Positive Long-Term Outcome of Kidney Allocation via Acceptable Mismatch Program in Highly Sensitized Patients

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-02-28 DOI:10.1159/000536533

Yara Strehler, N. Lachmann, M. Niemann, F. Halleck, K. Budde, Axel Pruß

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引用次数: 0

Abstract

Introduction: Eurotransplant established the acceptable mismatch (AM) program to facilitate timely kidney transplantations of highly sensitized patients, but long-term granular clinical and immunological outcomes regarding overall graft survival and de novo DSA (dnDSA) formation are still intensively researched. The right choice of induction therapy in patients with differing immunological risk is not conclusively determined, as well as the impact of human leukocyte antigen (HLA) epitope matching on dnDSA formation. Methods: This monocentric, retrospective study analyzed 94 patients transplanted within the AM program between 2000 and 2019 compared to case-control matched cohorts of non- (PRA 0–5%; PRA-0) and intermediately sensitized (PRA 6–84%; PRA-6/84) patients transplanted through Eurotransplant Kidney Allocation System. Results: Estimated 10-year overall graft survival between the PRA-0 and AM cohorts was similar, whereas PRA-6/84 was significantly disadvantageous compared to PRA-0. Estimated 10-year incidence of antibody-mediated rejection rates was significantly lower in the PRA-0 group compared to AM and PRA-6/84 groups. Compared to the AM group, estimated incidence of de novo donor-specific antibody (dnDSA) was significantly lower in PRA-0 patients, with no differences between the AM and PRA-6/84 cohorts. The PRA-6/84 cohort was the only subgroup in which interleukin-2 receptor antagonist (IL2RA) induction was associated with longer overall graft survival, patient survival, and graft survival compared to depleting induction (ATG or OKT3). Broad HLA-A, -B, -DR mismatches (mmABDR) and HLA epitope mismatches determined by Eplets and PIRCHE-II were predictive for dnDSA formation in the total cohort, and the AM subgroup. Discussion: The high efforts expended on AM patients are justified to allow timely organ transplantation with acceptable risk profile and non-inferior outcomes. IL2RA induction in intermediately sensitized patients is associated with superior overall graft survival, patient survival, and graft survival compared to ATG/OKT3 induction, without negative effects on rejection episodes or dnDSA formation. In silico epitope matching might further help reduce dnDSA formation, particularly in high-risk AM patients.

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高度敏感患者通过可接受错配方案进行肾脏分配的长期积极效果

导言：欧洲肾移植协会（Eurotransplant）制定了可接受的错配（AM）计划，以促进高度致敏患者及时进行肾移植，但有关总体移植存活率和新生DSA（dnDSA）形成的长期临床和免疫学结果仍在深入研究之中。对于免疫学风险不同的患者，诱导治疗的正确选择以及人类白细胞抗原（HLA）表位匹配对 dnDSA 形成的影响尚无定论。方法：这项单中心回顾性研究分析了 2000 年至 2019 年间在 AM 计划内移植的 94 例患者，并与通过欧洲肾移植分配系统移植的非致敏（PRA 0-5%；PRA-0）和中间致敏（PRA 6-84%；PRA-6/84）患者的病例对照匹配队列进行了比较。结果：PRA-0组和AM组的估计10年总体移植物存活率相似，而PRA-6/84组与PRA-0组相比明显处于劣势。与 AM 组和 PRA-6/84 组相比，PRA-0 组的估计 10 年抗体介导排斥发生率明显较低。与 AM 组相比，PRA-0 患者的新供体特异性抗体（dnDSA）估计发生率明显较低，而 AM 组和 PRA-6/84 组之间没有差异。与去势诱导（ATG 或 OKT3）相比，PRA-6/84 组是唯一一个白细胞介素-2 受体拮抗剂（IL2RA）诱导与较长的总移植物存活率、患者存活率和移植物存活率相关的亚组。通过Eplets和PIRCHE-II确定的广义HLA-A、-B、-DR错配（mmABDR）和HLA表位错配可预测整个队列和AM亚组中dnDSA的形成。讨论：为了能在风险可接受的情况下及时进行器官移植，并获得非劣效的治疗效果，对AM患者花费大量精力是合理的。与 ATG/OKT3 诱导相比，IL2RA 诱导中间致敏患者的总体移植物存活率、患者存活率和移植物存活率更高，且对排斥反应发作或 dnDSA 的形成没有负面影响。硅表位匹配可能会进一步帮助减少 dnDSA 的形成，尤其是在高风险 AM 患者中。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.