Transurethral Renal Pelvic Denervation: A Feasibility Trial in Patients with Uncontrolled Hypertension

Abstract

Background: Endovascular renal denervation reduces blood pressure (BP). We explored an alternative approach to renal denervation using radiofrequency energy delivered across the renal pelvis utilizing the natural orifice of the urethra and the ureters. Methods: This open-label, single-arm feasibility study enrolled patients with uncontrolled hypertension despite antihypertensive drug therapy. The primary effectiveness endpoint was the change in ambulatory daytime systolic BP (SBP) 2 months following renal pelvic denervation. Results: The 18 patients (mean age 56±12 years) enrolled were taking an average of 2.7 antihypertensive drugs daily. Renal pelvic denervation reduced mean daytime SBP by 19.4 mm Hg (95% CI, −24.9 to −14.0, P <0.001) from its baseline of 148.4±8.7 mm Hg. Mean nighttime (−21.4 mm Hg [95% CI, −29.5 to −13.3]) and 24-hour (−20.3 mm Hg [95% CI, −26.2 to −14.5]) SBP each fell significantly ( P <0.001) as did the corresponding diastolic BPs ( P <0.001). Office SBP decreased from 156.5±12.3 mm Hg to 22.4 mm Hg (95% CI, −31.5 to −13.3, P <0.001) by 2 months. Office SBP decreased over time ( P =0.001 by linear trend test) starting by day 1 with a decrease of 8.3 mm Hg (95% CI, −16.9 to 0.3, P =0.057). There were no serious adverse events. Mild transitory back pain followed the procedure. Serum creatinine decreased by 0.08 mg/dL ( P =0.02) and estimated glomerular filtration rate increased by 7.2 mL/min/1.73m 2 ( P =0.03) 2 months following ablation procedure. Conclusions: Based on these initial findings, a well-powered, sham-controlled trial of renal pelvic denervation to more fully establish its safety and effectiveness is now justified in patients with uncontrolled hypertension despite drug therapy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05440513.

Durability of the Blood Pressure Effects of Renal Pelvic Denervation in Patients with Hypertension during a 12-Month Observation

“…Automated office systolic blood pressure, as reported previously [9], fell from a mean value of 156.5 ± 12.3 mm Hg by 22.8 (−30.2, −15.5) by month 2. We now report that it fell (compared with baseline) by 19.8 (−27.2, −12.4) by 6 months, and by 24.8 (33.2, 16.3) by 12 months.…”

“…As previously described [9], 41 patients signed informed consent, 10 did not meet blood pressure entry criteria, 2 were excluded by Covid, and 1 with ureteral stenosis who declined the option of an initial dilation procedure was also excluded. Of the 20 patients who underwent the procedure, only 2 were not receiving Blood Pressure Effects of Renal Pelvic Denervation Am J Nephrol 2024;55:319-328 DOI: 10.1159/000533569 antihypertension therapy, and so were not included in this analysis.…”

“…The physiologic and anatomic feasibility of this approach have been based on observations in the pig that demonstrated histopathological and hemodynamic evidence to support this approach [8]. Subsequently, we performed a feasibility study that demonstrated procedural and clinical safety as well as significant blood pressure reductions at the primary study endpoint 2 months after the denervation procedure [9]. Since the durability of device-based blood pressure interventions is so crucial, we have continued our observations to a 12-month timepoint.…”

Renal denervation: recent developments in clinical and preclinical research

“…Transurethral approaches to renal denervation are also in development and show initial promise. Although sham-controlled studies have not yet been performed, radiofrequency ablation from within the renal pelvis has the potential to reduce BP in patients with hypertension [4].…”

One More Step in the Renal Denervation Trek

“…The ultimate effect of ablating the renal nerves is interrupting both the afferent signals from the kidney to the brainstem and the efferent signals from the brainstem to the kidney. As suggested by the authors in their original publication, it may be mainly ablation of afferent signals from the kidney to the brainstem that is responsible for the early (2 months) responses in blood pressure [2], with the eventual result of a reduction in brainstem sympathetic outflow. The transurethral route undertaken in the Weber study showed an impressive daytime ambulatory systolic blood pressure response at 2 months, sustained at 12 months, of 19 mm Hg.…”