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.

Public Health Relevance

Patients on thrice-weekly maintenance hemodialysis suffer from unacceptably high rates of cardiovascular morbidity and mortality. In particular significant low blood pressure events during hemodialysis are common and associate with adverse cardiac outcomes and death. This proposal aims to investigate mechanisms underlying these associations and to assess potential strategies to improve cardiac outcomes in chronic hemodialysis patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Rankin, Tracy L
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Brigham and Women's Hospital
United States
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Reeves, Patrick B; Mc Causland, Finnian R (2018) Mechanisms, Clinical Implications, and Treatment of Intradialytic Hypotension. Clin J Am Soc Nephrol 13:1297-1303
Flythe, Jennifer E; Mc Causland, Finnian R (2017) Dialysate Sodium: Rationale for Evolution over Time. Semin Dial 30:99-111
Opotowsky, Alexander R; Baraona, Fernando R; Mc Causland, Finnian R et al. (2017) Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation. Heart 103:434-442
Mc Causland, Finnian R; Claggett, Brian; Pfeffer, Marc A et al. (2017) Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease: Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial. Am J Nephrol 46:488-497
Singh, Anika T; Mc Causland, Finnian R (2017) Osmolality and blood pressure stability during hemodialysis. Semin Dial 30:509-517
Charytan, David M; Foley, Robert; McCullough, Peter A et al. (2016) Arrhythmia and Sudden Death in Hemodialysis Patients: Protocol and Baseline Characteristics of the Monitoring in Dialysis Study. Clin J Am Soc Nephrol 11:721-34
Mc Causland, Finnian R; Asafu-Adjei, Josephine; Betensky, Rebecca A et al. (2016) Comparison of Urine Output among Patients Treated with More Intensive Versus Less Intensive RRT: Results from the Acute Renal Failure Trial Network Study. Clin J Am Soc Nephrol 11:1335-42
Mc Causland, Finnian R; Claggett, Brian; Burdmann, Emmanuel A et al. (2016) C-Reactive Protein and Risk of ESRD: Results From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Am J Kidney Dis 68:873-881
Mc Causland, Finnian R; Waikar, Sushrut S (2015) Association of Predialysis Calculated Plasma Osmolarity With Intradialytic Blood Pressure Decline. Am J Kidney Dis 66:499-506
Mc Causland, Finnian R; Wright, John; Waikar, Sushrut S (2014) Association of serum sodium with morbidity and mortality in hospitalized patients undergoing major orthopedic surgery. J Hosp Med 9:297-302

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