A Novel Catheter-Based Method for Afferent Renal Nerve Ablation in Hypertensive Sheep: Assessment of Urinary Cytokines as a Biomarker for Efficacy

Objectives: Catheter-based renal denervation (CBRDN) using radiofrequency (Medtronic) or ultrasound (ReCor) is now FDA approved for treatment-resistant hypertension (HTN). Since these CBRDN technologies destroy both afferent and efferent renal nerves, it is not known whether the mean arterial pressure (MAP) response is due to ablation of afferent or efferent renal nerves. Additionally, the non-response rate to TRDN varies between 8-37% based on the study, so a biomarker that predicts the response to CBRDN is needed. A third CBRDN technology, Ablative Solution’s Peregrine catheter, is currently in Phase III clinical trials, and destroys renal nerves by injecting the neurolytic agent ethanol into the renal artery adventitia. Our group has reported that perivascular application of capsaicin on the renal arteries, which selectively destroys afferent renal nerves, is as effective as total RDN (TRDN) in the DOCA-salt rodent models. Our long-term goal is to translate these findings to humans. The primary objective of this study was to compare the MAP response to catheter-based afferent RDN (CBARDN) using capsaicin to catheter based TRDN (CBTRDN) using ethanol in a large animal model. The secondary objective was to test the hypothesis that presence of urinary cytokines could be used to predict the MAP response to CBARDN and CBTRDN. Methods: Adult, Domestic, castrated-male sheep (n=6) weighing 60-80 kg were implanted with a subcutaneous silicone pellet containing DOCA (350mg/kg) and given access to salted (0.2% NaCl) drinking water and (180mEq Na+/kg) feed. Stellar radio telemeters were implanted for continuous measurement of MAP. 30 days following the induction of DOCA-salt HTN, the Peregrine catheter was used to perform bilateral CBTRDN (ethanol, n=2), CBARDN (capsaicin, n=2), or Sham RDN (saline, n=2). Urine samples were collected before the DOCA implantation and CBRDN treatments. One month after CBRDN, animals were terminated, and kidneys were harvested to verify denervation efficacy. Results: 30 days of DOCA-salt treatment increased the MAP from ~100mmHg to 120mmHg. In Sham RDN, MAP continued to rise over the next 30 days to ~150 mmHg. In contrast, MAP was ~120 mmHg in the CBARDN group, and ~105 mmHg in CBTRDN sheep. Furthermore, pre-CBRDN urinary IL-1α, TNFα, and IL-4 showed potential correlation (R 2 of 0.8577, 0.5410, and 0.4088, respectively) with the MAP lowering effects of afferent renal nerve ablation. Conclusion and Future Directions: These preliminary results suggest that CBTRDN and CBARDN lowers MAP in DOCA-salt HTN sheep, and this response correlates with urinary IL-1α and other cytokines. Further studies are needed to confirm these findings. Supported by NHLBI R01 HL116476 & NHLBI F30 HL167564 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.