Refining repeat screening for coronary artery disease in kidney transplant candidates

7.项目总结 这项K23计划将为兴兴博士、医学博士和硕士提供受保护的时间、指导、培训和 研究经验，成为一名独立的临床调查员。郑博士是一名获得董事会认证的 肾病学家和认可的移植肾病学家，具有改善治疗效果的长期愿景 肾移植患者的医疗保健。她寻求将以病人为导向的研究和决策结合起来 科学为临床问题找到创新的解决方案。她将在这笔赠款中获得的技能，在指导下 一个强大的指导团队，包括1)整合以患者为中心的研究和决策分析模型； 2)评估不同患者亚群反应的异质性；3)高级建模技能。 这笔赠款建议完善慢性阻塞性肺疾病患者的冠状动脉疾病筛查程序。 肾脏疾病在等待肾移植的等待名单上。目前，患者接受重复心脏手术 每隔一段时间进行一次筛查测试，很少会导致干预。这些测试施加了很高的待遇 给患者带来负担，并可能推迟移植时间，同时给患者带来不清楚的好处。这 格兰特建议完善心脏筛查策略，并针对特定的患者亚群进行个性化(例如 老年糖尿病患者)。它将审查改变心脏测试频率和 心脏测试的风险分层基于一种简单、廉价和非侵入性的测试，可以 在常规临床环境下进行6分钟步行试验(6MWT)。该项目将通过以下方式实现这一广泛目标 三个具体目标：1)确定6MWT在识别没有额外心脏功能的低风险患者方面的特征 测试；2)模拟改变心脏测试频率和使用6 MWT的策略；3)设计 针对特定患者亚组的个性化策略，并在整个肾移植候选对象中进行建模 美国(US)的人口。前两个目标将来自于一群具有良好特征的患者 郑博士的机构。机器学习系统将被用来确定哪些患者亚组是最好的 服务于哪些策略(即响应的异质性)。第三个目标将利用美国的肾脏数据 程博士的导师和机构在利用该体系进行创新研究方面有着良好的记录。 这项拟议的工作有很高的潜力产生重大的临床影响。它的完成将使 冠状动脉疾病移植前筛查的合理策略的确定和表征 这可能会被纳入临床实践，或者为未来的多中心比较铺平道路 有效性试验。建议的工作在获奖期内是现实和可行的，并将允许郑博士 培养研究技能，促进和传播科学知识，创造更多的协作 网络，并竞争R01或同等资金。总而言之，K23奖项将为 让郑医生成为一名成功的独立临床研究员。

7. Project Summary This K23 proposal will provide Xingxing S. Cheng, MD, MS with the protected time, mentorship, training, and research experience to become an independent clinical investigator. Dr. Cheng is a board-certified nephrologist and accredited transplant nephrologist, with a long-term vision of improving the effectiveness of health care for kidney transplant patients. She seeks to combine patient-oriented research and decision science to find innovative solutions to clinical problems. Skills she will acquire in this grant, under the guidance of a strong mentorship team, include 1) integration of patient-oriented research and decision analytic models; 2) assessing the heterogeneity of response in different patient subgroups; and 3) advanced modelling skills. This grant proposes to refine the process of screening of coronary artery disease in patients with chronic kidney disease on the wait-list awaiting kidney transplantation. Currently, patients undergo repeat cardiac screening tests at frequent intervals, few of which result in interventions. These tests impose a high treatment burden on patients and potentially delay time to transplant, while bringing unclear benefit to the patient. This grant proposes to refine the cardiac screening strategy and personalize it for specific patient subgroups (e.g. elderly patients with diabetes mellitus). It will examine strategies that vary the frequency of cardiac testing and risk stratification for cardiac testing based on a simple, inexpensive, and non-invasive test that can be performed in routine clinical settings, a 6-minute walk test (6MWT). This project will achieve this broad aim by three specific aims: 1) to characterize the 6MWT in identifying low-risk patients who do not additional cardiac testing; 2) to model strategies varying the frequency of cardiac testing and use of 6MWT; 3) to design strategies personalized for specific patient subgroups and model them in the entire kidney transplant candidate population of the United States (US). The first two aims will arise from a well-characterized cohort of patients at Dr. Cheng’s institution. Machine-learning systems will be used to identify which patient subgroups are best served by which strategies (i.e. the heterogeneity of response). The third aim will leverage the US Renal Data System, which Dr. Cheng’s mentors and institution has a track record of leveraging for innovative research. The proposed work has high potential to make a significant clinical impact. Its completion will enable the identification and characterization of rational strategies for pre-transplant screening of coronary artery disease that may be incorporated into clinical practice or pave the way for a future multi-center comparative effectiveness trial. The proposed work is realistic and feasible within the award period, and will allow Dr. Cheng to build research skills, advance and disseminate scientific knowledge, create additional collaborative networks, and compete for R01 or equivalent funding. In summary, the K23 award will provide the support to enable Dr. Cheng to become a successful independent clinical investigator.