Neurovascular Mechanisms of Kidney Disease Progression in Older Adults

PROJECT SUMMARY The overall purpose of this K01 proposal is to provide the PI with the essential mentorship, career development, and research experience necessary to become an independent clinical and translational investigator in Geriatric Nephrology. The candidate’s long-term goal is to build an NIH-funded independent research program

investigating novel mechanisms and treatment targets to improve health outcomes in older patients with chronic kidney disease (CKD). To that end, the PI proposes a career development plan that will provide 1) new expertise in Geriatrics, autonomic physiology and imaging biomarkers as research tools; 2) scientific growth through a rigorous

training plan supported by a multidisciplinary mentoring team; and 3) didactic training in clinical research design and analysis through the Master of Science in Clinical Research (MSCR) offered by the Georgia Clinical and Translational Science Alliance (GA CTSA). The research training and project will leverage the vast

resources of Emory University, a world-class academic medical center with innovative scientific research laboratories and neighboring medical facilities that enable rapid translation of novel ideas. The goals of the proposed research project are to identify neural and vascular mechanisms contributing to accelerated

deterioration of kidney function in older patients with CKD. The prevalence and incidence of CKD are substantially higher in older adults, and elderly CKD patients have faster declines in kidney function that lead to increased risk of kidney failure, mortality, and poor quality of life. The central hypothesis is that older adults

with CKD have exaggerated renal hemodynamic reactivity to sympathetic activation, which in turn is associated with faster kidney function decline over time. To test this hypothesis, Aim 1 will determine if older patients with CKD have exaggerated reductions in renal blood flow, and impaired renal oxygenation that is

related to sympathetic nervous system over-activation. These studies will measure renal hemodynamics and sympathetic nerve activity using direct intraneural recordings of sympathetic nerve activity in vivo, and comprehensive imaging biomarkers to quantify changes in renal blood flow and oxygenation. In addition to the

mechanistic insights that will be examined in Aim 1, Aim 2 will use a longitudinal prospective study design to explore the potential impact of sympathetic overactivity on CKD progression, by exploring if heightened sympathetic activation and renal vasoconstriction are associated with faster rate of kidney function decline over

time in older CKD patients. The results from these studies will provide the foundation for a future NIH R01 grant that will include prospective studies to improve long-term kidney outcomes in older patients with CKD. This research project, combined with multidisciplinary mentorship, didactic education, and practical experience,

will provide Dr. Jeong with the training and skills to become a successful independent investigator.