Plasma Endothelin in Patients With End-Stage Renal Disease on Hemodialysis

Abstract

End-stage renal disease (ESRD) is a worldwide public health problem. The main treatment for ESRD is still hemodialysis (HD). Despite the substantial improvements in dialysis therapy, HD patients continue to experience significant mortality and morbidity.Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide implicated in the pathogenesis of hypertension, congestive heart failure, and inflammation, all of which are key pathophysiologic features of end-stage renal disease (ESRD). In hemodialysis patients, ET-1 increases strikingly but the association of ET-1 with adverse outcomes in individuals with end stage renal disease on hemodialysis is unclear. To test the hypothesis that increased ET-1 levels are associated with increased adverse events in hemodialysis patients, we measured plasma ET-1 levels in a cohort of 794 individuals with prevalent ESRD treated with maintenance hemodialysis. The primary outcomes were time to death and hospitalization. The median plasma ET-1 level was 2.02 (interquartile range, 1.57 – 2.71) pg/mL. Compared to individuals in the lowest quartile of plasma ET-1, those in the highest quartile had a 2.52-fold higher risk of death (HR 2.52, 95% CI 1.68 – 3.79) and a 1.13-fold increased risk of hospitalization (HR 1.16, 95% CI 1.04 – 1.23) in multivariable models adjusting for demographic, clinical, and laboratory variables.Higher plasma ET-1 appears to be associated with adverse events in hemodialysis patients independent of previously described risk factors. Future trials are expected to test the potential role for ET-1 antagonists as a pharmacological intervention in ESRD.