Frailty and Adverse Health Outcomes of Aging in Older Adults with Kidney Failure

描述(由申请人提供)：美国有40万老年ESRD患者；55岁以上的成年人是增长最快的年龄段，也是最具挑战性的治疗和咨询群体。在老年终末期肾病患者中，接受两种可用治疗方式--透析和肾移植(KT)--的患者的风险预测是基于从国家登记中得出的通用指标，这些指标涵盖所有年龄的患者，并专注于一个二分的终点(生存/死亡)。这些结果可能与老年ESRD患者的相关性有限，他们面临着老年不良健康后果(AHOA)的高风险。在社区居住的老年人中开发的新的风险预测指标可能是唯一适合老年ESRD患者风险预测的方法。一个潜在的重要指标是虚弱，这是一种生理储备减少的独立综合征。全身性炎症被认为是由于对应激源的易感性增加而导致的虚弱和AHOA之间的联系。脆弱是 透析死亡率增加一倍，早期同种异体肾移植功能障碍增加一倍。然而，其他结果对老年ESRD患者也很重要。作为对透析和KT的反应，老年患者患AHOA(认知功能障碍、ADL残疾、抑郁和低生活质量)的风险很高。我们将在1个年长的队列中测试以下具体目标 (1)评估脆弱的轨迹和与脆弱下降相关的因素；(2)确定脆弱与AHOA的关联；(3)评估脆弱与AHOA之间的炎症途径。我们已经设计了一个导师计划，其中包括在老龄化研究方面的深入课程工作，并将在一个非常合适的环境中进行。导师团队包括老龄化研究、肾脏疾病研究和初级教职员工导师方面的专业知识。这个团队将帮助候选人实现她的职业目标：(1)扩大老龄研究方面的经验；(2)申请和获得R01补助金；以及(3)改善老年ESRD患者的治疗和结果。我们探索针对老年ESRD患者的新预测因素和结果，将通过提供风险预测信息、帮助指导临床决策，甚至可能提供对潜在生物过程的洞察，直接造福于这一人群及其提供者。

DESCRIPTION (provided by applicant): There are >400,000 older ESRD patients in the United States; adults over 55 are the fastest growing age group, and also the most challenging to treat and counsel. In older ESRD patients, risk prediction for patients undergoing the 2 available treatment modalities -- dialysis and kidney transplantation (KT) -- is based on generic metrics derived from national registries that cover patients of all ages and focus on one dichotomous endpoint (survival/death). These outcomes may be of limited relevance to older ESRD patients who are at high risk of adverse health outcomes of aging (AHOA). Novel risk prediction metrics developed in community-dwelling older adults may be uniquely suited to risk prediction among older ESRD patients. One potentially important metric is frailty, an independent syndrome of decreased physiologic reserve. Systemic inflammation is thought to mediate the association of frailty and AHOA due to increased vulnerability to stressors. Frailty is associated with doubling of dialysis mortality risk and a doubling of early KT allograft dysfunction. However, other outcomes are important for older ESRD patients. In response to dialysis and KT, older patients are at high risk for AHOA (cognitive dysfunction, ADL disability, depression, and low quality of life). We will test the following specific aims in 1 cohort of older dialysis initiates and 1 cohort of older KT recipients: (1) To estimate frailty trajectories and factors associated with frailty decline; (2) To determine the association of frailty and AHOA; and (3) To evaluate the inflammatory pathway between frailty to AHOA. We have designed a mentorship plan that includes in-depth course work in aging research and will be carried out in a well suited environment. The mentorship team includes expertise in aging research, kidney disease research, and mentorship of junior faculty. This team will help the candidate meet her career goals: (1) Widen experience in aging research; (2) Applying for and obtaining R01 grant funding; and (3) Improving treatment and outcomes of older ESRD patients. Our exploration of novel predictors and outcomes specific to older ESRD patients will directly benefit this population, and their providers, by informing risk prediction, helping guide clinical decision making, and possibly even providing insights into underlying biological processes.