Inflammation, muscle wasting, and physical function in chronic kidney disease

慢性肾脏病中的炎症、肌肉萎缩和身体功能

• 批准号: 8876670
• 负责人: Matthew K Abramowitz
• 金额: $ 6.13万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8876670
• 关键词: Address; Affect; Age; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Biochemical; Biopsy; C-reactive protein; Cachexia; Caring; Catabolism; Cell physiology; Chronic; Chronic Kidney Failure; Clinical; Data; Development; Development Plans; Dialysis procedure; End stage renal failure; Epidemiology; Exercise Tolerance; Fostering; Future; Goals; Health; Homeostasis; Human; Individual; Inflammation; Interleukin-1; Interleukin-6; Kidney Diseases; Knowledge; Link; Literature; Measurement; Mentors; Mentorship; Metabolic; Metabolism; Methods; Molecular; Muscle; Muscle Proteins; Muscular Atrophy; Natural regeneration; Outcome; Pathology; Pathway interactions; Patient Care; Patients; Performance; Persons; Physical Function; Physiological; Physiology; Prevention; Proteins; Proteolysis; Recruitment Activity; Research; Research Methodology; Research Personnel; Research Proposals; Skeletal Muscle; Subgroup; Syndrome; System; TNF gene; Testing; Training; Ubiquitin; Uremia; career development; clinically relevant; cohort; disability; frailty; functional decline; functional disability; functional loss; functional status; improved; inflammatory marker; innovation; lean body mass; meetings; multicatalytic endopeptidase complex; muscle form; muscle metabolism; patient oriented; prevent; programs; prospective; protein degradation; satellite cell; sedentary; therapeutic target; vastus lateralis; wasting

DESCRIPTION (provided by applicant): The overall goal of this proposal is to foster the development of the candidate as an independent patient-oriented researcher focusing on skeletal muscle pathology associated with chronic kidney disease (CKD) and its functional and metabolic sequelae. The overarching aim of this proposal is to examine how inflammation affects changes in skeletal muscle physiology and physical function in the period surrounding dialysis initiation. The applicant will receive focused mentoring from experts in the study of CKD, muscle physiology, and metabolism and will combine epidemiological and molecular methods to address this question. This study will be the first to prospectively follow patients with advanced kidney disease in a pivotal moment of transition in their care: the initiation of dialysis. We will perform longitudinal measurements of markers of inflammation and important clinical and functional parameters. We will integrate these data with skeletal muscle physiology, and will simultaneously evaluate multiple homeostatic pathways in skeletal muscle in humans. Our aims are: (1) To define the association of inflammation with changes in skeletal muscle physiology, lean body mass, and physical function in patients with advanced predialysis CKD; and (2) To define the effect of the transition to chronic dialysis on inflammation, skeletal muscle homeostasis, lean body mass, and physical function. No studies in patients with CKD have simultaneously examined muscle wasting at a biochemical, physiologic, and clinical level as we propose. This application includes a rigorous 5 year career development plan that includes an integrated strategy of intensive mentorship, formal training in new research methods for studying human physiology, focused didactic coursework, and participation in research seminars and national scientific meetings. A significant portion of this plan is devoted to mastering new research methods that will enable the primary investigator to establish an independent research program at the intersection of kidney disease, muscle metabolism, and physical function. In summary, this proposal will produce important, clinically relevant data and is intended to generate preliminary data for an R01 application studying the effects of anti-inflammatory therapy on muscle wasting in patients with CKD. Intensive, focused, and interdisciplinary mentoring will foster the candidate's development as an investigator with expertise studying mechanisms of muscle atrophy in concert with clinical outcomes. This research proposal has the potential to improve the care of patients with CKD by leading to future innovations in the prevention and treatment of muscle wasting and functional decline.

描述（由申请人提供）：本提案的总体目标是促进候选人发展为独立的以患者为导向的研究人员，重点研究与慢性肾脏疾病（CKD）及其功能和代谢后遗症相关的骨骼肌病理学。本提案的首要目的是研究炎症如何影响透析开始前后骨骼肌生理学和身体功能的变化。申请人将接受CKD研究专家的重点指导， 肌肉生理学和代谢，并将结合联合收割机流行病学和分子方法来解决这个问题。这项研究将是第一个前瞻性随访晚期肾脏疾病患者的关键时刻，他们的护理过渡：开始透析。我们将 进行炎症标志物和重要临床和功能参数的纵向测量。我们将整合这些数据与骨骼肌生理学，并将同时评估多种稳态途径在骨骼肌在人类。我们的目标是：（1）确定炎症与晚期透析前CKD患者骨骼肌生理学、瘦体重和身体功能变化的相关性;（2）确定过渡到慢性透析对炎症、骨骼肌稳态、瘦体重和身体功能的影响。没有研究CKD患者同时检查肌肉萎缩在生化，生理和临床水平，因为我们建议。该应用程序包括一个严格的5年职业发展计划，其中包括密集的指导，研究人类生理学的新研究方法的正式培训，重点教学课程，以及参加研究研讨会和国家科学会议的综合战略。该计划的一个重要部分是致力于掌握新的研究方法，使主要研究者能够在肾脏疾病，肌肉代谢和身体功能的交叉点建立一个独立的研究计划。总之，该提案将产生重要的临床相关数据，并旨在为研究抗炎治疗对CKD患者肌肉萎缩影响的R 01申请产生初步数据。密集的，集中的和跨学科的指导将促进候选人的发展，作为一个具有专业知识的研究肌肉萎缩的机制与临床结果相一致的研究者。这项研究提案有可能通过在预防和治疗肌肉萎缩和功能下降方面的未来创新来改善CKD患者的护理。