The purpose of this K23 Mentored Career Development Award proposal is to provide Jennifer E. Flythe, MD, MPH with the protected time and resources to allow her to pursue the additional training needed to reach her long-term goal of becoming an independent patient-oriented investigator. Dr. Flythe is a board-certified nephrologist at the University of North Carolina (UNC) at Chapel Hill. Her research focuses on fluid management among maintenance hemodialysis (HD) patients. Dialysis patients experience exceedingly high rates of cardiovascular complications that contribute to both poor health-related quality of life and high healthcare costs. Fluid-related factors are critical contributors to these adverse outcomes. Greater fluid gain between treatments obligates faster fluid removal (ultrafiltration, UF) during dialysis. Rapid UF rates are associated with intradialytic hypotension, chronic volume expansion due to reactive fluid boluses and failure to achieve target weight, and other adverse clinical outcomes. Innovative and patient-acceptable approaches to reducing UF-related harm are needed to improve outcomes. The support of the K23 Award will allow Dr Flythe to achieve the following objectives: 1) investigate the comparative cardiovascular risks of diuretic cessation (versus continuation) among patients initiating HD; 2) investigate the comparative effectiveness of UF profiling vs. conventional dialysis in reducing cardiovascular- related HD complications; 3) gain new epidemiology and clinical trials research skills; and 4) acquire expertise in cardiovascular outcomes. To accomplish these objectives, Dr. Flythe will investigate the comparative risks of diuretic cessation (vs. continuation) after HD initiation in a cohort of incident HD patients with histories of pre- dialysis diuretic use (Aim 1). Second, she will perform a crossover study of 30 maintenance HD patients with histories of elevated UF rates to investigate whether UF profiling vs. conventional HD reduces hypotension and cardiac ischemia (Aim 2). Additionally, she will complete formal coursework in advanced epidemiology and clinical trials and participate in targeted workshops and seminar series to broaden her comparative effectiveness research skillset. She will leverage a unique dialysis cohort of merged large dialysis organization and Medicare administrative claims data as well as UNC-owned outpatient dialysis facilities to accomplish these aims. The proposed work has high potential to make a significant clinical impact, as completion of the project aims will not only advance the current understanding of strategies to reduce UF-related harm but also provide preliminary data on strategies to target in future, larger trials. Importantly, the proposed work is realistic and feasible within the award period and will allow Dr. Flythe to build research skills, generate preliminary data, create collaborative relationships, and compete for R01 funding. Dr. Flythe will be closely guided by her co-primary mentors, M. Alan Brookhart, PhD, Professor of Epidemiology at the UNC Gillings School of Global Public Health, and Ronald J. Falk, MD, Professor of Medicine at the UNC School of Medicine. Doctors Brookhart and Falk?s complementary strengths in epidemiology and biostatistics (Brookhart) and national nephrology leadership (Falk) will be augmented by Dr. Flythe?s scientific advisory committee: 1) Alan Hinderliter, MD, Associate Professor of Medicine at UNC, cardiologist and echocardiography and cardiovascular outcomes expert; 2) Steven M. Brunelli, MD, MSCE, Vice President and Medical Director of Health Economics and Outcomes Research at DaVita Clinical Research and expert in dialysis outcomes research and HD hemodynamics; and 3) Laura Dember, MD, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine and dialysis clinical trial expert. Dr. Flythe will also draw upon the wealth of resources available in UNC?s research environment that include the UNC Schools of Medicine and Public Health, UNC Kidney Center, NC TraCS (home to UNC?s Clinical and Translational Science Award), Cecil G. Sheps Center for Health Services Research, and the UNC- owned Carolina dialysis units. Dr. Flythe?s proposed K23 research aims, mentorship team, career development plan, and collaborative research environment will catalyze her scientific productivity and provide her with the necessary skills and experience in epidemiology and clinical trials to become an independent investigator and future leader in dialysis research.

Public Health Relevance

Hemodialysis patients experience a high burden of cardiovascular complications that contribute to poor health- related quality of life and high mortality. Fluid-related factors such as fluid removal during dialysis (a process known as ultrafiltration) and chronic fluid overload contribute to these adverse outcomes. The current proposal aims to uncover drug therapies and dialysis treatment strategies that may improve these outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK109401-05
Application #
9959398
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2016-09-15
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Flythe, Jennifer E; Dorough, Adeline; Narendra, Julia H et al. (2018) Development and content validity of a hemodialysis symptom patient-reported outcome measure. Qual Life Res :
Flythe, Jennifer E; Hilliard, Tandrea; Castillo, Graciela et al. (2018) Symptom Prioritization among Adults Receiving In-Center Hemodialysis: A Mixed Methods Study. Clin J Am Soc Nephrol 13:735-745
Assimon, Magdalene M; Wang, Lily; Flythe, Jennifer E (2018) Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance Hemodialysis. J Am Soc Nephrol 29:2178-2188
Assimon, Magdalene M; Wang, Lily; Flythe, Jennifer E (2018) Intradialytic Hypertension Frequency and Short-Term Clinical Outcomes Among Individuals Receiving Maintenance Hemodialysis. Am J Hypertens 31:329-339
Assimon, Magdalene M; Brookhart, M Alan; Fine, Jason P et al. (2018) A Comparative Study of Carvedilol Versus Metoprolol Initiation and 1-Year Mortality Among Individuals Receiving Maintenance Hemodialysis. Am J Kidney Dis 72:337-348
Flythe, Jennifer E; Narendra, Julia H; Dorough, Adeline et al. (2018) Perspectives on Research Participation and Facilitation Among Dialysis Patients, Clinic Personnel, and Medical Providers: A Focus Group Study. Am J Kidney Dis 72:93-103
Flythe, Jennifer E; Assimon, Magdalene M; Overman, Robert A (2017) Target weight achievement and ultrafiltration rate thresholds: potential patient implications. BMC Nephrol 18:185
Flythe, Jennifer E; Assimon, Magdalene M; Wang, Lily (2017) Ultrafiltration Rate Scaling in Hemodialysis Patients. Semin Dial 30:282-283
Flythe, Jennifer E; Mc Causland, Finnian R (2017) Dialysate Sodium: Rationale for Evolution over Time. Semin Dial 30:99-111
Flythe, Jennifer E; Hilbert, Johnathan; Kshirsagar, Abhijit V et al. (2017) Psychosocial Factors and 30-Day Hospital Readmission among Individuals Receiving Maintenance Dialysis: A Prospective Study. Am J Nephrol 45:400-408

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