权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Skeletal muscle dysfunction in persons with chronic kidney disease

慢性肾病患者的骨骼肌功能障碍

基本信息

批准号：
9310364
负责人：
Baback Roshanravan
金额：
$ 4.43万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2018-07-07
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9310364
关键词：
Adult Aerobic Exercise Area Award Biochemistry Biological Markers Cellular Stress Cessation of life Chronic Kidney Failure Clinical Clinical Research Clinical Trials Complication Data Data Collection Dialysis procedure Elderly Epidemiology Exercise Fatty acid glycerol esters Foundations Functional disorder Future Generations Goals High Prevalence Hospitalization Human Impairment Individual Insulin Resistance International Intervention Intervention Trial Investigation K-Series Research Career Programs Kidney Diseases Light Link Magnetic Resonance Spectroscopy Measurement Measures Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Metabolic Metabolism Methods Mitochondria Morbidity - disease rate Muscle Muscle Contraction Muscle function Nephrology Optics Organ Outcome Outcomes Research Oxidative Stress Oxygen Oxygen Consumption Patients Persons Phenotype Physical Function Physical Performance Physical activity Physiology Prospective cohort study Research Research Design Research Personnel Respiration Sentinel Series Skeletal Muscle Solid Spectrum Analysis Testing Time Training Translational Research Universities Washington cohort design disability disorder control epidemiology study experience experimental study frailty functional disability improved insulin sensitivity member metabolic imaging middle age mitochondrial dysfunction mortality multidisciplinary muscle form muscle metabolism novel patient oriented pilot trial programs prospective public health relevance sarcopenia strength training sugar tool translational study trial design

项目摘要

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Baback Roshanravan, senior nephrology clinical research fellow at the University of Washington. Dr. Roshanravan is establishing himself as a young investigator in patient- oriented clinical research focusing on the impact of chronic kidney disease (CKD) on skeletal muscle function. This award will provide him with training and mentored research experience in the following areas: (1) Translational study design investigating metabolic disturbances and functional impairments associated with skeletal muscle dysfunction in CKD; (2) Intervention trial design and longitudinal data collection; (3) Analysis and interpretation of magnetic resonance spectroscopy and optical spectroscopy (MRS/OS) measuring mitochondrial dysfunction in CKD; (4) Advanced training in physiology, metabolism, biochemistry adapted to the study of muscle dysfunction in CKD. To achieve these objectives he has assembled a team of mentors including his primary mentor Dr. Bryan Kestenbaum, nationally recognized biomarker researcher; and three co- mentors: Dr. Jonathan Himmelfarb, leader in translational and outcomes research in persons with kidney disease; Dr. Kevin Conley, internationally renowned expert in metabolic imaging; and Dr. Ian de Boer, expert in the field of metabolism in CKD. Skeletal muscle dysfunction (sarcopenia) is an under-recognized target organ complication of CKD with substantial adverse clinical consequences of disability, hospitalization, and death. Sarcopenia in this proposal is defined by impaired metabolism and physical function associated with decreased skeletal muscle mass or function. Skeletal muscle tissue relies on mitochondria to efficiently utilize oxygen to generate ATP. Impaired mitochondrial energetics is a central mechanism of sarcopenia in CKD. We propose a series of studies designed to shed light on the pathophysiology of sarcopenia in persons with CKD not treated with dialysis. First, we will measure skeletal muscle mitochondrial function using MRS/OS among members of an established cohort of patients with CKD. Second, we will test hypothesis that mitochondrial dysfunction in persons with CKD is associated with metabolic disturbances (oxidative stress and insulin resistance) and impaired physical function (physical performance, physical activity and fatigability). Third, we will conduc a pilot intervention trial of combined resistance training and aerobic exercise to assess changes in skeletal muscle mitochondrial function, metabolism and physical function. We hypothesize that exercise leads to improvements in mitochondrial function and physical function in persons with CKD. If successful, these experiments will identify novel pathophysiologic mechanisms for CKD associated sarcopenia. The proposed training will provide strong preliminary data and solid foundation in muscle metabolism and function to build upon as an independent investigator. Specifically, it will provide a basis for future investigation of prospective associations of mitochondrial function, physical function with clinical outcomes in CKD patients.