Cardiac Complications of Hemodynamic Instability during Hemodialysis

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 DESCRIPTION (provided by applicant): This mentored career development award resubmission application will provide Dr. Finnian Mc Causland, MB, MMSc with the resources, additional training and protected time necessary to achieve his long-term goal of becoming an independent patient-oriented researcher. Dr. Mc Causland is an Instructor in Medicine at Harvard Medical School and an Associate Physician at Brigham and Women's Hospital. He has outlined a detailed training plan that includes didactic courses at Harvard School of Public Health, research conferences, leadership courses, training in the responsible conduct of research and presentations at international meetings during the award period. These will complement his strong mentoring plan, world-class advisory committee and build upon his prior training in human investigation for which he received a Masters in Medical Science degree. Approximately 400,000 patients in the United States are treated with life-sustaining hemodialysis (HD) for end stage renal disease (ESRD). These patients experience mortality rates of up to 20% per year, with up to one third experiencing significant hypotension during their regular hemodialysis treatments. This K23 Mentored Career Development Award resubmission proposal (PA- 14-049), entitled "Cardiac Complications of Hemodynamic Instability during Hemodialysis", aims to perform detailed examinations to critically investigate the role of intra-dialytic blood pressure decline with adverse cardiac outcomes. The ultimate goal of our research is to identify ways by which to reduce cardiovascular morbidity and mortality in chronic hemodialysis (HD) patients. In Aim 1, our collaborations with the Monitoring in Dialysis (MiD) study will facilitate sub-studies investigating associations of SBP decline with arrhythmia burden in chronic HD patients, via the novel use of implantable loop recorders. Aim 2 will involve creation of a prospective cohort study of patients initiating outpatient chronic HD. W will measure associations of greater intra-dialytic SBP decline with changes over time in biomarkers of myocardial injury and changes in left ventricular ejection fraction by cardiac MRI. In Aim 3 we will translate findings from our prior observational reports into a randomized controlled trial in hospitalized chronic HD patients. We will perform a single-blind, parallel grou randomized controlled trial of higher (142 mmol/L) vs. standard (138 mmol/L) dialysate sodium during hospitalization of 140 chronic HD patients, examining the magnitude of intra-dialytic SBP decline as the primary outcome. At the conclusion of this award period Dr. Mc Causland will have acquired the skills and expertise to successfully obtain R01 and/or R03 funding, thereby allowing him to continue his critically important research and to train future clinical investigatos.