Noninvasive Stereotactic Radiotherapy for Renal Denervation in a Swine Model

Abstract

Background: Catheter-based renal denervation (RDN) has achieved promising outcomes to treat hypertension in recent randomized controlled trials.

Objectives: The purpose of this study was to assess the feasibility, efficacy, and safety of noninvasive stereotactic body radiotherapy (SBRT) as an approach for RDN.

Methods: SBRT was performed in 24 renal arteries from 12 normotensive swine at doses of 25, 35, and 45 Gy (n = 4 each), and an additional 4 swine served as controls. Blood pressure (BP), renal function, and serum norepinephrine (NE) values were obtained at baseline and at 7 days, 1 month, and 3 months after SBRT. Abdominal contrast-enhanced computed tomography (CT) was performed after 3 months before euthanasia. Renal NE concentration was determined, and histological analysis and immunohistochemistry against tyrosine hydroxylase were performed.

Results: SBRT procedure was successful in all 12 swine. BP was comparable among groups. Serum and renal NE levels at 3 months were significantly lower in treatment groups compared with control group. Furthermore, SBRT resulted in significantly greater nerve injury score and lower tyrosine hydroxylase score compared with control subjects, whereas there were no statistical differences between SBRT groups. Circumferential lesions created with 35 and 45 Gy were significantly greater than with 25 Gy. CT and histology analysis revealed that animals receiving 35 and 45 Gy experienced more collateral damage, which was minimal in the 25-Gy group.

Conclusions: Noninvasive SBRT was feasible and effective for complete, circumferential RDN in a swine model, with dosage at 25 Gy providing the safest short-term profile.

Keywords: hypertension; noninvasive; norepinephrine; renal artery; renal denervation; stereotactic radioablation.