Anika T Singh1,2, Suraj Sarvode Mothi1,2, Ping Li3, Venkata Sabbisetti1,2, Sushrut S Waikar4, Finnian R Mc Causland1,2. 1. Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Harvard Medical School, Boston, Massachusetts, USA. 3. Department of Nephrology, State Key Laboratory of Kidney Disease, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital, Beijing, PR China. 4. Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston University, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Hypertension is common in hemodialysis (HD) patients. Increased blood pressure (BP) variability, particularly higher and lower extremes, is associated with adverse outcomes. We explored the association of endothelin-1 (ET-1), a potent vasoconstrictor, with different BP parameters (pre-HD, intra-HD, and post-HD) during HD in a contemporary patient cohort. METHODS: This study uses the DaVita Biorepository, a longitudinal prospective cohort study with quarterly collection of clinical data and biospecimens. Unadjusted and adjusted linear mixed effects regression models were fit to determine association of pre-HD ET-1 (log-transformed and quartiles) with HD-related systolic BP (SBP) parameters (pre-HD, nadir intra-HD, and post-HD). As ET-1 was measured at baseline, analyses were restricted to 1 year of follow-up. RESULTS: Among 769 participants, mean age was 52 years, 42% were females, and 41% were Black. Mean pre-HD SBP was 152 (±28) mm Hg and mean ET-1 concentration was 2.3 (±1.2) ng/ml. In fully adjusted models, each unit increase in SD of log-transformed ET-1 was associated with a 2.7 (95% confidence interval [CI] 1.5, 4.0) mm Hg higher pre-SBP; 1.6 (95% CI 0.9, 2.3) mm Hg higher nadir SBP; and 2.0 (95% CI 1.1, 2.9) mm Hg higher post-SBP. Each SD increase in log-transformed ET-1 was associated with 21% higher odds of experiencing intradialytic hypertension (odds ratio 1.21; 95% CI 1.10-1.34). CONCLUSIONS: Higher baseline ET-1 levels are independently associated with higher SBP and higher odds of intradialytic hypertension. These results highlight a potential role for ET-1 in BP control in HD patients and raise the possibility of ET-1 antagonism as a therapeutic target.
BACKGROUND: Hypertension is common in hemodialysis (HD) patients. Increased blood pressure (BP) variability, particularly higher and lower extremes, is associated with adverse outcomes. We explored the association of endothelin-1 (ET-1), a potent vasoconstrictor, with different BP parameters (pre-HD, intra-HD, and post-HD) during HD in a contemporary patient cohort. METHODS: This study uses the DaVita Biorepository, a longitudinal prospective cohort study with quarterly collection of clinical data and biospecimens. Unadjusted and adjusted linear mixed effects regression models were fit to determine association of pre-HD ET-1 (log-transformed and quartiles) with HD-related systolic BP (SBP) parameters (pre-HD, nadir intra-HD, and post-HD). As ET-1 was measured at baseline, analyses were restricted to 1 year of follow-up. RESULTS: Among 769 participants, mean age was 52 years, 42% were females, and 41% were Black. Mean pre-HD SBP was 152 (±28) mm Hg and mean ET-1 concentration was 2.3 (±1.2) ng/ml. In fully adjusted models, each unit increase in SD of log-transformed ET-1 was associated with a 2.7 (95% confidence interval [CI] 1.5, 4.0) mm Hg higher pre-SBP; 1.6 (95% CI 0.9, 2.3) mm Hg higher nadir SBP; and 2.0 (95% CI 1.1, 2.9) mm Hg higher post-SBP. Each SD increase in log-transformed ET-1 was associated with 21% higher odds of experiencing intradialytic hypertension (odds ratio 1.21; 95% CI 1.10-1.34). CONCLUSIONS: Higher baseline ET-1 levels are independently associated with higher SBP and higher odds of intradialytic hypertension. These results highlight a potential role for ET-1 in BP control in HD patients and raise the possibility of ET-1 antagonism as a therapeutic target.
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