良好的供体的百分比。与零abdr抗原错配相比,匹配良好的供者与零dr /DQ基因不匹配的比例在黑人和亚洲候选人中降低了3倍,在拉丁裔候选人中降低了2倍。与零dr抗原错配相比,零dr抗原错配在亚裔和拉丁裔候选人中分别高出1.33倍和1.28倍,黑人候选人中也存在类似的差异,而零dq抗原错配降低了差异,黑人候选人的差异减少了1.26倍,拉丁裔候选人的差异减少了1.14倍,但亚裔候选人的差异增加了1.26倍。根据选择的分子来定义低风险匹配,不同种族候选人匹配良好的供体的流行程度有所不同。
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来源期刊
CiteScore
18.70
自引率
4.50%
发文量
346
审稿时长
26 days
期刊介绍: The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide. The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.
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