Improvement in Paired Donation Program

配对捐赠计划的改进

• 批准号: 8450272
• 负责人: Stanislaw M Stepkowski
• 金额: $ 33万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8450272
• 关键词: ABO blood group system; Accounting; Address; Algorithms; American; Antibodies; Antigens; Area Under Curve; Binding; Biological Assay; Blood Group Incompatibility; Blood typing procedure; Cells; Complement-Dependent Cytotoxicity; Computer software; Country; Diagnosis; Diagnostic; Dialysis procedure; Donor Selection; End stage renal failure; Freezing; Generations; Gold; Grant; HLA Antigens; Histocompatibility; Immune; Immunogenetics; Immunoglobulin G; Kidney; Kidney Transplantation; Laboratories; Life; Living Donors; Location; Lymphocyte; Measures; Medicare; Memory; Methods; Ohio; Patients; Phase; Population; Proteins; Regulatory T-Lymphocyte; Running; Serum; Societies; Specificity; Testing; Time; Transplant Recipients; Transplantation; Travel; United States; blood group; computer program; computerized; cost; cost effective; cytotoxic; desensitization; improved; kidney allograft; killings; programs; public health relevance; screening; tool

DESCRIPTION (provided by applicant): The Alliance for Paired Donation (APD) makes possible the transplantation of kidneys from living donors who otherwise are not transplanted because of ABO blood group incompatibility and/or the presence of donor-specific antibodies (Abs; DSA) in sensitized patients. The APD program may facilitate selection of donors and recipients for 2000 patients. Living donation accounts for 45-50% (~6000/year) of all kidney transplants performed in the United States. For Ohio alone, out of 3,300 patients each year diagnosed with end-stage renal disease, 825 patients would have a willing living donor. Since one third of these willing donors are typically incompatible, 275 patients have willing but incompatible donors. Similar nationwide analysis would account each year for 2000 willing but incompatible pairs. The APD program, composed of 75 transplant programs in 27 states, has already performed ~50 transplants, including 10 transplants in the first "extended altruistic donor chain" that included one altruistic donor. The proposed project needs to address important issues: 1) to develop and validate diagnostic tools to perform crossmatches of recipients and donors who are in different locations; 2) to improve the computer program for the analysis of crossmatch results and other parameters; and 3) to efficiently validate the survival results. At the present time, two used crossmatch assays (flow crossmatch and complement-dependent cytotoxicity) require live donor cells. Instead, we need to adapt an assay allowing using donor lymphocyte extracts wherein donor HLA antigens are captured onto beads (Bead-HLA assay). The second assay uses beads pre-coated with donor-type proteins to detect single HLA reactive anybodies (Single-HLA assay). Both these assays will be validated against the flow crossmatch method. The project has three aims: Aim 1: To establish sensitive and reproducible screening methods. In the first phase, all 4 assays (two old and two new) will be run with sera from sensitized patients against 20-30 different donors (1800 combinations). Aim 2: To improve matching by APD computer program. The findings from Aim 1 will be incorporated into the software by calculating the area under the curve (AUC) for the specificity and selectivity values using the Simpson's rule numerical integration methods. Aim 3: To validate the survival results made by APD program. The survival results will be followed after transplantation to validate the quality of choices and to further improve the APD program. At the grant conclusion, we will establish a centralized screening center able to enlist up to 2000 new pairs per year. As each transplant saves $200,000 during 5 years as compared with dialysis - to say nothing of the improved life of the patient - this proposal is cost-effective.

描述（由申请人提供）：配对捐赠联盟 (APD) 使得活体捐赠者的肾脏移植成为可能，而这些捐赠者由于 ABO 血型不相容和/或存在捐赠者特异性抗体（Abs；DSA）而无法移植。在过敏患者中。 APD 计划可能有助于为 2000 名患者选择捐赠者和接受者。活体捐赠占美国所有肾移植手术的 45-50%（约 6000 例/年）。仅在俄亥俄州，每年就有 3,300 名被诊断患有终末期肾病的患者中，有 825 名患者有自愿的活体捐赠者。由于这些自愿捐献者中有三分之一通常不相容，因此 275 名患者有自愿但不相容的捐献者。类似的全国性分析每年都会对 2000 对愿意但不相容的伴侣进行统计。 APD 项目由 27 个州的 75 个移植项目组成，已经进行了约 50 例移植手术，其中包括第一个“扩展利他捐献者链”中的 10 例移植手术，其中包括一名利他捐献者。 拟议项目需要解决重要问题：1）开发和验证诊断工具，以对不同地点的接受者和捐赠者进行交叉匹配； 2) 改进交叉配血结果和其他参数分析的计算机程序； 3）有效验证生存结果。目前，两种使用的交叉配型测定（流式交叉配型和补体依赖性细胞毒性）需要活体供体细胞。相反，我们需要采用允许使用供体淋巴细胞提取物的测定法，其中供体 HLA 抗原被捕获到珠子上（珠子 HLA 测定法）。第二种检测使用预涂有供体型蛋白质的珠子来检测单个 HLA 反应性抗体（单 HLA 检测）。这两种测定都将根据流式交叉配血方法进行验证。该项目有三个目标： 目标 1：建立灵敏且可重复的筛查方法。在第一阶段，所有 4 项检测（两项旧的和两项新的）将使用来自致敏患者的血清针对 20-30 名不同的供体（1800 种组合）进行。目标 2：通过 APD 计算机程序改进匹配。目标 1 的结果将通过使用辛普森规则数值积分方法计算特异性和选择性值的曲线下面积 (AUC) 纳入软件中。目标3：验证APD程序得出的生存结果。移植后将跟踪生存结果，以验证选择的质量并进一步改进 APD 计划。 资助结束后，我们将建立一个集中筛选中心，每年能够招募多达 2000 对新人。与透析相比，每次移植在 5 年内可节省 20 万美元 - 更不用说改善患者的生活 - 这一建议具有成本效益。

项目成果

The 6-year clinical outcomes for patients registered in a multiregional United States Kidney Paired Donation program - a retrospective study.

在美国多区域肾脏配对捐赠计划中注册的患者的 6 年临床结果 - 一项回顾性研究。

• 发表时间: 2019-08
• 作者: Stepkowski, Stanislaw M;Mierzejewska, Beata;Fumo, David;Bekbolsynov, Dulat;Khuder, Sadik;Baum, Caitlin E;Brunner, Robert J;Kopke, Jonathan E;Rees, Susan E;Smith, Connie;Ashlagi, Itai;Roth, Alvin E;Rees, Michael A
• 通讯作者: Rees, Michael A

Utilization of Deceased Donor Kidneys to Initiate Living Donor Chains.

利用死亡捐赠肾脏启动活体捐赠链。

• 发表时间: 2016-05
• 作者: Melcher, M L;Roberts, J P;Leichtman, A B;Roth, A E;Rees, M A
• 通讯作者: Rees, M A

Historical Matching Strategies in Kidney Paired Donation: The 7-Year Evolution of a Web-Based Virtual Matching System.

肾脏配对捐赠的历史匹配策略：基于网络的虚拟匹配系统的 7 年演变。

• 发表时间: 2015-10
• 作者: Fumo, D E;Kapoor, V;Reece, L J;Stepkowski, S M;Kopke, J E;Rees, S E;Smith, C;Roth, A E;Leichtman, A B;Rees, M A
• 通讯作者: Rees, M A

Current approaches in national kidney paired donation programs.

国家肾脏配对捐赠计划的当前方法。

• 发表时间: 2013-03-19
• 作者: Mierzejewska, Beata;Durlik, Magdalena;Lisik, Wojciech;Baum, Caitlin;Schroder, Paul;Kopke, Jonathan;Rees, Michael;Stepkowski, Stanislaw
• 通讯作者: Stepkowski, Stanislaw

A Kidney Graft Survival Calculator that Accounts for Mismatches in Age, Sex, HLA, and Body Size.

肾移植存活率计算器，可考虑年龄、性别、HLA 和体型的不匹配。

• 发表时间: 2017-07-07
• 作者: Ashby, Valarie B;Leichtman, Alan B;Rees, Michael A;Song, Peter X;Bray, Mathieu;Wang, Wen;Kalbfleisch, John D
• 通讯作者: Kalbfleisch, John D