Renal denervation (RDN) is associated with decreased plasma renin activity (PRA) and aldosterone levels in patients with hypertension, according to a recent study.

RDN is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce blood pressure (BP), noted study authors Felix Mahfoud, MD, of Saarland University Hospital in Homburg/Saar, Germany, and colleagues.

In a study of patients with hypertension who were not taking antihypertensive medications, RDN was significantly associated with decreased PRA and aldosterone levels at 3 months compared a control group of patients who received a sham procedure.

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The study included 331 patients who participated in the SPYRAL HTNOFF MED Pivotal trial: 166 in the RDN group and 165 in the control arm. At baseline, the intervention and control groups had similar PRA values (1.0 and 1.1 ng/mL/h, respectively). At 3 months, the change in PRA from baseline was significantly greater for the RDN than control group (-0.2 vs 0.1 ng/mL/h), Dr Mahfoud’s team reported in the Journal of the American College of Cardiology. The RDN-treated patients also experienced a significantly greater reduction in aldosterone level at 3 months compared with the control arm (-1.2 vs 0.4 ng/mL).

The investigators compared the effect of RDN in patients with a baseline PRA of 0.65 ng/mL/h or higher and those with a PRA less than 0.65 ng/mL/h. Office and ambulatory BP measurements were similar for patients in both groups at baseline. The effect of RDN was stronger in the group with a baseline PRA of 0.65 ng/mL/h or higher. In this group, the 24-hour systolic BP (SBP) at 3 months had decreased by 7.1 mm Hg in the RDN-treated patients compared with a decrease of 1.1 mm Hg in the control arm, a significant difference between the groups. Among patients with PRA less than 0.65 ng/mL/h, both study arms had smaller decreases in PRA (-1.5 and -0.7 mm Hg in the RDN and control groups, respectively), and the between-group difference was not significant.

The effect of RDN on office SBP also was more pronounced in the patients with a baseline PRA of 0.65 ng/mL/h or higher. At 3 months, RDN-treated patients had a 12.8 mm Hg reduction in office SBP, whereas those in the control arm had a 2.9 mm Hg reduction, a significant difference between the groups. In the patients with lower PRA, the reductions were 7.1 and 3.7 mm Hg, respectively, a nonsignificant difference.

Dr Mahfoud and colleagues pointed out that they observed reductions in office SBP according to baseline PRA at 2 weeks post-procedure, indicating that RDN impacts renal physiology as early as 2 weeks after treatment.

In an accompanying editorial, Franz H. Messerli, MD, of the Swiss Cardiovascular Center at the University of Bern in Switzerland, and coauthors observed, “It has been more than a decade since RDN was first used to treat hypertension and hundreds of million dollars have been spent on researching this issue. To our way of thinking the results are sobering. Clearly, the paper of Mahfoud et al. is one more solid pebble in the mosaic assessing the antihypertensive mechanism of RDN and also attesting to its similarity to beta-blockade.”

Disclosures: The SPYRAL HTN-OFF MED Pivotal trial was sponsored by Medtronic. Please see the original references for a full list of authors’ disclosures.


Mahfoud F, Townsend RR, Kandzari DE, et al. Changes in plasma renin activity after renal artery sympathetic denervation. J Am Coll Cardiol. Published online May 3, 2021.    doi:10.1016/j.jacc.2021.04.044

Messerli FH, Bavishi C, Bangalore S. Renal denervation in hypertension: Barking up the wrong tree. J Am Coll Cardiol. Published online May 3, 2021. doi:10.1016/j.jacc.2021.04.048