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Treating Hypertension Using Renal Artery Denervation: Problems and Progress

  • Raymond R. Townsend
    Correspondence
    Address correspondence to Raymond R. Townsend, MD, Renal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania , 122 Founders Bldg, 3400 Spruce St, Philadelphia, PA 19104.
    Affiliations
    Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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      Early reports of renal denervation as a therapy for hypertension generated intense interest in this approach to management of elevated blood pressures despite ongoing treatment. The publication of the large, sham-controlled randomized clinical trial of renal denervation, Symplicity HTN-3, failed to show superiority of renal denervation by radiofrequency energy ablation compared with a sham procedure similar to the procedure used for denervation but without the application of energy to the renal artery. This prompted consideration of confounding factors and rethinking about the protocol and the procedure itself. This review describes these confounders and the progress made to improve trial design in the field of renal artery denervation.

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      References

        • Carey R.M.
        Resistant hypertension.
        Hypertension. 2013; 61: 746-750
        • Carey R.M.
        • Calhoun D.A.
        • Bakris G.L.
        • et al.
        Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association.
        Hypertension. 2018; 72: e53-e90
        • Calhoun D.A.
        • Jones D.
        • Textor S.
        • et al.
        Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research.
        Circulation. 2008; 117: e510-e526
        • Krum H.
        • Schlaich M.
        • Whitbourn R.
        • et al.
        Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study.
        Lancet. 2009; 373: 1275-1281
        • Esler M.D.
        • Krum H.
        • Sobotka P.A.
        • et al.
        Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 Trial): a randomised controlled trial.
        Lancet. 2010; 376: 1903-1909
        • Kandzari D.E.
        • Bhatt D.L.
        • Sobotka P.A.
        • et al.
        Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 trial.
        Clin Cardiol. 2012; 35: 528-535
        • Bhatt D.L.
        • Kandzari D.E.
        • O'Neill W.W.
        • et al.
        A controlled trial of renal denervation for resistant hypertension.
        N Engl J Med. 2014; 370: 1393-1401
        • Messerli F.H.
        • Bangalore S.
        Renal denervation for resistant hypertension?.
        N Engl J Med. 2014; 370: 1454-1457
        • O'Hagan K.P.
        • Thomas G.D.
        • Zambraski E.J.
        Renal denervation decreases blood pressure in DOCA-treated miniature swine with established hypertension.
        Am J Hypertens. 1990; 3: 62-64
        • Alexander B.T.
        • Hendon A.E.
        • Ferril G.
        • Dwyer T.M.
        Renal denervation abolishes hypertension in low-birth-weight offspring from pregnant rats with reduced uterine perfusion.
        Hypertension. 2005; 45: 754-758
        • Katholi R.E.
        • Naftilan A.J.
        • Oparil S.
        Importance of renal sympathetic tone in the development of DOCA-salt hypertension in the rat.
        Hypertension. 1980; 2: 266-273
        • Katholi R.E.
        • Whitlow P.L.
        • Hageman G.R.
        • Woods W.T.
        Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog.
        J Hypertens. 1984; 2: 349-359
        • Campese V.M.
        • Kogosov E.
        Renal afferent denervation prevents hypertension in rats with chronic renal failure.
        Hypertension. 1995; 25: 878-882
        • Kassab S.
        • Kato T.
        • Wilkins F.C.
        • Chen R.
        • Hall J.E.
        • Granger J.
        Renal denervation attenuates the sodium retention and hypertension associated with obesity.
        Hypertension. 1995; 25: 893-897
        • Foss J.D.
        • Wainford R.D.
        • Engeland W.C.
        • Fink G.D.
        • Osborn J.W.
        A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin.
        Am J Physiol Regul Integr Comp Physiol. 2015; 308: R112-R122
        • Kandzari D.E.
        • Bhatt D.L.
        • Brar S.
        • et al.
        Predictors of blood pressure response in the SYMPLICITY HTN-3 trial.
        Eur Heart J. 2015; 36: 219-227
        • Kandzari D.E.
        • Kario K.
        • Mahfoud F.
        • et al.
        The SPYRAL HTN Global Clinical Trial Program: rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications.
        Am Heart J. 2016; 171: 82-91
        • Mahfoud F.
        • Tunev S.
        • Ewen S.
        • et al.
        Impact of lesion placement on efficacy and safety of catheter-based radiofrequency renal denervation.
        J Am Coll Cardiol. 2015; 66: 1766-1775
        • Bakris G.L.
        • Townsend R.R.
        • Liu M.
        • et al.
        Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3.
        J Am Coll.Cardiol. 2014; 64: 1071-1078
        • Mancia G.
        • Omboni S.
        • Parati G.
        • et al.
        Lack of placebo effect on ambulatory blood pressure.
        Am J Hypertens. 1995; 8: 311-315
        • Jung O.
        • Gechter J.L.
        • Wunder C.
        • et al.
        Resistant hypertension? Assessment of adherence by toxicological urine analysis.
        J Hypertens. 2013; 31: 766-774
        • Townsend R.R.
        • Mahfoud F.
        • Kanzari D.E.
        • 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.
        Lancet. 2017; 390: 2160-2170
        • Kandzari D.E.
        • Bohm M.
        • Mahfoud F.
        • 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.
        Lancet. 2018; 391: 2346-2355
        • Azizi M.
        • Schmieder R.E.
        • Mahfoud F.
        • et al.
        Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial.
        Lancet. 2018; 391: 2335-2345
        • Mahfoud F.
        • Bakris G.L.
        • Bhatt D.
        • et al.
        Reduced blood pressure-lowering effect of catheter-based renal denervation in patients with isolated systolic hypertension: data from SYMPLICITY HTN-3 and the Global SYMPLICITY Registry.
        Eur Heart J. 2017; 38: 93-100
        • Safar M.E.
        Pulse pressure, arterial stiffness and wave reflections (augmentation index) as cardiovascular risk factors in hypertension.
        Ther Adv Cardiovasc Dis. 2008; 2: 13-24
        • Mauri L.
        • Kario K.
        • Basile J.
        • et al.
        A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: the RADIANCE-HTN and REQUIRE clinical study designs.
        Am Heart J. 2018; 195: 115-129
        • Townsend R.R.
        • Sobotka P.A.
        Catheter-based renal denervation for hypertension.
        Curr Hypertens Rep. 2018; 20: 93