Endothelin-1 and Parameters of Systolic Blood Pressure in Hemodialysis

Abstract

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.