Improvement in Paired Donation Program

配对捐赠计划的改进

• 批准号: 8259816
• 负责人: Stanislaw M Stepkowski
• 金额: $ 35.11万
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8259816
• 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; Screening procedure; 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; 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. PUBLIC HEALTH RELEVANCE: The application addresses very important public need to develop national Kidney Paired Donation program, a new strategy to help end-stage renal disease patients who have willing but incompatible living donors. We have already developed a sophisticated computerized algorithm and advanced laboratory methods to match the incompatible donor/recipient pair to other pair in the country, in such fashion that they become compatible. Up to 2000 new pairs can be matched in this program, saving Medicare more than $200,000 over 5 years for each transplanted patients compared to the dialysis cost.

描述（由申请人提供）：配对捐赠的联盟（APD）使来自活捐赠者的肾脏可以移植，否则这些捐助者因ABO血液组不相容和/或在敏化患者中的存在而没有移植，并且存在供体特异性抗体（ABS; DSA）。 APD计划可以促进2000名患者的捐助者和接受者的选择。在美国进行的所有肾脏移植物中，生活捐赠占45-50％（〜6000）。仅俄亥俄州，在每年诊断出患有末期肾脏疾病的3300名患者中，有825名患者将有一个愿意的活体供体。由于这些愿意的捐助者中有三分之一通常不兼容，因此有275名患者愿意但不兼容的捐助者。在全国范围内，类似的全国分析将考虑2000年愿意但不兼容的对。 APD计划由27个州的75个移植计划组成，已经进行了约50次移植，其中包括第一个“扩展的无私供体链”中的10次移植，其中包括一个无私的供体。 拟议的项目需要解决重要问题：1）开发和验证诊断工具，以执行不同位置的接收者和捐助者的交叉匹配； 2）改进计算机程序，以分析交叉匹配结果和其他参数； 3）有效验证生存结果。目前，两个使用的交叉匹配测定（流交叉匹配和补体依赖性细胞毒性）需要活细胞。取而代之的是，我们需要调整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（珠HLA分析）上。第二种测定使用与供体类型蛋白预先涂覆的珠子来检测单个HLA反应性任何繁殖体（单HLA分析）。这两种测定法都将通过流相交方法验证。该项目具有三个目标：目标1：建立敏感和可重复的筛选方法。在第一阶段，所有4种测定（两个古老和两个新的测定法）将与20-30名不同供体（1800个组合）的敏化患者的血清进行。目标2：通过APD计算机程序改进匹配。 AIM 1的发现将通过使用Simpson的规则数值集成方法计算曲线（AUC）下的区域（AUC）下的区域（AUC）来纳入软件。目标3：验证APD计划的生存结果。移植后将遵循生存结果，以验证选择质量并进一步改善APD计划。 在赠款的结论中，我们将建立一个集中式筛选中心，每年最多可以入伍2000对新对。由于与透析相比，每次移植在5年内节省了200,000美元 - 不用说病人的寿命改善，因此该提案具有成本效益。 公共卫生相关性：该申请旨在解决公众开发国家肾脏配对捐赠计划的非常重要的需求，这是一种新的策略，旨在帮助末期肾脏疾病患者愿意但不兼容的活人捐助者。我们已经开发了一种复杂的计算机化算法和高级实验室方法，以使不兼容的捐助者/接收者对与该国的其他对，以使它们变得兼容。该计划可以匹配到2000个新对，与透析成本相比，每个移植的患者在5年内为Medicare节省了超过200,000美元。