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：
8137282
负责人：
KIRSTEN L. JOHANSEN
金额：
$ 13.21万
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/8137282
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 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博士最近被晋升为加州大学旧金山分校（UCSF）的医学教授（UCSF），其长期以来，以患者为导向的研究（POR）的历史悠久，重点是阐明具有慢性肾脏疾病患者的物理功能障碍程度，从而为这种功能障碍的潜在机制中的潜在机制提供了这种功能障碍，以改善该策略，以改善该策略的策略。她的整体职业目标是扩大这一研究，成为该领域的国际认可的调查员，并增加对对POR感兴趣的初级调查员的指导。 UCSF是一个在POR中进行培训的丰富环境，包括NIH资助的临床和转化科学研究所（CTSI），提供各种机会，例如临床研究中的K30支持的教学培训计划，K12（KL2）计划（KL2）计划，Mentor Development，Mentor开发计划，Johansen Dr. Johansen Dosited of Newlology of Nephrology of Nephrology of Nephrology T322222222222222222222222222222年3月232年。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。根据该奖项支持的具体研究是对新透析患者的脆弱性和脆弱性的探索。脆弱是一种多维结构，反映了最初在老年人中观察到的健康和功能下降，最终导致残疾，住院，制度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波队列中的脆弱性，发现在内的ESRD患者（包括许多不是老年人）的出现的ESRD患者中，符合脆弱的标准，而这种脆弱的人与后来的住院和死亡的风险更大。我们最近完成了一项新的USRDS专科研究的数据收集，即全面的透析研究（CDS），其中1,646例透析患者完成了一份问卷调查，该调查表询问了有关体育锻炼以及与健康相关的生活质量的调查表，从而为我们提供了基于低身体活动的劣质表型所需的数据，并提供了较弱的身体活动，较差的身体功能，较差的身体功能，功能障碍，并且精疲力尽。现在，我们建议通过首先确定这种更现代的透析队列中的脆弱率来扩展ESRD中的脆弱性，然后通过利用CDS数据的丰富性来深入研究该人群中与脆弱的因素，以及与脆弱的因素以及与ESRD过程与ESRD相关的事件和与之相关的事件和成果。我们假设在这一队列中脆弱，并且脆弱与住院和死亡率以及与ESRD相关的结果（例如血管通道类型和接收移植肾脏）独立相关。最后，我们假设脆弱与情绪低落，透析后疲劳和睡眠障碍有关，所有这些都会对该人群的生活质量产生负面影响。希望这些分析能够更好地歧视透析患者，患有不良后果的风险。修订后的应用程序已添加了两个新项目，以解决脆弱表型的两个组成部分：肌肉浪费/无力和身体不活动。第一个将扩展约翰森博士最近的工作，以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的表达有关，这是肌肉分解代谢的主要途径。此外，作为约翰森（Johansen）R21项目的一部分收集的肌肉样本还将允许对抗氧化剂N-乙酰囊苷（一种抗氧化剂）的短期治疗是否与分解代谢蛋白的表达降低有关。在第二个新项目中，Johansen博士将扩展她以前的工作，以测量ESRD患者的体育活动，以使用计算机作为评估工具，也可以作为旨在增加该人群体育锻炼的干预措施的动机工具。公共卫生相关性：由于美国ESRD的新病例数量增加以及相关的患者发病率和成本，因此将慢性肾脏疾病指定为2010年健康人的重点领域，其明确的目标是“减少慢性肾脏疾病的新病例及其并发症，残疾，死亡，死亡和经济成本”。该项目旨在调查ESRD的脆弱，以确定增加死亡和住院风险的程度（ESRD成本的主要贡献者）。该应用还将研究氧化应激，以作为脆弱的潜在因素，以及基于计步器的干预措施增加体育活动并改善身体性能和内皮功能的潜力。这项工作的结果可能会导致对减少脆弱的策略进一步调查，从而提高生活质量，并可能降低该人群的死亡率或住院。