Short Daily versus Conventional Hemodialysis for Hypertensive Patients: A Randomized Cross-Over Study Deborah L. Zimmerman 1 *, Marcel Ruzicka 1 , Paul Hebert 2 , Dean Fergusson 3 , Rhian M. Touyz 4 , Kevin D. Burns 5 1 Associate Professor of Medicine, Division of Nephrology, Ottawa Hospital, Kidney Research Centre of the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada, 2 Professor of Medicine, Surgery, Anesthesia and Epidemiology, University of Ottawa; Senior Scientist, Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada, 3 Associate Professor, Departments of Medicine, Surgery, Epidemiology and Community Medicine, Senior Scientist and Director, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada, 4 Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom, 5 Professor of Medicine, Division of Nephrology, Senior Scientist, Kidney Research Centre of the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada Abstract Background: Treatment of end stage renal disease patients with short daily hemodialysis has been associated with an improvement in blood pressure. It is unclear from these studies if anti-hypertensive management had been optimized prior to starting short daily hemodialysis. Also, the potential mechanism(s) of blood pressure improvement remain to be fully elucidated. Study Design, Setting and Participants: We undertook a randomized cross-over trial in adult hypertensive patients with ESRD treated with conventional hemodialysis to determine: 1) if short-daily hemodialysis is associated with a reduction in systolic blood pressure after a 3-month blood pressure optimization period and; 2) the potential mechanism(s) of blood pressure reduction. Blood pressure was measured using Canadian Hypertension Education Program guidelines. Extracellular fluid volume (ECFV) was assessed with bioimpedance. Serum catecholamines were used to assess the sympathetic nervous system. Interleukin-6 (IL-6) and thiobarbituric acid reactive substances (T-BARS) were used as markers of inflammation and oxidative stress respectively. Results: After a 3-month run-in phase in which systolic blood pressure improved, there was no significant difference in pre- dialysis systolic pressure between short-daily and conventional hemodialysis (p = 0.39). However, similar blood pressures were achieved on fewer anti-hypertensive medications with short daily hemodialysis compared to conventional hemodialysis (p = 0.01). Short daily hemodialysis, compared to conventional hemodialysis, was not associated with a difference in dry weight or ECFV (p = 0.77). Sympathetic nervous system activity as assessed by plasma epinephrine (p = 1.0) and norepinephrine (p = 0.52) was also not different. Markers of inflammation (p = 0.42) and oxidative stress (p = 0.83) were also similar between the two treatment arms. Conclusions: Patients treated with short daily, compared to conventional hemodialysis, have similar blood pressure control on fewer anti-hypertensive medications. The mechanism(s) by which short daily hemodialysis allows for decreased anti- hypertensive medication use remains unclear but effects on sodium balance and changes in peripheral vascular resistance require further study. Trial Registration: ClinicalTrials.gov NCT00759967 Citation: Zimmerman DL, Ruzicka M, Hebert P, Fergusson D, Touyz RM, et al. (2014) Short Daily versus Conventional Hemodialysis for Hypertensive Patients: A Randomized Cross-Over Study. PLoS ONE 9(5): e97135. doi:10.1371/journal.pone.0097135 Editor: Dominique Guerrot, Rouen University Hospital, France Received September 3, 2013; Accepted April 14, 2014; Published May 29, 2014 Copyright: ß 2014 Zimmerman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was funded by the Ontario Heart and Stroke Foundation and the Ottawa Hospital Department of Medicine. The funders had no role in study design, data collection and analysis, decison to publish, or preparation of the manuscript. Competing Interests: The authors have declared no competing interests exist. * E-mail: dzimmerman@toh.on.ca Introduction More than 50% of the patients with end stage renal disease (ESRD) die from cardiovascular disease, a risk 10–20 times greater than the general population [1,2]. Of the potentially modifiable cardiovascular risk factors, greater than 80% of patients with ESRD have hypertension; 70% of whom are poorly controlled using conventional therapy [3]. An expanded extracellular fluid volume (ECFV) and an increase in peripheral vascular resistance (PVR) due to hemodynamic/trophic effects of increased sympa- thetic nerve activity and inflammation are frequently quoted mechanisms contributing to hypertension in ESRD [4]. Common to these processes is increased bioavailability of reactive oxygen species [5]. The intermittent nature of conventional hemodialysis treat- ments (4 hours, 3 days/week) results in the majority of patients PLOS ONE | www.plosone.org 1 May 2014 | Volume 9 | Issue 5 | e97135