The kidney in advanced heart failure and durable mechanical circulatory support: phenotypes, prediction, and pathophysiology

项目摘要/摘要：本提案概述了要制定的5年指导培训计划 卡尔·瓦尔特，医学博士，医学硕士，贝勒医学院肾脏病医学助理教授， 独立的临床调查员。Walther博士是一名获得董事会认证的肾脏科医生，拥有 临床研究。他的研究重点是肾脏疾病和心脏病之间的关系，特别是 肾脏疾病在快速增长的持久机械循环支持领域的高负担(主要是 左心室辅助装置[LVADs])治疗晚期心力衰竭(HF)。这份提案包含了一个完整的 培训和研究计划，将Walther博士坚实的知识和经验基础转化为专业知识 在创新的研究方法和实践中，以改善LVAD受者和其他患者的肾脏疾病 晚期心力衰竭。职业目标是：1)培养先进/现代分析和统计知识 从密集的多维数据中获取有效、有用、个性化信息所需的技术；2) 发展生理学和前瞻性研究技术方面的专业知识，包括翻译生物标记物 科学，肾脏和心血管健康的个性化特征所必需的；3)经验 在多种疾病人群中领导一项前瞻性的、多专业的、协作的研究。集成的、 协作培训和研究计划包括正式课程、指导活动、会议和 有针对性的短期课程，将在贝勒和德克萨斯医疗队出色的环境中进行 中心。他将由具有广泛专业知识的高级导师和顾问组成的团队进行指导：高级分析 方法(Wolfgang Winkelmayer，MD，MPH，DSC和Jesse Schold，PhD)，翻译生物标记物科学 (史蒂文·可卡，DO，硕士)，前瞻性肾脏研究(Sankar Navaneethan医学博士，公共卫生硕士，硕士)，前瞻性 机械循环支持研究(Kenneth Liao，医学博士，博士)和肾脏功能成像(Emily 马里兰州张学良)。具体目标统一为准确了解和预测不利的肾脏后果 经久耐用的机械循环支持。AIM 1将在以下方面确定晚期心力衰竭的新全球表型 利用现有的国家数据库，出现严重不良肾脏后果的高风险。目标2将 前瞻性评估LVAD植入前肾实质健康状况(非侵入性测量， 使用一组肾脏生物标志物)与重要的肾脏结局相关。目标3将研究肾脏如何 长期机械循环支持过程中的实质健康变化及其与预后的关系 纵向肾实质健康与神经激素活化和炎症。这项研究是 在理解和预测持久机械循环影响的精确方法方面具有创新性 支持全球肾脏健康，这是减轻日益加重的心肾疾病负担的重要一步。

PROJECT SUMMARY/ABSTRACT: This proposal outlines a 5-year mentored training program to develop Carl Walther, MD, MS, Assistant Professor of Medicine-Nephrology at Baylor College of Medicine, into an independent clinical investigator. Dr. Walther is a board-certified nephrologist with a Master of Science in Clinical Research. His research focuses on the nexus of kidney disease and heart disease, in particular the high burden of kidney disease in the rapidly growing field of durable mechanical circulatory support (primarily left ventricular assist devices [LVADs]) for advanced heart failure (HF). This proposal contains an integrated training and research plan to build Dr. Walther’s strong foundation of knowledge and experience into expertise in innovative research methods and practice to improve kidney disease in LVAD recipients and others with advanced heart failure. The career goals are: 1) train in the advanced/modern analytic and statistical techniques necessary to obtain valid, useful, individualized information from dense, multidimensional data; 2) develop expertise in physiology and prospective research techniques, including translational biomarker science, necessary for individualized characterization of kidney and cardiovascular health; 3) experience leading a prospective, multispecialty, collaborative study in a multimorbid population. The integrated, collaborative training and research plan includes formal coursework, mentored activities, conferences and targeted short courses, and will be performed in the outstanding environment of Baylor and the Texas Medical Center. He will be guided by a team of senior mentors and consultants with broad expertise: advanced analytic methods (Wolfgang Winkelmayer, MD, MPH, DSc and Jesse Schold, PhD), translational biomarker science (Steven Coca, DO, MS), prospective kidney research (Sankar Navaneethan MD, MPH, MS), prospective mechanical circulatory support research (Kenneth Liao, MD, PhD), and functional kidney imaging (Emily Chang, MD). The specific aims unify to precisely understand and predict adverse kidney outcomes with durable mechanical circulatory support. Aim 1 will identify novel global phenotypes in advanced heart failure at high risk for important adverse kidney outcomes, leveraging an existing national database. Aim 2 will prospectively assess how kidney parenchymal health prior to LVAD implantation (measured non-invasively, using a panel of kidney biomarkers) is related to important kidney outcomes. Aim 3 will study how kidney parenchymal health changes during long-term mechanical circulatory support, and the relationship of longitudinal kidney parenchymal health with neurohormonal activation and inflammation. This research is innovative in its precise approach to understanding and predicting the effects of durable mechanical circulatory support on global kidney health, an essential step towards reducing the growing burden of cardiorenal disease.