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

• 批准号: 10614433
• 负责人: Chethan Puttarajappa
• 金额: $ 16.13万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10614433
• 关键词: 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; Mathematics; Medical center; Mentors; Mentorship; Modeling; 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 Assessment; 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; cost; data sharing; delayed graft function; design; experience; human leukocyte antigen testing; implantation; improved; indexing; mathematical model; new technology; organ allocation; preference; prevent; prospective; sensitizing antigen; skills; transplant centers; virtual

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。

项目成果

Author response to comments on economic analysis of subclinical rejection screening in kidney transplantation.

作者对肾移植亚临床排斥筛查的经济分析评论的回应。

• DOI: 10.1111/ajt.16356
• 发表时间: 2021
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Puttarajappa,ChethanM;Mehta,RajilB;Hariharan,Sundaram
• 通讯作者: Hariharan,Sundaram

Preoperative blood pressure and risk of delayed graft function in deceased donor kidney transplantation.

已故供体肾移植的术前血压和移植物功能延迟的风险。

• DOI: 10.1111/ctr.14776
• 发表时间: 2022
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Wazir,Shoaib;Abbas,Muhammad;Ratanasrimetha,Praveen;Zhang,Casey;Hariharan,Sundaram;Puttarajappa,ChethanM
• 通讯作者: Puttarajappa,ChethanM

Early Effect of the Circular Model of Kidney Allocation in the United States.

美国肾脏分配循环模型的早期效果。

• DOI: 10.1681/asn.2022040471
• 发表时间: 2023
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Puttarajappa,ChethanM;Hariharan,Sundaram;Zhang,Xingyu;Tevar,Amit;Mehta,Rajil;Gunabushanam,Vikraman;Sood,Puneet;Hoffman,William;Mohan,Sumit
• 通讯作者: Mohan,Sumit

Trends and impact on cold ischemia time and clinical outcomes using virtual crossmatch for deceased donor kidney transplantation in the United States.

• DOI: 10.1016/j.kint.2021.04.020
• 发表时间: 2021-09
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Puttarajappa CM;Jorgensen D;Yabes JG;Jeong K;Zeevi A;Lunz J;Tevar AD;Molinari M;Mohan S;Hariharan S
• 通讯作者: Hariharan S

Economic analysis of screening for subclinical rejection in kidney transplantation using protocol biopsies and noninvasive biomarkers.

• DOI: 10.1111/ajt.16150
• 发表时间: 2021-01
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Puttarajappa CM;Mehta RB;Roberts MS;Smith KJ;Hariharan S
• 通讯作者: Hariharan S