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

Extracellular volume (ECV) overload and endothelial cell dysfunction are mortality risk factors in hemodialysis (HD) patients. Endothelin-1 (ET-1), an endothelium-derived vasoconstrictive peptide, is associated with poor outcomes in HD patients. We hypothesized there would be associations between ET-1 and ECV overload in hypertensive HD patients.

We obtained pre-HD ET-1, ECV/weight (bioimpedance spectroscopy), pre-HD hemodynamics, and ambulatory blood pressure (BP) in an HD cohort. Following appropriate transformations, we conducted correlation and linear regression analyses idendifying associations between ET-1, ECV overload, 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, 3,161 (2,711-3,642) dynes × s/cm-5/m2, 2.92 (0.6) l/min/m2, and 143 (14) mm Hg, respectively. After reciprocal-transformation, ET-1 correlated with reciprocal-transformed ECV/weight (r = 0.3, P = 0.01), log-transformed TPRI (r = -0.3, P = 0.006), CI (r = 0.3, P = 0.009), and ambulatory BP (r = -0.3, P = 0.02). These associations persisted in linear regression analysis (β = 0.15, P = 0.002; β = -0.8, P = 0.002; β = 0.2, P = 0.002; β = -19, P = 0.03).

In hypertensive HD patients, ET-1 associates with ECV overload higher TPRI and ambulatory BP, and lower CI. 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.