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Current Hypertension Reviews

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ISSN (Print): 1573-4021
ISSN (Online): 1875-6506

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Review Article

Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment

Author(s): Anthony L. Wilson, Jason Gandhi, Yiji Suh, Gunjan Joshi, Noel L. Smith and Sardar Ali Khan*

Volume 16, Issue 2, 2020

Page: [115 - 127] Pages: 13

DOI: 10.2174/1573402115666190301154100

Abstract

Background: Advances in treatment and increased awareness have improved the prognosis for many patients with hypertension (HTN). Resistant hypertension (RH) refers to a subset of hypertensive individuals who fail to achieve a desired blood pressure (BP) despite concurrent use of 3 different classes antihypertensive agents, one being a diuretic, and proper lifestyle changes. The prevalence and prognosis of RH are unclear owing to its heterogeneous etiologies, risk factors, and secondary comorbidities. Previous research has provided evidence that increased renal sympathetic nerve activity (RSNA) within the renal artery contributes to RH development. Renal denervation (RDN) is a procedure that attempts to ameliorate the effects of heightened RSNA via ablation renal sympathetic fibers. BP reductions associated with RDN may be attributed to decreased norepinephrine spillover, restoration of natriuresis, increasing renal blood flow, and lowering plasma renin activity. Early clinical trials perpetuated positive results, and enthusiasm grew exponentially. However, recent clinical trials have called into question RDN's efficacy. Numerous limitations must be addressed to discern the true effectiveness of RDN as a therapeutic option for RH.

Objective: We aimed to review the current understanding of RH, the anatomy of renal arteries, physiology of RH on renal arteries, anatomical pathways of the sympathetic involved in RH, RDN as a treatment option, and all relevant clinical trials treating RH with RDN.

Methods: We piloted a MEDLINE® database search of literature extending from 1980 to 2017, with emphasis on the previous five years, combining keywords such as "resistant hypertension" and "renal denervation."

Conclusion: A plethora of information is available regarding heightened RSNA leading to RH. RDN as a possible treatment option has shown a range of results. Reconciling RDN's true efficacy requires future trials to increased sites of nerve ablation, standardized protocol, increased anatomical understanding per individual basis, stricter guidelines regarding study design, increased operator experience, and integrating the use of a multielectrode catheter.

Keywords: Resistant hypertension, renal denervation, renal artery, renal sympathetic nerve activity, nerve ablation, stroke.

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[1]
Hyman DJ, Pavlik VN. Characteristics of patients with uncontrolled hypertension in the United States. N Engl J Med 2001; 345(7): 479-86.
[http://dx.doi.org/10.1056/NEJMoa010273] [PMID: 11519501]
[2]
Katholi RE, Rocha-Singh KJ. The role of renal sympathetic nerves in hypertension: Has percutaneous renal denervation refocused attention on their clinical significance? Prog Cardiovasc Dis 2009; 52(3): 243-8.
[http://dx.doi.org/10.1016/j.pcad.2009.09.003] [PMID: 19917336]
[3]
Gulati R, Raphael CE, Negoita M, Pocock SJ, Gersh BJ. The rise, fall, and possible resurrection of renal denervation. Nat Rev Cardiol 2016; 13(4): 238-44.
[http://dx.doi.org/10.1038/nrcardio.2016.1] [PMID: 26843285]
[4]
Rimoldi SF, Scherrer U, Messerli FH. Secondary arterial hypertension: when, who, and how to screen? Eur Heart J 2014; 35(19): 1245-54.
[http://dx.doi.org/10.1093/eurheartj/eht534] [PMID: 24366917]
[5]
Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology. Circulation 2000; 101(3): 329-35.
[http://dx.doi.org/10.1161/01.CIR.101.3.329] [PMID: 10645931]
[6]
Eckel RH, Jakicic JM, Ard JD, et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129(25)(Suppl. 2): S76-99.
[http://dx.doi.org/10.1161/01.cir.0000437740.48606.d1] [PMID: 24222015]
[7]
Officers A. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288(23): 2981-97.
[http://dx.doi.org/10.1001/jama.288.23.2981] [PMID: 12479763]
[8]
Ghofrani H, Weaver FA, Nadim MK. Resistant hypertension: medical management and alternative therapies. Cardiol Clin 2015; 33(1): 75-87.
[http://dx.doi.org/10.1016/j.ccl.2014.09.003] [PMID: 25439332]
[9]
Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension 2011; 57(6): 1076-80.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.170308] [PMID: 21502568]
[10]
Pimenta E, Calhoun DA. Resistant hypertension: Incidence, prevalence, and prognosis. Circulation 2012; 125(13): 1594-6.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.097345] [PMID: 22379111]
[11]
Krum H, Schlaich M, Sobotka P. Renal sympathetic nerve ablation for treatment resistant hypertension. Br J Clin Pharmacol 2013; 76(4): 495-503.
[http://dx.doi.org/10.1111/bcp.12171] [PMID: 23819768]
[12]
Yaxley JP, Thambar SV. Resistant hypertension: An approach to management in primary care. J Family Med Prim Care 2015; 4(2): 193-9.
[http://dx.doi.org/10.4103/2249-4863.154630] [PMID: 25949966]
[13]
Steckelings UM, Kloet A, Sumners C. Centrally mediated cardiovascular actions of the angiotensin II type 2 receptor. Trends Endocrinol Metab 2017; 28(9): 684-93.
[http://dx.doi.org/10.1016/j.tem.2017.06.002] [PMID: 28733135]
[14]
DiBona GF. Neural control of the kidney: Functionally specific renal sympathetic nerve fibers. Am J Physiol Regul Integr Comp Physiol 2000; 279(5): R1517-24.
[http://dx.doi.org/10.1152/ajpregu.2000.279.5.R1517] [PMID: 11049831]
[15]
Shaw JA, Warren JL. Resistant hypertension and renal denervation where to now? Cardiovasc Ther 2015; 33(1): 9-14.
[http://dx.doi.org/10.1111/1755-5922.12103] [PMID: 25565369]
[16]
Gonzaga CC, Calhoun DA. 2008 American Heart Association Statement on diagnosis, evaluation, and treatment of resistant hypertension: what should we remember in everyday practice? Pol Arch Med Wewn 2008; 118(7-8): 396-7.
[http://dx.doi.org/10.20452/pamw.428] [PMID: 18714732]
[17]
Sarafidis PA. Epidemiology of resistant hypertension. J Clin Hypertens (Greenwich) 2011; 13(7): 523-8.
[http://dx.doi.org/10.1111/j.1751-7176.2011.00445.x] [PMID: 21762366]
[18]
Sarganas G, Neuhauser HK. Untreated, uncontrolled, and apparent resistant hypertension: Results of the German health examination survey 2008-2011. J Clin Hypertens (Greenwich) 2016; 18(11): 1146-54.
[http://dx.doi.org/10.1111/jch.12886] [PMID: 27481706]
[19]
Grigoryan L, Pavlik VN, Hyman DJ. Characteristics, drug combinations and dosages of primary care patients with uncontrolled ambulatory blood pressure and high medication adherence. J Am Soc Hypertens 2013; 7(6): 471-6.
[http://dx.doi.org/10.1016/j.jash.2013.06.004] [PMID: 23890931]
[20]
Townsend RR. Pathogenesis of drug-resistant hypertension. Semin Nephrol 2014; 34(5): 506-13.
[http://dx.doi.org/10.1016/j.semnephrol.2014.08.004] [PMID: 25416659]
[21]
Calhoun DA, 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. Hypertension 2008; 51(6): 1403-19.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.189141] [PMID: 18391085]
[22]
Eskås PA, Heimark S, Eek Mariampillai J, Larstorp AC, Fadl Elmula FE, Høieggen A. Adherence to medication and drug monitoring in apparent treatment-resistant hypertension. Blood Press 2016; 25(4): 199-205.
[http://dx.doi.org/10.3109/08037051.2015.1121706] [PMID: 26729283]
[23]
Mariampillai JE, Eskås PA, Heimark S, et al. Apparent treatment-resistant hypertension - patient-physician relationship and ethical issues. Blood Press 2017; 26(3): 133-8.
[http://dx.doi.org/10.1080/08037051.2016.1277129] [PMID: 28078909]
[24]
Egan BM, Zhao Y, Li J, et al. Prevalence of optimal treatment regimens in patients with apparent treatment-resistant hypertension based on office blood pressure in a community-based practice network. Hypertension 2013; 62(4): 691-7.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01448] [PMID: 23918752]
[25]
Egan BM. Treatment resistant hypertension. Ethn Dis 2015; 25(4): 495-8.
[http://dx.doi.org/10.18865/ed.25.4.495] [PMID: 26674466]
[26]
Pinto-Sietsma SJ, Hillege HL, Janssen WM. Inadequate management of blood pressure in a hypertensive population. N Engl J Med 1999; 340(20): 1593-5.
[http://dx.doi.org/10.1056/NEJM199905203402015] [PMID: 10336363]
[27]
Coppolino G, Pisano A, Rivoli L, Bolignano D. Renal denervation for resistant hypertension. Cochrane Database Syst Rev 2017; 2(2) CD011499
[http://dx.doi.org/10.1002/14651858.CD011499.pub2] [PMID: 28220472]
[28]
Sarwar MS, Islam MS, Al Baker SM, Hasnat A. Resistant hypertension: underlying causes and treatment. Drug Res (Stuttg) 2013; 63(5): 217-23.
[http://dx.doi.org/10.1055/s-0033-1337930] [PMID: 23526242]
[29]
Khawaja Z, Wilcox CS. Role of the kidneys in resistant hypertension. Int J Hypertens 2011; 2011 143471
[http://dx.doi.org/10.4061/2011/143471] [PMID: 21461391]
[30]
Doroszko A, Janus A, Szahidewicz-Krupska E, Mazur G, Derkacz A. Resistant Hypertension. Adv Clin Exp Med 2016; 25(1): 173-83.
[http://dx.doi.org/10.17219/acem/58998] [PMID: 26935512]
[31]
El Rouby N, Cooper-DeHoff RM. Genetics of resistant hypertension: A novel pharmacogenomics phenotype. Curr Hypertens Rep 2015; 17(9): 583.
[http://dx.doi.org/10.1007/s11906-015-0583-8] [PMID: 26198781]
[32]
Donner KM, Hiltunen TP, Suonsyrjä T, et al. CYP2C9 genotype modifies activity of the renin-angiotensin-aldosterone system in hypertensive men. J Hypertens 2009; 27(10): 2001-9.
[http://dx.doi.org/10.1097/HJH.0b013e32832f4fae] [PMID: 19593208]
[33]
Faselis C, Doumas M, Papademetriou V. Common secondary causes of resistant hypertension and rational for treatment. Int J Hypertens 2011. 2011236239
[http://dx.doi.org/10.4061/2011/236239] [PMID: 21423678]
[34]
Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40(6): 892-6.
[http://dx.doi.org/10.1161/01.HYP.0000040261.30455.B6] [PMID: 12468575]
[35]
Logan AG, Perlikowski SM, Mente A, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens 2001; 19(12): 2271-7.
[http://dx.doi.org/10.1097/00004872-200112000-00022] [PMID: 11725173]
[36]
Papanastasiou L, Markou A, Pappa T, et al. Primary aldosteronism in hypertensive patients: Clinical implications and target therapy. Eur J Clin Invest 2014; 44(8): 697-706.
[http://dx.doi.org/10.1111/eci.12286] [PMID: 24909545]
[37]
Acelajado MC, Calhoun DA. Aldosteronism and resistant hypertension. Int J Hypertens 2011; 2011 837817
[http://dx.doi.org/10.4061/2011/837817]
[38]
Bravo EL, Fouad-Tarazi FM, Tarazi RC, Pohl M, Gifford RW, Vidt DG. Clinical implications of primary aldosteronism with resistant hypertension. Hypertension 1988; 11(2 Pt 2): I207-11.
[http://dx.doi.org/10.1161/01.HYP.11.2_Pt_2.I207] [PMID: 3346059]
[39]
De Biase A, Varrenti M, Meani P, et al. Renal artery stenosis as the cause of resistant arterial hypertension: An unusual technique for revascularization. J Clin Hypertens (Greenwich) 2014; 16(7): 536-7.
[http://dx.doi.org/10.1111/jch.12331] [PMID: 24754495]
[40]
Khamanarong K, Prachaney P, Utraravichien A, Tong-Un T, Sripaoraya K. Anatomy of renal arterial supply. Clin Anat 2004; 17(4): 334-6.
[http://dx.doi.org/10.1002/ca.10236] [PMID: 15108340]
[41]
Hering D, Marusic P, Walton AS, et al. Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension. Int J Cardiol 2016; 202: 388-93.
[http://dx.doi.org/10.1016/j.ijcard.2015.09.015] [PMID: 26432488]
[42]
Glodny B, Cromme S, Reimer P, Lennarz M, Winde G, Vetter H. Hypertension associated with multiple renal arteries may be renin dependent. J Hypertens 2000; 18(10): 1437-44.
[http://dx.doi.org/10.1097/00004872-200018100-00011] [PMID: 11057431]
[43]
Verloop WL, Vink EE, Spiering W, et al. Renal denervation in multiple renal arteries. Eur J Clin Invest 2014; 44(8): 728-35.
[http://dx.doi.org/10.1111/eci.12289] [PMID: 24931208]
[44]
DiBona GF, Esler M. Translational medicine: The antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol 2010; 298(2): R245-53.
[http://dx.doi.org/10.1152/ajpregu.00647.2009] [PMID: 19955493]
[45]
Id D, Kaltenbach B, Bertog SC, et al. Does the presence of accessory renal arteries affect the efficacy of renal denervation? JACC Cardiovasc Interv 2013; 6(10): 1085-91.
[http://dx.doi.org/10.1016/j.jcin.2013.06.007] [PMID: 24156968]
[46]
Mahfoud F, Bhatt DL. Catheter-based renal denervation: The black box procedure. JACC Cardiovasc Interv 2013; 6(10): 1092-4.
[http://dx.doi.org/10.1016/j.jcin.2013.09.001] [PMID: 24156969]
[47]
Esler M. Renal denervation: Not as easy as it looks. Sci Transl Med 2015; 7(285) 285fs18
[http://dx.doi.org/10.1126/scitranslmed.aaa5457] [PMID: 25925679]
[48]
Iliescu R, Lohmeier TE, Tudorancea I, Laffin L, Bakris GL. Renal denervation for the treatment of resistant hypertension: Review and clinical perspective. Am J Physiol Renal Physiol 2015; 309(7): F583-94.
[http://dx.doi.org/10.1152/ajprenal.00246.2015] [PMID: 26224718]
[49]
Kaplan NM. Resistant hypertension. J Hypertens 2005; 23(8): 1441-4.
[http://dx.doi.org/10.1097/01.hjh.0000174968.72212.ac] [PMID: 16003165]
[50]
Kannan A, Medina RI, Nagajothi N, Balamuthusamy S. Renal sympathetic nervous system and the effects of denervation on renal arteries. World J Cardiol 2014; 6(8): 814-23.
[http://dx.doi.org/10.4330/wjc.v6.i8.814] [PMID: 25228960]
[51]
Johns EJ. The neural regulation of the kidney in hypertension and renal failure. Exp Physiol 2014; 99(2): 289-94.
[http://dx.doi.org/10.1113/expphysiol.2013.072686] [PMID: 23955311]
[52]
DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev 1997; 77(1): 75-197.
[http://dx.doi.org/10.1152/physrev.1997.77.1.75] [PMID: 9016301]
[53]
van de Borne P. The kidney and the sympathetic system: a short review. Curr Clin Pharmacol 2013; 8(3): 175-81.
[http://dx.doi.org/10.2174/15748847113089990049] [PMID: 23150921]
[54]
Riccio E, Esposito G, Franzone A, Imbriaco M, Santangelo M, Pisani A. Renal sympathetic-nerve ablation for uncontrolled hypertension in a patient with single-kidney autosomal dominant polycystic kidney disease. J Clin Hypertens (Greenwich) 2014; 16(5): 385-6.
[http://dx.doi.org/10.1111/jch.12277] [PMID: 24621146]
[55]
Papademetriou V, Doumas M, Tsioufis K. Renal sympathetic denervation for the treatment of difficult-to-control or resistant hypertension. Int J Hypertens 2011; 2011 196518
[http://dx.doi.org/10.4061/2011/196518] [PMID: 21629864]
[56]
Katholi RE. Renal nerves in the pathogenesis of hypertension in experimental animals and humans. Am J Physiol 1983; 245(1): F1-F14.
[http://dx.doi.org/10.1152/ajprenal.1983.245.1.F1] [PMID: 6346899]
[57]
Katholi RE. Renal nerves and hypertension: An update. Fed Proc 1985; 44(13): 2846-50.
[PMID: 3899731]
[58]
Thomas P, Dasgupta I. The role of the kidney and the sympathetic nervous system in hypertension. Pediatr Nephrol 2015; 30(4): 549-60.
[http://dx.doi.org/10.1007/s00467-014-2789-4] [PMID: 24609827]
[59]
Ciriello J, de Oliveira CV. Renal afferents and hypertension. Curr Hypertens Rep 2002; 4(2): 136-42.
[http://dx.doi.org/10.1007/s11906-002-0038-x] [PMID: 11884269]
[60]
Phillips JK. Pathogenesis of hypertension in renal failure: role of the sympathetic nervous system and renal afferents. Clin Exp Pharmacol Physiol 2005; 32(5-6): 415-8.
[http://dx.doi.org/10.1111/j.1440-1681.2005.04204.x] [PMID: 15854151]
[61]
Henegar JR, Zhang Y, Hata C, Narciso I, Hall ME, Hall JE. Catheter-based radiofrequency renal denervation: Location effects on renal norepinephrine. Am J Hypertens 2015; 28(7): 909-14.
[http://dx.doi.org/10.1093/ajh/hpu258] [PMID: 25576624]
[62]
Henegar JR, Zhang Y, De Rama R, Hata C, Hall ME, Hall JE. Catheter-based radiorefrequency renal denervation lowers blood pressure in obese hypertensive dogs. Am J Hypertens 2014; 27(10): 1285-92.
[http://dx.doi.org/10.1093/ajh/hpu048] [PMID: 24709437]
[63]
Jacob F, LaBine BG, Ariza P, Katz SA, Osborn JW. Renal denervation causes chronic hypotension in rats: Role of beta1-adrenoceptor activity. Clin Exp Pharmacol Physiol 2005; 32(4): 255-62.
[http://dx.doi.org/10.1111/j.1440-1681.2005.04179.x] [PMID: 15810988]
[64]
Esler M, Guo L. The future of renal denervation. Auton Neurosci 2017; 204: 131-8.
[http://dx.doi.org/10.1016/j.autneu.2016.08.004] [PMID: 27546827]
[65]
Hasking GJ, Esler MD, Jennings GL, Dewar E, Lambert G. Norepinephrine spillover to plasma during steady-state supine bicycle exercise. Comparison of patients with congestive heart failure and normal subjects. Circulation 1988; 78(3): 516-21.
[http://dx.doi.org/10.1161/01.CIR.78.3.516] [PMID: 3409496]
[66]
Esler M. Renal denervation for treatment of drug-resistant hypertension. Trends Cardiovasc Med 2015; 25(2): 107-15.
[http://dx.doi.org/10.1016/j.tcm.2014.09.014] [PMID: 25467242]
[67]
Esler M, Jennings G, Lambert G, Meredith I, Horne M, Eisenhofer G. Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. Physiol Rev 1990; 70(4): 963-85.
[http://dx.doi.org/10.1152/physrev.1990.70.4.963] [PMID: 1977182]
[68]
Egan BM. Renal sympathetic denervation: A novel intervention for resistant hypertension, insulin resistance, and sleep apnea. Hypertension 2011; 58(4): 542-3.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.179101] [PMID: 21844486]
[69]
Townsend RR, Mahfoud F, Kandzari DE, et al. SPYRAL HTN-OFF MED trial investigators*. 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(10108): 2160-70.
[http://dx.doi.org/10.1016/S0140-6736(17)32281-X] [PMID: 28859944]
[70]
Mabin T, Sapoval M, Cabane V, Stemmett J, Iyer M. First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. EuroIntervention 2012; 8(1): 57-61.
[http://dx.doi.org/10.4244/EIJV8I1A10] [PMID: 22580249]
[71]
Ormiston JA, Watson T, van Pelt N, et al. First-in-human use of the OneShot™ renal denervation system from Covidien. EuroIntervention 2013; 8(9): 1090-4.
[http://dx.doi.org/10.4244/EIJV8I9A166] [PMID: 23339814]
[72]
Sievert H, Schofer J, Ormiston J, et al. Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study. EuroIntervention 2015; 10(10): 1213-20.
[http://dx.doi.org/10.4244/EIJY14M12_01] [PMID: 25452197]
[73]
Worthley SG, Tsioufis CP, Worthley MI, et al. Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: The EnligHTN I trial. Eur Heart J 2013; 34(28): 2132-40.
[http://dx.doi.org/10.1093/eurheartj/eht197] [PMID: 23782649]
[74]
Worthley SG, Wilkins GT, Webster MW, et al. Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension. Atherosclerosis 2017; 262: 94-100.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.04.022] [PMID: 28531827]
[75]
Kandzari DE, Bhatt DL, Sobotka PA, et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 Trial. Clin Cardiol 2012; 35(9): 528-35.
[http://dx.doi.org/10.1002/clc.22008] [PMID: 22573363]
[76]
Desch S, Okon T, Heinemann D, et al. Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension. Hypertension 2015; 65(6): 1202-8.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05283] [PMID: 25824248]
[77]
Bhatt DL, Kandzari DE, O’Neill WW, et al. SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med 2014; 370(15): 1393-401.
[http://dx.doi.org/10.1056/NEJMoa1402670] [PMID: 24678939]
[78]
Azizi M, Sapoval M, Gosse P, et al. Renal Denervation for Hypertension (DENERHTN) investigators. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): A multicentre, open-label, randomised controlled trial. Lancet 2015; 385(9981): 1957-65.
[http://dx.doi.org/10.1016/S0140-6736(14)61942-5] [PMID: 25631070]
[79]
Rosa J, Widimský P, Toušek P, et al. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study. Hypertension 2015; 65(2): 407-13.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04019] [PMID: 25421981]
[80]
Kario K, Ogawa H, Okumura K, et al. SYMPLICITY HTN-Japan Investigators. SYMPLICITY HTN-Japan - First randomized controlled trial of catheter-based renal denervation in Asian patients. Circ J 2015; 79(6): 1222-9.
[http://dx.doi.org/10.1253/circj.CJ-15-0150] [PMID: 25912693]
[81]
Böhm M, Mahfoud F, Ukena C, et al. GSR Investigators. First report of the Global SYMPLICITY Registry on the effect of renal artery denervation in patients with uncontrolled hypertension. Hypertension 2015; 65(4): 766-74.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.05010] [PMID: 25691618]
[82]
Verheye S, Ormiston J, Bergmann MW, et al. Twelve-month results of the rapid renal sympathetic denervation for resistant hypertension using the OneShotTM ablation system (RAPID) study. EuroIntervention 2015; 10(10): 1221-9.
[http://dx.doi.org/10.4244/EIJY14M12_02] [PMID: 25452198]
[83]
Fadl Elmula FE, Hoffmann P, Larstorp AC, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension 2014; 63(5): 991-9.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03246] [PMID: 24591332]
[84]
Fadl Elmula FE, Jin Y, Yang WY, et al. European Network Coordinating Research On Renal Denervation (ENCOReD) Consortium. Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension. Blood Press 2015; 24(5): 263-74.
[http://dx.doi.org/10.3109/08037051.2015.1058595] [PMID: 26194721]
[85]
Mahfoud F, Ukena C, Schmieder RE, et al. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation 2013; 128(2): 132-40.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000949] [PMID: 23780578]
[86]
Vogel B, Kirchberger M, Zeier M, et al. Renal sympathetic denervation therapy in the real world: Results from the Heidelberg registry. Clin Res Cardiol 2014; 103(2): 117-24.
[http://dx.doi.org/10.1007/s00392-013-0627-5] [PMID: 24126436]
[87]
Hering D, Mahfoud F, Walton AS, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol 2012; 23(7): 1250-7.
[http://dx.doi.org/10.1681/ASN.2011111062] [PMID: 22595301]
[88]
Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M. Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): A randomised controlled trial. Lancet 2010; 376(9756): 1903-9.
[http://dx.doi.org/10.1016/S0140-6736(10)62039-9] [PMID: 21093036]
[89]
Krum H, Schlaich MP, Sobotka PA, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: Final 3-year report of the Symplicity HTN-1 study. Lancet 2014; 383(9917): 622-9.
[http://dx.doi.org/10.1016/S0140-6736(13)62192-3] [PMID: 24210779]
[90]
Esler M. Renal denervation for hypertension: Observations and predictions of a founder. Eur Heart J 2014; 35(18): 1178-85.
[http://dx.doi.org/10.1093/eurheartj/ehu091] [PMID: 24598982]
[91]
Hameed MA, Pucci M, Martin U, et al. Renal denervation in patients with uncontrolled hypertension and confirmed adherence to antihypertensive medications. J Clin Hypertens (Greenwich) 2016; 18(6): 565-71.
[http://dx.doi.org/10.1111/jch.12713] [PMID: 26434739]
[92]
Kandzari DE, Bhatt DL, Brar S, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J 2015; 36(4): 219-27.
[http://dx.doi.org/10.1093/eurheartj/ehu441] [PMID: 25400162]
[93]
Dimitriadis K, Tsioufis C, Tousoulis D. Finding the best ablation strategy for renal denervation: A continuing saga. J Clin Hypertens (Greenwich) 2017; 19(4): 379-80.
[http://dx.doi.org/10.1111/jch.12981] [PMID: 28322494]
[94]
Mahfoud F, Lüscher TF. Renal denervation: Symply trapped by complexity? Eur Heart J 2015; 36(4): 199-202.
[http://dx.doi.org/10.1093/eurheartj/ehu450] [PMID: 25400163]
[95]
Lambert T, Nahler A, Rohla M, et al. Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation. Int J Cardiol 2016; 220: 273-8.
[http://dx.doi.org/10.1016/j.ijcard.2016.06.110] [PMID: 27390940]
[96]
Bakris GL, Townsend RR, Liu M, et al. SYMPLICITY HTN-3 Investigators. Impact of renal denervation on 24-hour ambulatory blood pressure: Results from SYMPLICITY HTN-3. J Am Coll Cardiol 2014; 64(11): 1071-8.
[http://dx.doi.org/10.1016/j.jacc.2014.05.012] [PMID: 24858423]
[97]
Xu J, Hering D, Sata Y, et al. Renal denervation: current implications and future perspectives. Clin Sci (Lond) 2014; 126(1): 41-53.
[http://dx.doi.org/10.1042/CS20120581] [PMID: 24020446]

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