Collaborative Research: SCH: Optimal Desensitization Protocol in Support of a Kidney Paired Donation (KPD) System

合作研究：SCH：支持肾脏配对捐赠 (KPD) 系统的最佳脱敏方案

• 批准号: 2123685
• 负责人: Monica Gentili
• 金额: $ 15.97万
• 依托单位: University of Louisville Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2123685&HistoricalAwards=false
• 关键词: Collaborative; Research; SCH; Optimal; Desensitization

This Smart and Connected Health (SCH) award will contribute to improved patient access to kidney transplantation by studying the inclusion of a personalized antibody removal regimen known as “desensitization” into a kidney paired donation (KPD) system. Kidney transplantation is the definitive, gold standard treatment that provides the best quality of life for end-stage renal disease patients. The treatment, however, is not accessible to many due to constraints such as blood type or human leukocyte antigen tissue type incompatibility between transplant candidates and their kidney donors. To overcome these incompatibilities, the transplant community has devised several novel schemes including KPD and desensitization. KPD allows patients with a willing - but incompatible - living donor to swap their incompatible donor with a more compatible donor, also in the KPD donor-patient pool, while the desensitization procedure removes antibodies from transplant recipients’ blood streams prior to surgery to reduce the risk of potential rejection of donated kidneys. Currently, both of these schemes have limitations. To overcome the limitations, prominent transplant experts have been advocating for combining the two schemes. This project aims to develop stochastic simulation and optimization-based algorithms for matching donors and recipients in a KPD system with desensitization therapy. In contrast to a conventional KPD system where transplant candidates simply swap their incompatible donors for more compatible donors in the system, the envisioned KPD systems would offer patients the additional option of undergoing a personalized desensitization therapy along with the option of swapping donors to significantly increase their likelihood of a match. The research objective is to develop an integrated dynamic stochastic simulation-optimization model comprised of: (i) an optimization strategy to identify the optimal personalized protocol for desensitization; (ii) improved robust/stochastic optimization methods to integrate the desensitization therapy into the KPD matching; and (iii) a decision-support tool to help patients decide whether to accept the desensitization regimen with a less compatible kidney, or wait for a more compatible one. The output of the integrated dynamic stochastic simulation-optimization model will include the suggested paired matchings from the combinatorial and simulation optimization algorithms, the realized matchings based on simulated patient behavior, and statistical estimates of key performance system metrics. In the last year of the project, the team will tailor the algorithms for the George Washington University Transplant Institute (GWTI) and Virginia Commonwealth University (VCU) Health Hume-Lee Transplant Center, which are interested in developing a joint local KPD exchange.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通过研究将D抗体去除方案纳入肾脏配对捐赠（KPD）系统的最佳生活质量，这将有助于改善肾脏移植的ta骨对肾脏移植。 - 肾脏疾病患者。目前，捐赠的肾脏都有限制或组合两个方案。不兼容的捐赠者在兼容的供体中，设想的KPD系统将为患者提供额外的个性化脱感疗法，以及Pppino RS的选择，以显着增加匹配的可能性。 （i最佳个性化协议的优化策略；组合和模拟优化算法衡量的患者行为，关键的统计估计在大学移植研究所（GWTI）和弗吉尼亚州联邦大学（VCU）健康休ume lee移植中心的统计估计中。该奖项反映了NSF'Stuterory任务，并在使用Foundation的知识分子优点和更广泛的审查标准的情况下支持DemeD支持TheValuon。