Utility of virtual crossmatch in deceased donor kidney transplantation

虚拟交叉配血在已故供体肾移植中的应用

基本信息

批准号：
10180953
负责人：
Chethan Puttarajappa
金额：
$ 16.2万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10180953
关键词：
Acute Adoption Antibodies Antigens Attitude Award Blood Cells Clinical Clinical Research Communities Data Data Analyses Databases Decision Analysis End stage renal failure Epidemiology Future Goals Graft Rejection Graft Survival HLA Antigens Health Policy Health Services Health Services Research Health system Healthcare Histocompatibility Hospitalization Ischemia K-Series Research Career Programs Kidney Kidney Transplantation Longevity Master of Science Master&apos s Degree Mathematics Medical center Mentors Mentorship Morbidity - disease rate Observational Study Operative Surgical Procedures Organ Organ Procurements Organ Transplant Research Outcome Outcomes Research Patient-Focused Outcomes Patients Pattern Perception Policies Positioning Attribute Process Protocols documentation Publishing Quality-Adjusted Life Years Research Research Methodology Research Personnel Research Proposals Resources Risk Role Science Scientist Shipping Subgroup Survey Methodology Surveys System Techniques Time Transplant Surgeon Transplantation Transplantation Surgery United Network for Organ Sharing United States United States Centers for Medicare and Medicaid Services Universities Variant Waiting Lists base cost data sharing delayed graft function design experience human leukocyte antigen testing implantation improved indexing markov model mathematical model new technology organ allocation preference prevent prospective sensitizing antigen skills transplant centers virtual

项目摘要

PROJECT SUMMARY CANDIDATE: This proposal is for a K08 Mentored Clinical Scientist Research Career Development Award for Dr. Puttarajappa, a Transplant Nephrologist at the University of Pittsburgh Medical Center. He has completed a Master of Science in Clinical Research and aims to develop into a health services researcher with skills to apply observational data, mathematical modeling and decision analysis to kidney transplantation (KT). Under the mentorship of experts at the University of Pittsburgh, he will pursue courses in survey research, epidemiology, health policy and mathematical modeling in health care. These will allow him to complete his proposed research aims and facilitate transition to an independent investigator. Dr. Puttarajappa will be guided by experts in KT outcomes research (Dr. Hariharan), mathematical modeling and decision analysis (Drs. Kenneth Smith and Mark Roberts), and survey methodology and donor research (Dr. Howard Degenholtz). RESEARCH: Broadly, his aims are to investigate the Utility of Virtual Crossmatch (VXM) in deceased donor KT (DDKT). The 2014 kidney allocation system (KAS) gave high priority to highly sensitized (i.e. higher calculated PRA) waitlisted candidates and allowed for wider sharing of kidney donor profile index >85 kidneys, resulting in increased shipping of organs, higher non-local KT surgeries and increased cold ischemia time (CIT). To assess donor-recipient compatibility and avoid immediate transplant rejection, a physical cell-based crossmatch (XM) is routinely performed prior to KT. VXM is a technique that compares donor human leukocyte antigen(HLA) typing and recipient HLA antibody profile to predict physical XM results. VXM has the potential to decrease CIT in DDKT, which will reduce delayed graft function, rejection, and improve graft and patient survival. Reducing CIT could also reduce organ discard and improve organ utilization. Specific AIMS for this proposal are 1) Evaluate current crossmatch practices in deceased donor KT among different donor and recipient subgroups, along with assessing perceptions of transplant professionals regarding VXM, 2) Explore if use of VXM is associated with lower CIT and DGF, and if this is different before and after the introduction of KAS and, and 3) Explore if routine application of VXM prior to DDKT has the potential to improve patient outcomes. These aims will be achieved using a combination of surveys, analysis of data from the United Network of Organ Sharing, and mathematical modeling. His research will identify situations where a VXM will be sufficient to proceed to transplantation without a physical XM. Additionally, findings on national crossmatch practice variation and perceptions of the transplant community towards VXM will help direct future research, changes to histocompatibility protocols and health policy. This award will allow Dr. Puttarajappa to achieve the skills necessary to conduct independent clinical research in KT while simultaneously yielding valuable information on the optimization of crossmatch strategies for DDKT.

项目摘要候选人：该建议是为K08指导的临床科学家研究职业发展奖的候选人匹兹堡大学医学中心的移植肾脏科医生Puttarajappa博士。他已经完成临床研究科学硕士，旨在发展成具有技能的卫生服务研究人员将观察数据，数学建模和决策分析应用于肾脏移植（KT）。在下面匹兹堡大学专家的指导，他将攻读调查研究课程，医疗保健中的流行病学，健康政策和数学建模。这些将使他完成他的拟议的研究目标并促进过渡到独立研究者。 Puttarajappa博士将在KT成果研究专家（Hariharan博士）的指导下，数学建模和决策分析（肯尼斯·史密斯博士和马克·罗伯茨博士）以及调查方法和捐助者研究（霍华德博士 Degenholtz）。研究：广义上，他的目的是研究虚拟交叉匹配（VXM）的实用性已故的捐赠者KT（DDKT）。 2014年的肾脏分配系统（KAS）高度敏感（即较高计算的PRA）等待列表的候选人，并允许更广泛的肾脏捐赠者配置指数共享 > 85个肾脏，导致器官运输增加，非本地KT手术和寒冷增加缺血时间（CIT）。为了评估供体 - 接收者的兼容性并避免立即移植排斥反应，基于物理细胞的交叉匹配（XM）通常在KT之前执行。 VXM是一种比较的技术供体人白细胞抗原（HLA）打字和受体HLA抗体曲线以预测物理XM 结果。 VXM有可能减少DDKT中的CIT，这将减少延迟的移植功能，排斥，并改善移植物和患者生存。减少CIT还可以减少器官丢弃并改善器官利用率。该提案的具体目标是1）评估已故捐助者的当前交叉效果实践不同捐助者和接受者子组之间的KT，以及评估移植的看法有关VXM的专业人员，2）探索是否使用VXM是否与较低的CIT和DGF相关引入Kas之前和之后，以及3）探索是否在 DDKT有可能改善患者预后。这些目标将通过结合调查，来自器官共享网络的数据分析以及数学建模。他的研究将确定VXM足以在没有物理XM的情况下进行移植的情况。此外，关于国家交叉摩擦实践的发现和移植社区的看法迈向VXM将有助于指导未来的研究，组织相容性方案的变化和卫生政策。这奖项将使Puttarajappa博士能够实现在KT中进行独立临床研究所需的技能同时，同时提供了有关DDKT交叉匹配策略优化的有价值的信息。