Endothelin-1, Extracellular Volume Overload, and Hemodynamics in Hemodialysis Patients.

Abstract

Extracellular volume (ECV) overload and endothelial cell dysfunction (ECD) are independent risk factors for mortality in hemodialysis patients. Endothelin-1 (ET-1), an endothelium-derived vasoconstrictive peptide, is associated with poor outcomes in hemodialysis patients and heart failure patients without kidney disease. We hypothesized there would be associations between ET-1 and ECV overload assessed with bioimpedance spectroscopy (BIS) in hypertensive hemodialysis patients. We obtained pre-HD plasma ET-1, ECV/weight (using multi-frequency BIS), pre-HD hemodynamic measurements, and ambulatory blood pressure (BP) in a cohort of HD patients. Following appropriate transformations, we conducted correlation and linear regression analyses to identify associations between ET-1 and ECV overload. We further explored associations between ET-1 and total peripheral resistance index (TPRI), cardiac index (CI), and ambulatory BP. Among 66 patients, median ET-1 was 1.93 (1.49-2.56) pg/mL. Median pre-HD ECV/weight, median TPRI, mean CI, and mean systolic ambulatory BP were 0.25 (0.22-0.30) L/kg, 3161 (2711-3642) dynes*sec/cm-5/m2, 2.92 (0.6) L/min/m2, and 143 (14) mmHg, respectively. After reciprocal transformation, ET-1 correlated with reciprocal-transformed ECV/weight (r=0.3, p=.01), log-transformed TPRI (r=-0.3, p=.006), CI (r=0.3, p=.009) and ambulatory BP (r=-0.3, p=.02). Controlling for demographic variables, these associations persisted in linear regression analysis (β=0.15, p=.002; β=-0.8, p=.002; β=0.2, p=.002; β=-19, p=.03). In hypertensive HD patients, ECV overload is associated with ET-1. ET-1 is associated with higher TPRI and lower CI before dialysis and higher ambulatory BP. Further research is necessary to determine if ECV reduction lowers ET-1 or if pharmacologic ET-1 antagonism can improve outcomes in HD patients with refractory ECV overload.