Patterns and Implications of Functional Decline Among Kidney Transplant Candidates

 描述（由申请人提供）：肾移植（KT）的最新趋势表明，比以往任何时候都有更多的弱势患者等待接受肾移植，但移植提供者目前对KT候选人进行风险分层的工具或指导有限。也许因此，许多候选人可能会在等待名单上失去活性或死亡，而不是接受移植。器官的供应是有限的，KT的候选人在接受移植前往往必须等待数年。长期暴露于肾功能不良对患者健康有复杂的负面影响，包括慢性炎症和血管钙化，可能导致某些等待名单患者的健康急剧下降，从而导致KT率降低和KT后结局较差。该职业发展奖的目标是描述KT候选人健康下降的模式，并使用老化文献中的现有知识实施指标，以确定在等待KT期间经历加速健康下降的KT候选人。考虑到等待名单上健康状况的异质性，临床医生必须采取客观措施，捕捉健康下降的早期迹象，以便及时实施干预或替代KT策略，以改善患者的结局。该补助金的中心前提是，长期暴露于慢性肾脏疾病（CKD）和肾脏替代治疗导致许多KT候选人的健康状况加速下降，这一过程可以解释几个不良的等待名单结果，包括灭活候选人的比例增加。我提出了一系列的研究，以发现KT候选人的身体和认知功能下降的模式和可能解释这种下降的生物学过程，具体目标如下：1）发现身体和认知功能指标如何预测接受KT，失活，除名和死亡的CRIC研究中的晚期CKD患者; 2）前瞻性地将身体和认知功能的纵向度量实施到单个中心的事件KT候选人的移植评估中，以评估与非活动状态、除名和死亡的关联;以及3） 比较临床医生评估与客观的身体和认知指标对预测一个前瞻性队列的等待KT候选人中的移植相关不良结局的能力。我是一名临床讲师，目前由NIH F-32资助，拥有内科和肾脏学委员会认证以及宾夕法尼亚大学临床流行病学硕士学位。我还在宾夕法尼亚大学完成了美国移植协会认可的肾移植奖学金。这个NIDDK K-23职业发展奖将使我能够开发旨在优化脆弱的肾移植候选人的评估和护理的研究，目标是作为肾脏病学和肾移植领域的独立医生-科学家和国家领导者做出持续和持久的研究贡献。

 DESCRIPTION (provided by applicant): Recent trends in kidney transplantation (KT) indicate that more vulnerable patients are waiting to receive kidney transplants than ever before, but transplant providers currently have limited tools or guidance to risk-stratify KT candidates. Perhaps as a result, many candidates are likely to be inactivated or die on the waiting list instead of receiving a transplant. The supply of organs is limited, and candidates for KT must often wait for years before receiving a transplant. Prolonged exposure to poor kidney function has complex negative impacts on patient health, including chronic inflammation and vascular calcification, plausibly leading to steep rates of health decline in certain waitlisted patients tht result in lower rates of KT and inferior outcomes after KT. The goal of this career development award is to characterize patterns of health decline in KT candidates and implement metrics, using existing knowledge in the aging literature, to identify KT candidates who are experiencing accelerated health decline while awaiting KT. Given the heterogeneity of health status on the waitlist, it is imperative that clinicians have objective measures that capture early signs of healh decline so that timely interventions or alternative KT strategies can be implemented to improve patient outcomes. The central premise of this grant is that prolonged exposure to chronic kidney disease (CKD) and renal replacement therapy results in accelerated health decline in many KT candidates, a process that may explain several poor waitlist outcomes including the increasing proportion of inactivated candidates. I propose a series of studies to discover the patterns of decline in physical and cognitive function in KT candidates and the biologic processes that may explain this decline, with the following specific aims: 1) To discover how metrics of physical and cognitive function predict access to KT, inactivation, de-listing and death among individuals in the CRIC study with advanced CKD; 2) To prospectively implement longitudinal metrics of physical and cognitive function into the transplant evaluation of incident KT candidates at a single center in order to evaluate associations with inactive status, de-listing, and death; and 3) To compare clinician evaluation to objective physical and cognitive metrics on the ability to predict adverse transplant-related outcomes among a prospective cohort of waitlisted KT candidates. I am a clinical instructor currently funded by an NIH F-32 grant, with board certification in Internal Medicine and Nephrology and a Masters in Clinical Epidemiology from the University of Pennsylvania. I have also completed the American Transplant Society accredited kidney transplant fellowship at the University of Pennsylvania. This NIDDK K-23 Career Development Award will enable me to develop research aimed at optimizing the assessment and care of vulnerable kidney transplant candidates, with the goal of making ongoing and lasting research contributions as an independent physician-scientist and national leader in the fields of nephrology and kidney transplantation.