Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation

Abstract

Background: The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP.

Objectives: The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN.

Methods: Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models.

Results: Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (-0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (-1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN.

Conclusions: Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749).

Keywords: aldosterone; hypertension; plasma renin activity; renal denervation.

Conflict of interest statement

Funding Support and Author Disclosures The SPYRAL HTN-OFF MED Pivotal trial was sponsored by Medtronic. Profs. Mahfoud and Böhm are supported by Deutsche Forschungsgemeinschaft (SFB TRR219). Prof. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie; and has received scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, and ReCor Medical. Prof. Townsend has received consultant fees from Medtronic, Axio, and Regeneron. Dr. Kandzari has received institutional research/grant support from Medtronic CardioVascular and Ablative Solutions; and has received personal consulting honoraria from Medtronic CardioVascular. Prof. Kario has received scientific support and speaker honoraria from Daichi-Sankyo, Sanwa Chemical, Boehringer Ingelheim, Omron Healthcare, A&D Inc., Fukudadenshi Inc., Medtronic, and ReCor Medical. Prof. Schmieder has received consultant fees from Medtronic and Recor; and has received grant support from Medtronic, Recor, and Ablative Solutions. Dr. Tsioufis has received honoraria for advisory boards and lectures from Medtronic, Servier, Bayer, Menarini, Novartis, AstraZeneca, Boehringer Inc., Pfizer, Pythagoras, Sanofi, and Amgen. Dr. Pocock has received consultant fees from Medtronic. Dr. Walton has served as a proctor for Medtronic and Abbott; has served on the medical advisory board for Medtronic; and has received grant support from Medtronic, Abbott, and Edwards. Prof. T. Weber has received scientific support from I.E.M. GmbH. Dr. Cohen and Mr. Fahy are employees and shareholders for Medtronic. Prof. Böhm has received consulting fees from Abbott Vascular, Bayer AG, Amgen, AstraZeneca, Servier, Medtronic, Vifor, and Boehringer Ingelheim. Prof. M. Weber has received consulting fees from Medtronic, ReCor, and Ablative Solutions. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.