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

描述（由申请人提供）：美国有超过40万名老年ESRD患者; 55岁以上的成年人是增长最快的年龄组，也是治疗和咨询最具挑战性的年龄组。在老年ESRD患者中，接受2种可用治疗方式-透析和肾移植（KT）-的患者的风险预测基于来自国家登记的通用指标，这些指标涵盖所有年龄段的患者，并侧重于一个二分终点（生存/死亡）。这些结果可能与老年ESRD患者的相关性有限，老年ESRD患者具有老年不良健康结局（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患者的风险预测。一个潜在的重要指标是虚弱，一个独立的生理储备下降的综合征。全身性炎症被认为是介导脆弱性和AHOA的关联，因为对压力源的脆弱性增加。脆弱是 与透析死亡风险加倍和早期KT移植物功能障碍加倍相关。然而，其他结局对老年ESRD患者也很重要。作为对透析和KT的反应，老年患者发生AHOA（认知功能障碍、ADL残疾、抑郁和生活质量低下）的风险较高。我们将在1组老年人中测试以下特定目标 透析开始者和1个老年KT接受者队列：（1）估计虚弱轨迹和与虚弱下降相关的因素;（2）确定虚弱与AHOA的相关性;（3）评价虚弱与AHOA之间的炎症途径。我们设计了一个导师计划，其中包括在老龄化研究的深入课程工作，并将在一个非常适合的环境进行。导师团队包括衰老研究，肾脏疾病研究和初级教师导师的专业知识。该团队将帮助候选人实现她的职业目标：（1）扩大老龄化研究的经验;（2）申请并获得R 01赠款资金;（3）改善老年ESRD患者的治疗和结局。我们对老年ESRD患者特有的新预测因子和结局的探索将通过告知风险预测，帮助指导临床决策，甚至可能提供对潜在生物学过程的见解，直接使这一人群及其提供者受益。

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.