Prevalence and Impact of Frailty among Dialysis Patients

透析患者虚弱的患病率和影响

• 批准号: 8326749
• 负责人: KIRSTEN L. JOHANSEN
• 金额: $ 13.12万
• 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/8326749
• 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; Clinical Sciences; 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 Nutrition; 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; Hormones; 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 gland; 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; United States National Institutes of Health; 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; improved; improved functioning; indexing; inflammatory marker; instrumental activity of daily living; interest; intervention effect; 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; 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.

描述(申请人提供)：Johansen博士最近被提升为加州大学旧金山分校(UCSF)的医学教授，长期从事以患者为中心的研究(POR)，专注于阐明慢性肾脏疾病患者身体功能障碍的程度，研究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，成为这一领域的国际公认的调查员，并增加对POR感兴趣的初级调查人员的指导。加州大学旧金山分校提供丰富的POR培训环境，包括由美国国立卫生研究院资助的临床与翻译科学研究所(CTSI)，提供各种机会，如K30支持的临床研究教学培训计划、K12(KL2)计划、Johansen博士最近完成的导师培养计划，以及支持肾病实习生追求POR的T32计划。这项奖励将允许Johansen博士减少她的临床时间，以增加她的POR和指导活动。在该奖项下支持的具体研究是探索脆弱在新入行透析的患者中的流行率和意义。 脆弱是一个多维结构，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、住院和死亡风险增加。我们在USRDS透析发病率和死亡率研究(DMMS)第2波队列中检查了虚弱，发现极高比例的事件ESRD患者，包括许多非老年患者，符合虚弱的标准，并且虚弱与随后住院和死亡的更大风险相关。我们最近完成了一项新的USRDS特别研究的数据收集，即全面透析研究(CDS)，其中1,646名透析患者完成了一份问卷，询问体力活动和功能以及与健康相关的生活质量，为我们定义基于低体力活动、身体功能不良和疲劳/疲惫的虚弱表型提供了所需的数据。我们现在建议扩展对ESRD脆弱性的调查，首先确定在这一更现代的透析队列中脆弱的流行率，然后利用CDS数据的丰富性来更深入地研究这一人群中与脆弱性相关的因素，以及脆弱性与ESRD过程相关事件和结果之间的关系。我们假设虚弱在这一队列中普遍存在，并且虚弱与住院和死亡率以及与ESRD相关的结果(如血管通路类型和接受移植肾脏)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有不良后果风险的透析患者。 修订后的申请增加了两个新项目，以解决虚弱表型的两个组成部分：肌肉萎缩/虚弱和缺乏体力活动。第一项研究将扩展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泛素蛋白酶体系统中涉及的蛋白质的表达有关，泛素蛋白酶体系统是肌肉分解代谢的主要途径。此外，作为Johansen博士R21项目的一部分收集的肌肉样本还将提供初步评估，以确定抗氧化剂N-乙酰半胱氨酸的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博士将扩展她之前测量ESRD患者体力活动的工作，将计步器用作评估工具和激励工具，旨在增加ESRD患者的体力活动。