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脆弱患者等待接受肾移植，但移植提供者目前缺乏有限的工具或指导来对KT候选人进行风险分层。也许结果是，许多候选人可能会被灭活或死在等待名单上，而不是接受移植。器官的供应是有限的，KT的候选人往往必须等待数年才能接受移植。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，似乎会导致某些等待治疗的患者健康急剧下降，从而导致KT的发生率较低，KT后的预后较差。这个职业发展奖的目标是刻画KT候选人健康下降的模式，并利用老龄化文献中的现有知识来实施衡量标准，以确定在等待KT期间经历健康下降加速的KT候选人。鉴于候补名单上健康状况的异质性，临床医生必须有客观的措施来捕捉健康下降的早期迹象，以便能够实施及时的干预或替代的KT策略来改善患者的预后。这笔赠款的主要前提是，长期接触慢性肾脏疾病(CKD)和肾脏替代疗法会导致许多KT候选人健康状况加速下降，这一过程可能会解释几个糟糕的等待结果，包括失活候选人比例的增加。我提出了一系列研究，以发现KT候选人的身体和认知功能下降的模式以及可能解释这种下降的生物过程，具体目的如下：1)发现身体和认知功能的指标如何预测CRIC研究中患有晚期CKD的个人获得KT、失活、除名和死亡；2)前瞻性地将身体和认知功能的纵向指标应用到单一中心对发生KT的候选人的移植评估中，以评估与不活跃状态、除名和死亡的相关性；以及3) 比较临床医生的评估与客观的生理和认知指标预测等待名单上的KT候选患者中与移植相关的不良结局的能力。我是一名临床讲师，目前由美国国立卫生研究院F-32拨款资助，拥有内科和肾脏学委员会认证，并拥有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学会认可的肾移植奖学金。这项NIDDK K-23职业发展奖将使我能够开展旨在优化对脆弱的肾脏移植候选人的评估和护理的研究，目标是作为一名独立的内科科学家和肾脏移植领域的国家领导者，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.