Predictors and outcomes of frailty in dialysis patients

 描述（由申请人提供）：尽管虚弱通常被认为是一种老年综合征，但患有慢性疾病（包括慢性肾脏疾病（CKD））的个体存在过早虚弱的风险。许多接受血液透析的患者身体虚弱，包括相当大比例的65岁以下的患者。虚弱是由多个生理系统的累积下降引起的综合征，导致稳态储备受损和承受压力的能力下降。虚弱的操作定义各不相同，但已经出现了两种通用方法：赤字累积方法，其中将个体的损伤和状况相加以创建虚弱指数和身体虚弱表型，其特征在于一组组分，包括体重减轻，疲惫，低体力活动和不良的身体表现或自我报告的身体功能或其各种代理。虚弱与不良结局的较高风险相关，例如社区居住的老年人和接受维持性透析的患者的住院和死亡，其中虚弱的患病率甚至比一般老年人群高得多。 在透析人群中探索虚弱相关性的研究集中在虚弱表型方法上，并强调人口统计学和合并症，而不是潜在可改变的风险因素或病理生理学。具体而言，炎症、激素异常、体液超负荷、肌因子和多药治疗的潜在作用尚未得到充分研究，尽管它们具有补救的潜力。此外，虚弱通常被视为一种静止状态，研究在对虚弱进行单一基线评估后确定结果。更好地了解脆弱的发展，在某些情况下，解决方案可以更好地了解其预防和治疗。最后，对虚弱的不同定义或单个组成部分所提供的预后信息几乎没有比较 终末期肾病（ESRD）患者中的脆弱结构。本申请的目的是全面表征血液透析患者的虚弱-其起源和临床相关性、其轨迹以及与其发展和解决相关的因素。进行这些分析的基本原理是收集可用于预防或减轻虚弱及其后遗症的信息。我们建议利用在USRDS特殊研究队列中收集的数据，对储存的血清样本进行额外分析，并与USRDS中可用的结局信息联系起来，以实现以下特定目标：目标1：阐明血液透析患者身体虚弱的基础，并确定潜在的可补救相关因素。目标2：确定脆弱的轨迹，重点是脆弱的发展和解决的风险因素。目标3：确定虚弱预测不良结局的程度，包括死亡、住院、残疾发展、向更高水平护理的过渡、福尔斯和骨折。

 DESCRIPTION (provided by applicant): Although frailty is generally considered to be a geriatric syndrome, individuals with chronic diseases, including chronic kidney disease (CKD) are at risk for premature frailty. Many patients on hemodialysis are frail, including a sizeable proportion of those under age 65. Frailty is a syndrome resulting from cumulative declines in multiple physiologic systems, leading to impaired homeostatic reserve and decreased capacity to withstand stress. Operational definitions of frailty vary, but two general approaches have emerged: a deficit accumulation approach, in which an individual's impairments and conditions are summed to create a frailty index and a physical frailty phenotype characterized by a set of components that include weight loss, exhaustion, low physical activity, and poor physical performance or self-reported physical function or various proxies thereof. Frailty is associated with higher risk of adverse outcomes, such as hospitalization and death among community-dwelling elders and among patients receiving maintenance dialysis, in whom the prevalence of frailty is much higher than even the general elderly population. Studies exploring correlates of frailty in the dialysis population have focused on the frailty phenotype approach and have emphasized demographics and comorbidities rather than potentially modifiable risk factors or pathophysiology. Specifically, the potential contributions of inflammation, hormone abnormalities, fluid overload, myokines, and polypharmacy have been under-investigated despite their potential for remediation. In addition, frailty has generally been treated as a stati condition, with studies determining outcomes after a single baseline assessment of frailty. A better understanding of the development, and in some cases, resolution of frailty could lead to better insight into its prevention and treatment. Finally, there has been little comparison of the prognostic information afforded by different definitions of frailty or by the individual components of frailty constructs among patients with end-stage renal disease (ESRD). The objective of this application is to thoroughly characterize frailty among patients on hemodialysis - its origins and clinical correlates, its trajectory, and factors related to its development and resolution. The rationale for undertaking these analyses is to gather information that can be used to prevent or mitigate frailty and its sequelae. We propose to leverage the data collected in a USRDS special study cohort, additional analyses of stored serum samples, and linkage to outcome information available in the USRDS to accomplish the following specific aims: Aim 1: Elucidate the underpinnings of physical frailty among patients on hemodialysis and identify potentially remediable correlates. Aim 2: Determine trajectories of frailty, focusing on risk factors for development and resolution of frailty. Aim 3: Determine the extent to which frailty predicts adverse outcomes, including death, hospitalization, development of disability, transition to a higher level of care, falls, and fractures.