Influence of Erythropoietin (EPO) in Regulation of Blood Pressure: A Systematic Review
Keywords:
erythropoietin; hypertension; erythropoiesis-stimulating agents; vascular regulation.Abstract
Background: Erythropoietin (EPO), a glycoprotein hormone best known for regulating erythropoiesis, has been implicated in blood pressure (BP) modulation. With widespread use of erythropoiesis-stimulating agents (ESAs) in chronic kidney disease (CKD) and oncology, concerns about hypertensive effects have intensified. Our objective is to systematically review PubMed literature from April 2020 to March 2025 on the influence of EPO (endogenous or exogenous) on blood pressure and hypertension risk.
Methods: We searched PubMed (April 2020–March 2025) using predefined terms. Out of 128 records, 22 duplicates were removed. After screening 106 abstracts, 87 were excluded. Full texts of 19 were assessed, and 10 were excluded (e.g., no BP data). Nine studies met eligibility criteria (4 human observational, 3 ESA intervention/clinical trials, 2 mechanistic/animal). Data were extracted and narratively synthesized.
Results: Observational studies demonstrated a positive association between endogenous plasma EPO levels and higher systolic BP, mean arterial pressure, and hypertension risk. Interventional studies showed ESA therapy in CKD patients increased hypertension incidence (OR ~2.17) and systolic BP by 3–6 mmHg. Mechanistic work revealed EPO-induced vascular changes mediated by nitric oxide inhibition, endothelin activation, sympathetic stimulation, and renin–angiotensin sensitivity.
Conclusions: Both endogenous and exogenous EPO contribute to BP elevation through non-erythropoietic vascular pathways. Careful BP monitoring is essential in ESA therapy, and future research should clarify dose thresholds, long-term cardiovascular outcomes, and mechanisms.
