Prevalence and Impact of Frailty among Dialysis Patients

透析患者虚弱的患病率和影响

基本信息

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
项目类别：
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

项目摘要

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旧金山分校 (UCSF) 的医学教授，拥有以患者为导向的研究 (POR) 的悠久历史，重点是阐明患者身体功能障碍的程度患有慢性肾脏疾病，检查这种功能障碍的潜在机制，并测试改善该人群功能的策略。她的总体职业目标是扩大这一研究领域，成为该领域国际公认的研究者，并加强对 POR 感兴趣的初级研究者的指导。 UCSF 拥有丰富的 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，例如 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发展计划，以及支持肾病学实习生追求 POR 的肾病学 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对刚接受透析的患者虚弱的患病率和重要性的探索。虚弱是一个多维的概念，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、住院和死亡的风险增加。我们检查了 USRDS 透析发病率和死亡率研究 (DMMS) 第 2 波队列中的虚弱情况，发现发生 ESRD 患者的比例极高，包括许多非老年患者，符合虚弱标准，并且虚弱与更大的患病风险相关。随后住院并死亡。我们最近完成了一项新的 USRDS 特别研究——综合透析研究 (CDS) 的数据收集，其中 1,646 名透析患者完成了一份调查问卷，询问身体活动和功能以及与健康相关的生活质量，为我们提供了所需的数据根据体力活动少、身体机能差和疲劳/疲惫来定义虚弱表型。我们现在建议扩大对 ESRD 衰弱的研究，首先确定这个更现代的透析队列中衰弱的患病率，然后利用丰富的 CDS 数据更深入地研究与该人群衰弱相关的因素及其关系虚弱与 ESRD 过程相关事件和结果之间的关系。我们假设该队列中普遍存在虚弱，并且虚弱与住院和死亡率以及 ESRD 相关结局（例如血管通路类型和接受移植肾）独立相关。最后，我们假设虚弱与情绪低落、透析后疲劳和睡眠障碍有关，所有这些都会对这一人群的生活质量产生负面影响。希望这些分析能够更好地区分面临不良后果风险的透析患者。修订后的申请中添加了两个新项目，以解决虚弱表型的两个组成部分：肌肉萎缩/虚弱和缺乏身体活动。第一个项目将扩展 Johansen 博士最近的工作，评估氧化应激对肌肉疲劳的影响，以确定氧化应激标志物是否也与泛素蛋白酶体系统（肌肉分解代谢的主要途径）所涉及的蛋白质的表达相关。此外，作为 Johansen 博士的 R21 项目的一部分收集的肌肉样本也将有助于初步评估 N-乙酰半胱氨酸（一种抗氧化剂）的短期治疗是否与分解代谢蛋白表达减少有关。在第二个新项目中，Johansen 博士将扩展她之前测量 ESRD 患者身体活动的工作，将计步器用作评估工具和旨在增加该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 新病例数量不断增加以及相关的患者发病率和费用，慢性肾脏病被指定为《2010 年健康人群》的重点领域，其明确目标是“减少慢性肾病新病例”。肾脏疾病及其并发症、残疾、死亡和经济成本。”该项目旨在调查衰弱（ESRD 的主要并发症），以确定其增加死亡和住院风险（ESRD 费用的主要因素）的程度。该应用还将研究氧化应激作为导致虚弱的潜在因素，以及基于计步器的干预措施在增加身体活动、改善身体表现和内皮功能方面的潜力。这项工作的结果可能会导致进一步研究减少虚弱的策略，从而提高生活质量，并可能降低该人群的死亡率或住院率。