Background: Randomized, sham-controlled trials with catheter-based radio frequency (RF) renal denervation (RDN) have demonstrated its safety and efficacy in real world populations. Sustained blood pressure reductions following RDN have been observed out to three years in multiple studies, however the physiological basis for RDN durability is unclear. We evaluated the pathophysiological outcomes in a preclinical swine model to assess the durability of RF RDN in ablating the efferent sympathetic nerves.  

Methods: Animal studies including 28 normotensive swine were conducted in accordance with published guidelines. RF RDN was performed (4 lesions per main renal artery) in the treatment group (n=14) using the Symplicity Spyral™ RDN system (Medtronic, Santa Rosa, CA, USA). A control group (n=14) had no procedure conducted. Serial histological tissue samples were harvested from both kidneys in the RDN and untreated groups at day 7 (n=6 swine per group), and 180 (n=8 per group) post-procedure. Tissue samples were bioanalytical quantified for cortical norepinephrine (NE) levels and renal cortical axon density. Tissue fibrosis, necrosis and downstream nerve fiber atrophy were also analyzed and scored. 

Results: Renal cortical axon density and NE levels were significantly reduced through 180 days following RF RDN compared to the control group (Figure). Nerve necrosis at the ablation site was observable at 7 days but was not observed at 180 days post procedure. However, nerve fibrosis and axonal loss resulting in nerve bundle atrophy distal to the ablation site were observed through 180 days. 

Conclusions: Reductions in both renal NE and cortical axon density were caused by axonal destruction and persisted 180 days after RF RDN in a normotensive swine model. These data suggest that functional nerve regrowth post-RDN is unlikely, supporting the durability of BP reduction after RF RDN.