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

Dagmara Hering, David Nikoleishvili, Avtandil Imedadze, Gvantsa Dughashvili, Zurab Klimiashvili, Eter Bekaia, Tamar Shengelia, Mamuka Kobalava, Otar Goguadze, Tamar Emukhvari, Vitaly Druker, Jonathan Sackner-Bernstein, Michael A Weber, Dagmara Hering, David Nikoleishvili, Avtandil Imedadze, Gvantsa Dughashvili, Zurab Klimiashvili, Eter Bekaia, Tamar Shengelia, Mamuka Kobalava, Otar Goguadze, Tamar Emukhvari, Vitaly Druker, Jonathan Sackner-Bernstein, Michael A Weber

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 by 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/1.73m2 (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.

Keywords: ambulatory blood pressure; kidney pelvis; renal denervation; sham procedure; uncontrolled hypertension.

Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials diagram: subject disposition . ABPM indicates ambulatory BP monitoring; and BP, blood pressure.
Figure 2.
Figure 2.
Effect of renal pelvic denervation on ambulatory blood pressure (BP). A, Changes 1 and 2 months after ablation (*indicates P<0.001 by t test; overall effects for changes in systolic and diastolic blood pressure [SBP] through month 2 by linear mixed model at P<0.001) with (B) persistent 24-hour effects on SBP and diastolic blood pressure (DBP) from baseline to month 2 (means with standard errors calculated by averaging all blood pressures taken during that hour).
Figure 3.
Figure 3.
Change from baseline in office blood pressure (P values for changes in systolic and diastolic blood pressure [SBP and DBP] at each time point and overall effects by linear mixed model analysis).
Figure 4.
Figure 4.
Waterfall plots of 24-hour ambulatory blood pressure (BP) monitoring changes for each subject at month 2. SBP indicates systolic blood pressure.

References

    1. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison HC, DePalma SM, Gidding S, Jamerson KA, Jones DW, et al. . 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. J Am Coll Cardiol. 2018;71:e127–e248. doi: 10.1016/j.jacc.2017.11.006
    1. Smithwick R. Surgical treatment of hypertension. Am J Med. 1948;4:744–759. doi: 10.1016/s0002-9343(48)90397-0
    1. Conley JE, Raine F. Sympathectomy for hypertension: experience with fifty-two patients followed one to three years postoperatively. AMA Arch Surg. 1950;61:810–821. doi: 10.1001/archsurg.1950.01250020818004
    1. Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT, Leon MB, Liu M, Mauri L, Negoita M., et al. . A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393–1401. doi: 10.1056/NEJMoa1402670
    1. Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, Ewen S, Tsioufis K, Tousoulis D, Sharp ASP., et al. . Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. The Lancet. 2017;390:2160–2170. doi: 10.1016/S0140-6736(17)32281-X
    1. Kandzari DE, Böhm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, Tsioufis K, Tousoulis D, Choi JW, East C., et al. . Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. The Lancet. 2018;391:2346–2355. doi: 10.1016/S0140-6736(18)30951-6
    1. Azizi M, Sanghvi K, Saxena M, Gosse P, Reilly JP, Levy T, Rump LC, Persu A, Basile J, Bloch MJ., et al. . Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. The Lancet. 2021;397:2476–2486. doi: 10.1016/S0140-6736(21)00788-1
    1. Sakakura K, Ladich E, Cheng Q, Otsuka F, Yahagi K, Fowler DR, Kolodgie FD, Virmani R, Joner M. Anatomic assessment of sympathetic peri-arterial renal nerves in man. J Am Coll Cardiol. 2014;64:635–643. doi: 10.1016/j.jacc.2014.03.059
    1. Marfurt CF, Echtenkamp SF. Sensory innervation of the rat kidney and ureter as revealed by the anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from dorsal root ganglia: SENSORY INNERVATION OF RAT KIDNEY. J Comp Neurol. 1991;311:389–404. doi: 10.1002/cne.903110309
    1. Kopp UC. Role of renal sensory nerves in physiological and pathophysiological conditions. Am J Physiol Regul, Integr Comp Physiol. 2015;308:R79–R95. doi: 10.1152/ajpregu.00351.2014
    1. Hering D, Hubbard BS, Weber MA, Heuser RR. Impact of renal pelvic denervation on systemic hemodynamics and neurohumoral changes in a porcine model. Am J Nephrol. 2021;52:429–434. doi: 10.1159/000516186
    1. Heuser RR, Buelna TJ, Gold A, Rao RR, Van Alstine WG, Cooper RI, Desai M. NephroBlateTM Renal Denervation System: Urologic-Nephrologic Based Approach to Resistant Hypertension [Internet]. In: Heuser RR, Schlaich M, Sievert H, eds. Renal Denervation. Springer; 2015:125–134.
    1. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S., et al. . Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:7. doi: 10.1016/S0140-6736(09)60566-3
    1. SYMPLICITY-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. The Lancet. 2010;376:1903–1909. doi: 10.1016/S0140-6736(10)62039-9
    1. Beckett L, Godwin M. The BpTRU automatic blood pressure monitor compared to 24 hour ambulatory blood pressure monitoring in the assessment of blood pressure in patients with hypertension. BMC Cardiovasc Disord. 2005;5:18. doi: 10.1186/1471-2261-5-18
    1. The SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–2116. doi: 10.1056/NEJMoa1511939
    1. Weber MA, Kirtane AJ, Weir MR, Radhakrishnan J, Das T, Berk M, Mendelsohn F, Bouchard A, Larrain G, Haase M., et al. . The reduce htn: reinforce. JACC: Cardiovasc Interv. 2020;13:461–470. doi: 10.1016/j.jcin.2019.10.061
    1. Hering D, Lambert EA, Marusic P, Walton AS, Krum H, Lambert GW, Esler MD, Schlaich MP. Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension. 2013;61:457–464.
    1. Osborn JW, Foss JD. Renal nerves and long-term control of arterial pressure [Internet]. In: Terjung R, editor. Comprehensive Physiology. Wiley; 2017. [cited 2022 Aug 12]. 263–320. Available from:
    1. Atsma F, Veldhuizen I, de Kort W, van Kraaij M, Pasker-de Jong P, Deinum J. Hemoglobin level is positively associated with blood pressure in a large cohort of healthy individuals. Hypertension. 2012;60:936–941. doi: 10.1161/HYPERTENSIONAHA.112.193565
    1. Mahfoud F, Renkin J, Sievert H, Bertog S, Ewen S, Böhm M, Lengelé J-P, Wojakowski W, Schmieder R, van der Giet M., et al. . Alcohol-mediated renal denervation using the peregrine system infusion catheter for treatment of hypertension. JACC: Cardiovasc Interv. 2020;13:471–484. doi: 10.1016/j.jcin.2019.10.048

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir