Prevalence and Impact of Frailty among Dialysis Patients

透析患者虚弱的患病率和影响

• 批准号: 7989266
• 负责人: KIRSTEN L. JOHANSEN
• 金额: $ 12.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989266
• 关键词: 1,25 (OH) vitamin D; Acetylcysteine; Activities of Daily Living; Acute myocardial infarction; Address; Adipose tissue; Admission activity; Aerobic Exercise; Affect; Age; Amputation; Anabolic Agents; Antioxidants; Appointment; Area; Attitude; Award; Behavior; Biopsy; Blood Vessels; Body Composition; Body Size; Body Weight; Body fat; Body mass index; Bone Diseases; California; Cardiac; Cardiovascular system; Caring; Catabolism; Cause of Death; Cessation of life; Characteristics; Chronic; Chronic Kidney Failure; Chronic Obstructive Airway Disease; Clinical; Clinical Research; Cohort Studies; Communities; Complication; Counseling; Cross-Sectional Studies; Data; Data Collection; Data Files; Depressed mood; Dialysis patients; Dialysis procedure; Dietary intake; Discrimination; Disease Management; Double-Blind Method; Early treatment; Educational Intervention; Educational Status; Elderly; End stage renal failure; Enrollment; Enteral; Environment; Event; Exercise; Exercise Tolerance; Exhibits; Fatigue; Fatty acid glycerol esters; Foundations; Functional disorder; Funding; General Population; Generations; Goals; Guidelines; Health; Health Personnel; Healthy People 2010; Height; Hematocrit procedure; Hemodialysis; Hip Fractures; Hospitalization; Hour; Hyperparathyroidism; Impairment; Individual; Institutes; Institutionalization; Insulin Resistance; Intervention; Intervention Studies; Investigation; Isometric Contraction; Joints; Kidney Diseases; Kidney Failure; Kidney Transplantation; Laboratories; Lead; Link; Lipids; Lipoproteins; Measures; Medical; Medicine; Mentors; Metabolic; Metabolism; Methods; Minerals; Modality; Moderate Exercise; Morbidity - disease rate; Muscle; Muscle Cells; Muscle Fatigue; Muscle function; Myopathy; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; Nursing Homes; Nutritional status; Obesity; Oral; Outcome; Oxidative Stress; Oxygen Consumption; Parathyroid Hormones; Parenteral Nutrition; Pathway interactions; Patient Participation; Patient Self-Report; Patients; Performance; Persons; Phenotype; Physical Function; Physical activity; Physical therapy; Physicians; Placebos; Plasma; Population; Prevalence; Prevention; Process; Program Development; Prospective Studies; Proteins; Protocols documentation; Quality of life; Questionnaires; Race; Randomized; Randomized Controlled Trials; Reactive Oxygen Species; Recommendation; Recording of previous events; Rehabilitation Centers; Rehabilitation therapy; Relative (related person); Reporting; Research; Research Design; Research Personnel; Research Project Grants; Research Support; Resources; Restless Legs Syndrome; Risk; Role; SECTM1 gene; Sampling; San Francisco; Secondary Hyperparathyroidism; Serum; Serum Albumin; Skeletal Muscle; Sleep disturbances; Smoking History; Staging; Starvation; Stroke; Supplementation; Surgeon; Survivors; System; Test Result; Testing; Thigh structure; Time; Tissues; Training; Training Programs; Translational Research; Ubiquitin; Universities; Update; Uremia; Vitamin D; Water; Weight; Work; adipokines; adverse outcome; alpha-Fetoproteins; analog; base; bone; bone metabolism; cardiovascular risk factor; career; cohort; control trial; cost; design; disability; economic cost; exhaustion; experience; follow-up; frailty; health related quality of life; human PTH protein; improved; improved functioning; indexing; inflammatory marker; interest; intervention effect; intervention program; meetings; mortality; multicatalytic endopeptidase complex; muscle form; muscle strength; neuronal cell body; nutrition; paricalcitol; patient oriented research; patient population; prevent; professor; programs; protective effect; protein expression; public health relevance; quadriceps muscle; randomized trial; response; sedentary; sex; therapy design; tool; treatment duration; treatment effect; waist circumference; wasting

DESCRIPTION (provided by applicant): Dr. Johansen was recently promoted to Professor of Medicine at the University of California, San Francisco (UCSF) with a long history of patient-oriented research (POR) focused on elucidating the degree of physical dysfunction among patients with chronic kidney disease, examining potential mechanisms for this dysfunction, and testing strategies to improve functioning in this population. Her overall career goals are to expand this line of research, becoming an internationally recognized investigator in this arena, and to increase her mentoring of junior investigators interested in POR. UCSF is a rich environment for training in POR, including an NIH-funded Clinical and Translational Sciences Institute (CTSI) offering a variety of opportunities, such as a K30-supported didactic training program in clinical research, a K12 (KL2) program, a Mentor Development program, which Dr. Johansen recently completed, as well as a Nephrology T32 that supports nephrology trainees in the pursuit of POR. This award would allow Dr. Johansen to reduce her clinical time in order to increase her POR and mentoring activities. The specific research to be supported under this award is an exploration of the prevalence and significance of frailty among patients new to dialysis. Frailty is a multidimensional construct reflecting a decline in health and functioning, initially observed in the elderly, that ultimately results in increased risk of disability, hospitalization, institutionalization, and death. We examined frailty in the USRDS Dialysis Morbidity and Mortality Study (DMMS) Wave 2 cohort and found that an extremely high proportion of incident ESRD patients, including many who were not elderly, met the criteria for frailty and that frailty was associated with greater risk of subsequent hospitalization and death. We recently completed data collection for a new USRDS special study, the Comprehensive Dialysis Study (CDS), in which 1,646 incident dialysis patients completed a questionnaire that asked about physical activity and functioning and health-related quality of life, providing the data needed for us to define a frailty phenotype based on low physical activity, poor physical functioning, and fatigue/exhaustion. We now propose to extend the investigation of frailty in ESRD by first determining the prevalence of frailty in this more modern dialysis cohort, then by capitalizing on the richness of the CDS data to delve deeper into the factors associated with frailty in this population and the relationship between frailty and ESRD process-related events and outcomes. We hypothesize that frailty is prevalent in this cohort and that frailty is independently associated with hospitalization and mortality as well as with ESRD-related outcomes such as type of vascular access and receipt of a transplanted kidney. Finally, we hypothesize that frailty is associated with depressed mood, post-dialysis fatigue, and sleep disturbance, all of which negatively affect quality of life in this population. It is hoped that these analyses will lead to better discrimination of dialysis patients at risk of adverse outcomes. Two new projects have been added to the revised application to address two of the components of the frailty phenotype: muscle wasting/weakness and physical inactivity. The first will extend Dr. Johansen's recent work evaluating the effects of oxidative stress on muscle fatigue to determine whether markers of oxidative stress are also associated with expression of proteins involved in the ubiquitin proteasome system, the major pathway of muscle catabolism. In addition, the muscle samples collected as part of Dr. Johansen's R21 project will also allow a preliminary assessment of whether short-term treatment with N-acetylcysteine, an anti-oxidant, is associated with reduced expression of catabolic proteins. In the second new project, Dr. Johansen will extend her previous work measuring physical activity in patients with ESRD to use pedometers as both an assessment tool and as a motivational tool in an intervention designed to increase physical activity in this population. PUBLIC HEALTH RELEVANCE: Because of the increasing number of new cases of ESRD in the US and the associated patient morbidity and costs, chronic kidney disease was designated as a focus area of Healthy People 2010, with the explicit goal to "reduce new cases of chronic kidney disease and its complications, disability, death, and economic costs." This project aims to investigate frailty, a major complication of ESRD, to determine the extent to which it increases the risk of death and hospitalization (a major contributor to the cost of ESRD). This application will also investigate oxidative stress as a potential contributor to frailty and the potential of a pedometer-based intervention to increase physical activity and improve physical performance and endothelial function. Results of this work may lead to further investigation of strategies to reduce frailty and thus increase quality of life and possibly reduce mortality or hospitalization in this population.

描述（由申请人提供）：Johansen博士最近晋升为加州大学弗朗西斯科分校（UCSF）的医学教授，具有长期的以患者为导向的研究（POR）历史，专注于阐明慢性肾脏疾病患者的身体功能障碍程度，检查这种功能障碍的潜在机制，并测试改善这一人群功能的策略。她的总体职业目标是扩大这一研究领域，成为这一竞技场中国际公认的研究人员，并增加对POR感兴趣的初级研究人员的指导。UCSF是一个丰富的POR培训环境，包括NIH资助的临床和转化科学研究所（CTSI），提供各种机会，如K30支持的临床研究教学培训计划，K12（KL 2）计划，导师开发计划，Johansen博士最近完成，以及支持肾脏学学员追求POR的肾脏学T32。该奖项将使Johansen博士能够减少她的临床时间，以增加她的POR和指导活动。该奖项支持的具体研究是探索新透析患者中虚弱的患病率和重要性。 虚弱是一个多层面的概念，反映了健康和功能的下降，最初在老年人中观察到，最终导致残疾，住院，机构化和死亡的风险增加。我们检查了USRDS透析发病率和死亡率研究（DMMS）第2波队列中的虚弱，发现极高比例的ESRD患者（包括许多非老年患者）符合虚弱标准，虚弱与后续住院和死亡的风险较高相关。我们最近完成了一项新的USRDS特殊研究（综合透析研究（CDS））的数据收集，其中1，646名事件透析患者完成了一份问卷，询问了身体活动和功能以及健康相关的生活质量，为我们提供了基于低体力活动，身体功能差和疲劳/疲惫定义虚弱表型所需的数据。我们现在建议扩展对ESRD虚弱的研究，首先确定这个更现代的透析队列中虚弱的患病率，然后利用CDS数据的丰富性，深入研究与该人群虚弱相关的因素以及虚弱与ESRD过程相关事件和结局之间的关系。我们假设虚弱在该队列中普遍存在，并且虚弱与住院和死亡率以及与ESRD相关结局（如血管通路类型和移植肾接受）独立相关。最后，我们假设虚弱与抑郁情绪、透析后疲劳和睡眠障碍有关，所有这些都会对该人群的生活质量产生负面影响。希望这些分析将导致更好地区分透析患者的不良结局风险。 修订后的应用程序中增加了两个新项目，以解决虚弱表型的两个组成部分：肌肉萎缩/虚弱和身体活动不足。第一个将扩展Johansen博士最近的工作，评估氧化应激对肌肉疲劳的影响，以确定氧化应激的标志物是否也与参与泛素蛋白酶体系统的蛋白质表达相关，泛素蛋白酶体系统是肌肉catalysis的主要途径。此外，作为Johansen博士的R21项目的一部分收集的肌肉样本也将允许初步评估使用N-乙酰半胱氨酸（一种抗氧化剂）进行短期治疗是否与分解代谢蛋白的表达减少有关。在第二个新项目中，Johansen博士将扩展她以前在ESRD患者中测量身体活动的工作，使用计步器作为评估工具和旨在增加这一人群身体活动的干预措施中的激励工具。 公共卫生相关性：由于美国ESRD新发病例数量的增加以及相关的患者发病率和成本，慢性肾脏疾病被指定为2010年健康人群的重点领域，其明确目标是“减少慢性肾脏疾病及其并发症、残疾、死亡和经济成本的新发病例。“该项目旨在调查ESRD的主要并发症虚弱，以确定其增加死亡和住院风险的程度（ESRD费用的主要贡献者）。本申请还将研究氧化应激作为脆弱的潜在贡献者，以及基于计步器的干预增加体力活动和改善身体表现和内皮功能的潜力。这项工作的结果可能会导致进一步调查的战略，以减少脆弱，从而提高生活质量，并可能减少死亡率或住院治疗的这一人群。