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

晚期心力衰竭中的肾脏和持久机械循环支持：表型、预测和病理生理学

• 批准号: 10417108
• 负责人: Carl Walther
• 金额: $ 18.38万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10417108
• 关键词: Acute; Affect; Anatomy; Animals; Area; Bayesian Analysis; Biological; Biological Markers; Cardiac Output; Cardiac Surgery procedures; Central venous pressure; Cessation of life; Characteristics; Chronic; Clinical; Clinical Data; Clinical Investigator; Clinical Research; Cluster Analysis; Coca; Complex; Creatinine; Databases; Dialysis procedure; Dimensions; Disease; Doctor of Philosophy; Environment; Event; Factor Analysis; Fibrosis; Filtration; Foundations; Functional disorder; Goals; Health; Heart; Heart Diseases; Heart Transplantation; Heart failure; Hour; Individual; Inflammation; Injury; Ischemia; Kidney; Kidney Diseases; Kidney Transplantation; Knowledge; Length; Master of Science; Measurement; Measures; Medical center; Medicine; Mentors; Modernization; Multicenter Trials; Nephrology; Niacinamide; Non-Insulin-Dependent Diabetes Mellitus; Oral; Outcome; Patients; Perioperative; Persons; Phenotype; Physiology; Population; Process; Quality of life; Refractory; Renal function; Research; Research Methodology; Research Support; Research Technics; Risk; Science; Sepsis; Serum; Severities; Syndrome; Techniques; Texas; Time; Training; Training Programs; Tubular formation; Uncertainty; Variant; advanced analytics; analytical method; biomarker panel; blood pressure control; cardiovascular health; career; cohort; college; experience; functional improvement; heart function; high risk; implantation; improved; inflammatory marker; innovation; insight; interstitial; kidney dysfunction; kidney imaging; left ventricular assist device; mechanical circulatory support; multidimensional data; multiple chronic conditions; novel; precision medicine; predictive modeling; professor; prospective; randomized trial; renal damage; repaired; symposium; systemic inflammatory response

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.

项目摘要/摘要：该提案概述了一个为期 5 年的指导培训计划，以开发 Carl Walther，医学博士、理学硕士，贝勒医学院医学肾病学助理教授， 独立的临床研究者。 Walther 博士是一位经过委员会认证的肾脏病专家，拥有以下学科的理学硕士学位： 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））用于治疗晚期心力衰竭（HF）。该提案包含一个综合的 培训和研究计划，将瓦尔特博士坚实的知识和经验基础转化为专业知识 致力于改善 LVAD 接受者和其他患有肾病的人的肾脏疾病的创新研究方法和实践 晚期心力衰竭。职业目标是：1）接受高级/现代分析和统计培训 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，包括转化生物标志物 科学，对于肾脏和心血管健康的个性化表征是必要的； 3）经验 领导一项针对多病人群的前瞻性、多专业合作研究。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，将在贝勒大学和德克萨斯医学院的优良环境中进行 中心。他将受到一支由具有广泛专业知识的高级导师和顾问组成的团队的指导：高级分析 方法（Wolfgang Winkelmayer，医学博士、公共卫生硕士、理学硕士和 Jesse Schold 博士）、转化生物标记科学 （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，医学博士、博士）和功能性肾脏成像（Emily 张，医学博士）。具体目标是准确理解和预测肾脏不良后果 耐用的机械循环支持。目标 1 将确定晚期心力衰竭的新的整体表型 利用现有的国家数据库，出现重要的肾脏不良后果的高风险。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）与重要的肾脏结果相关。目标 3 将研究肾脏如何 长期机械循环支持期间实质健康的变化以及 纵向肾实质健康与神经激素激活和炎症。这项研究是 其创新在于其精确的方法来理解和预测持久机械循环的影响 支持全球肾脏健康，这是减轻日益严重的心肾疾病负担的重要一步。