Increased plasma levels of erythropoietin after renal denervation in patients with resistant hypertension

Erythropoietin (Epo) plays a crucial role in the formation and maturation of erythrocytes and is produced primarily by peritubular cells in the renal cortex. Previous studies suggest that renal sympathetic nerve activity (RSNA) may influence Epo regulation. Catheter-based renal denervation (RDN) has been shown to reduce renal noradrenaline spillover and blood pressure in patients with resistant hypertension. We therefore aimed to investigate whether RDN influences Epo levels. 33 patients with resistant hypertension (age 61 ± 12 y; baseline office blood pressure (BP) 165 ± 16/85 ± 18 mmHg despite treatment with an average of 4.9 ± 1.7 antihypertensive medications) underwent bilateral RDN. Plasma levels of Epo, office blood pressure, 24 h ambulatory blood pressure monitoring (ABPM), muscle sympathetic nerve activity (MSNA), renal function and haemoglobin were measured before the procedure and at 3 months follow-up. Antihypertensive medication was not changed during the first 3 months after RDN. Office blood pressure was reduced by 15 ± 19/5 ± 12 mmHg at 3 months after denervation (p < 0.001 for systolic BP; p = 0.033 for diastolic BP). 24h-mean systolic and diastolic BP were also reduced (from 145 ± 16 to 140 ± 18 mmHg; p = 0.036, and from 80 ± 11 to 77 ± 12 mmHg; p = 0.024), respectively. While haemoglobin levels remained unchanged, a significant increase in plasma Epo levels was observed at 3 months after RDN (7.81 ± 3.68 versus 9.88 ± 5.06 mIU/mL; p = 0.025). Changes in Epo levels correlated with baseline MSNA (r = 0.580, p = 0.004 for burst frequency; r = 0.471, p = 0.023 for burst incidence), such that the increase in Epo was most pronounced in patients with high baseline MSNA. The RDN-induced changes in MSNA tended to correlate inversely with changes in Epo levels (r = -0.402; p = 0.064). Our findings suggest that RDN is associated with increased plasma levels of Epo in the absence of changes in haemoglobin, and that these effects are possibly mediated via a reduction in sympathetic nerve activity.