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

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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.