Arterial Hypertension Induced by Erythropoietin and Erythropoiesis-Stimulating Agents (ESA)

Abstract

This review summarizes the evidence for a hypertensinogenic effect of Erythropoietin (Epo) in normal human subjects and predialysis, hemodialysis, and continuous ambulatory peritoneal dialysis (CAPD) patients. The possible mechanisms of Epo-induced hypertension are examined with in vivo animal and in vitro data, as well as pathophysiological human studies in both normal subjects and CKD patients. The evidence for a hypertensinogenic effect of erythropoiesis-stimulating agents (ESAs) in normal subjects, predialysis CKD, hemodialysis, and CAPD patients is compelling. Epo increases BP directly and notably independently of its erythropoietic effect and its effect on blood rheology. The potential for the development of future agents that might act as specific stimulators of erythropoiesis, devoid of direct hemodynamic side effects is underscored.

Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD

“…In contrast to the hypertensive risks of ESAs, no SAEs of hypertension were reported in this study. The reported rate of hypertensive AEs (7.6% of treated patients) was below what has been reported for similar patient populations treated with ESAs (16%-32%) (35,36) and comparable with placebo rates seen in other similar studies in this patient population (37). A recent CKD patient cohort study estimated 7.7 deaths and 8.0 progression to dialysis initiation events per 100 patient-years for those with stage 4 CKD and 41.4 deaths and 9.4 progression to dialysis initiation events per 100 patientyears for those with stage 5 CKD (38).…”

Naturally Occurring Higher Hemoglobin Concentration Does Not Increase Mortality among Hemodialysis Patients

“…Inflammation would also be expected to contribute to lower hemoglobin concentrations, which likely explains the relationships between serum albumin concentration, serum ferritin concentration, and catheter hemoaccess with Endogenous EPO status. ESA administration may cause increases in BP, 8 and this may explain the higher likelihood of hypertension among the Other group [although it does not explain the higher likelihood of hypertension as the cause of ESRD among the Other group]. Cardiovascular and lung diseases were associated with increased likelihoods of Endogenous EPO status.…”

Hypertension in Pediatric Long-term Hemodialysis Patients in the United States

“…However, because the hypertensive patients were more anemic than normotensive patients on similar erythropoiesis-stimulating agent doses, they could be considered more erythropoietin resistant. Erythropoietin-stimulating agents are known to increase BP in a dose-dependent manner and appear to have the strongest hypertensive effect on hemodialysis patients (29). The mechanisms by which erythropoietin-stimulating agents induce hypertension were recently reviewed; these include increased mean arterial BP that is erythropoietin specific and independent of erythropoietin-induced changes in red cell mass or viscosity, enhanced sensitivity to norepinephrine and angiotensin II, and increased circulating levels of endothelin-1 and impaired endothelial relaxation (29).…”