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

项目概要/摘要：本提案概述了一项为期5年的指导培训计划， 贝勒医学院医学-肾脏学助理教授Carl Walther，医学博士，理学硕士， 独立临床研究者。Walther博士是一位委员会认证的肾病学家，拥有理学硕士学位， 临床研究。他的研究重点是肾脏疾病和心脏病的关系，特别是 在快速发展的持久机械循环支持领域（主要是 左心室辅助装置[LVAD]）用于晚期心力衰竭（HF）。该提案包含一个综合 培训和研究计划，以建立沃尔特博士的知识和经验的坚实基础，成为专业知识 在创新的研究方法和实践中，以改善LVAD接受者和其他患有 晚期心力衰竭职业目标是：1）培养先进/现代分析和统计 从密集的多维数据中获取有效的、有用的、个性化的信息所必需的技术; 2） 发展生理学和前瞻性研究技术方面的专业知识，包括翻译生物标志物 科学，肾脏和心血管健康的个性化表征所必需的; 3）经验 领导一项在多病人群中进行的前瞻性、多专业、协作研究。一体化， 合作培训和研究计划包括正式的课程，指导活动，会议和 有针对性的短期课程，并将在贝勒和得克萨斯州医疗的杰出环境中进行 中心他将由一个具有广泛专业知识的高级导师和顾问团队指导：高级分析 方法（Wolfgang Winkelmayer，MD，MPH，DSc和Jesse Schold，PhD），转化生物标志物科学 （Steven Coca，DO，MS），前瞻性肾脏研究（Sankar Navaneethan MD，MPH，MS），前瞻性 机械循环支持研究（Kenneth Liao，MD，PhD）和功能性肾成像（艾米丽 Chang，MD）。具体目标统一为精确理解和预测不良肾脏结局， 持久的机械循环支持。Aim 1将在晚期心力衰竭中识别新的整体表型， 重要肾脏不良结局的高风险，利用现有的国家数据库。目标2将 前瞻性地评估LVAD植入前肾实质健康如何（非侵入性地测量， 使用一组肾脏生物标志物）与重要的肾脏结果有关。目的3将研究肾如何 长期机械循环支持期间实质健康变化，以及 纵向肾实质健康与神经激素激活和炎症。本研究是 创新的精确方法来理解和预测持久的机械循环的影响， 支持全球肾脏健康，这是减少心肾疾病日益增长的负担的重要一步。

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.