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

项目摘要/摘要 这项提议的总体目标是促进候选人作为一名 独立的以患者为导向的研究人员，专注于与 慢性肾病(CKD)及其功能和代谢后遗症。最重要的目标 研究炎症如何影响骨骼肌生理学的变化。 以及开始透析前后的身体功能。申请者将收到 来自CKD、肌肉生理学和新陈代谢研究专家的重点指导 将结合流行病学和分子方法来解决这个问题。这项研究将是 第一个在关键时刻前瞻性跟踪晚期肾病患者的人 护理的过渡：开始透析。我们将进行纵向测量， 炎症标志物和重要的临床和功能参数。我们将整合 这些数据与骨骼肌生理学有关，并将同时评估多个 人体骨骼肌中的动态平衡通路。我们的目标是：(1)界定协会 炎症与骨骼肌生理、瘦体重和体力的变化 晚期透析前慢性肾脏病患者的功能；和(2)确定过渡的影响 慢性透析对炎症、骨骼肌内稳态、瘦体重和体力的影响 功能。在慢性肾脏病患者中，没有研究同时检查肌肉萎缩 我们建议的生化、生理和临床水平。此应用程序包括严格的5个 年职业发展计划，包括密集指导的综合战略， 正规培训用于研究人体生理学的新研究方法，重点讲授 课程作业，以及参加研究研讨会和国家科学会议。一个 该计划的很大一部分致力于掌握新的研究方法，使 首席研究员将在肾脏的交叉点建立独立的研究计划 疾病、肌肉新陈代谢和身体功能。总而言之，这项提案将产生 重要的临床相关数据，旨在为R01生成初步数据 抗炎治疗对慢性阻塞性肺疾病患者肌肉萎缩影响的应用研究 CKD。集中、集中和跨学科的指导将促进应聘者的发展 作为一名具有专业知识的研究人员，结合临床研究肌肉萎缩的机制 结果。这项研究建议有可能通过以下方式改善CKD患者的护理 引领未来在预防和治疗肌肉萎缩和功能性疾病方面的创新 拒绝。

Project Summary/Abstract 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.