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:9812059
- 负责人:
- 金额:$ 9.54万
- 依托单位:
- 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 2020-06-30
- 项目状态:已结题
- 来源:
- 关键词:
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.
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.
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Baback Roshanravan其他文献
Baback Roshanravan的其他文献
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{{ truncateString('Baback Roshanravan', 18)}}的其他基金
Impact of metabolic acidosis on muscle mitochondrial energetics, metabolic health and physical endurance in persons with chronic kidney disease
代谢性酸中毒对慢性肾病患者肌肉线粒体能量学、代谢健康和身体耐力的影响
- 批准号:
10278747 - 财政年份:2021
- 资助金额:
$ 9.54万 - 项目类别:
Impact of metabolic acidosis on muscle mitochondrial energetics, metabolic health and physical endurance in persons with chronic kidney disease
代谢性酸中毒对慢性肾病患者肌肉线粒体能量学、代谢健康和身体耐力的影响
- 批准号:
10671682 - 财政年份:2021
- 资助金额:
$ 9.54万 - 项目类别:
Impact of metabolic acidosis on muscle mitochondrial energetics, metabolic health and physical endurance in persons with chronic kidney disease
代谢性酸中毒对慢性肾病患者肌肉线粒体能量学、代谢健康和身体耐力的影响
- 批准号:
10471393 - 财政年份:2021
- 资助金额:
$ 9.54万 - 项目类别:
Skeletal muscle dysfunction in persons with chronic kidney disease
慢性肾病患者的骨骼肌功能障碍
- 批准号:
8706862 - 财政年份:2013
- 资助金额:
$ 9.54万 - 项目类别:
Skeletal muscle dysfunction in persons with chronic kidney disease
慢性肾病患者的骨骼肌功能障碍
- 批准号:
8568475 - 财政年份:2013
- 资助金额:
$ 9.54万 - 项目类别:
Skeletal muscle dysfunction in persons with chronic kidney disease
慢性肾病患者的骨骼肌功能障碍
- 批准号:
9310364 - 财政年份:2013
- 资助金额:
$ 9.54万 - 项目类别:
Skeletal muscle function and mitochondrial metabolism in non-diabetic CKD
非糖尿病 CKD 中的骨骼肌功能和线粒体代谢
- 批准号:
8310893 - 财政年份:2012
- 资助金额:
$ 9.54万 - 项目类别:
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