arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2015-21-5-468-476arthyper-319Research ArticleОБЗОРREVIEWРенальная денервация за пределами лечения резистентной артериальной гипертензии: перспективы примененияRenal denervation beyond resistant hypertension treatment: current perspectivesСулимовВ. А.SulimovV. A.

доктор медицинских наук, профессор, заведующий кафедрой факультетской терапии № 1 лечебного факультета,

ул.Б. Пироговская, д. 6, стр. 1, Москва, 119991

MD, PhD, Associate Professor, Department of Therapy № 1, Medical Faculty,

6/1 B. Pirogovskaya street, Moscow, 119991

РодионовА. В.RodionovA. V.

кандидат медицинских наук, доцент, доцент кафедры факультетской терапии № 1 лечебного факультета,

ул.Б. Пироговская, д. 6, стр. 1, Москва, 119991

MD, PhD, Associate Professor, Department of Therapy № 1, Medical Faculty,

6/1 B. Pirogovskaya street, Moscow, 119991

rodionov@mma.ruСветанковаА. А.SvetankovaA. A.

аспирант кафедры факультетской терапии № 1 лечебного факультета,

ул.Б. Пироговская, д. 6, стр. 1, Москва, 119991

MD, PhD Student, Department of Therapy № 1, Medical Faculty,

6/1 B. Pirogovskaya street, Moscow, 119991

Государственное бюджетное образовательное учреждение высшего профессионального образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской ФедерацииРоссияI.M. Sechenov First Moscow State Medical UniversityRussian Federation201522122015215468476Copyright © Сулимов В.А., Родионов А.В., Светанкова А.А., 20152015Сулимов В.А., Родионов А.В., Светанкова А.А.Sulimov V.A., Rodionov A.V., Svetankova A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/319

Ренальная денервация — новый перспективный метод лечения резистентной артериальной гипертензии, получающий всё более широкое распространение. В последние годы эта процедура представляет интерес не только как метод дополнительного снижения артериального давления у пациентов, не отвечающих на стандартную антигипертензивную терапию, но и как способ воздействия на другие синдромы и заболевания, патогенетически связанные с гиперактивностью симпатической нервной системы. В статье представлен обзор клинических исследований ренальной денервации при инсулинорезистентности и сахарном диабете, гипертрофии левого желудочка, хронической сердечной недостаточности, синдроме обструктивного апноэ во время сна, фибрилляции предсердий и хронической болезни почек. Несмотря на противоречивые результаты исследований ренальной денервации у больных артериальной гипертензией, накапливается всё больше данных о положительном влиянии процедуры на углеводный обмен, динамику гипертрофии левого желудочка и фракции выброса. Весьма интересны, хотя и ограниченны, результаты исследований ренальной денервации у пациентов с синдромом обструктивного апноэ во время сна, а также у лиц с пароксизмальной фибрилляцией предсердий. Появляется всё больше данных о безопасности ренальной денервации при хронической болезни почек. В настоящее время продолжается изучение ренальной денервации в различных когортах пациентов.

Renal denervation is a novel promising approach for resistant hypertension management and it is getting more widespread. In recent years, this procedure has been studied not only as a method of additional reduction of blood pressure in non-responders to standard antihypertensive therapy, but also as a way of influencing other syndromes and diseases, which are related to sympathetic hyperactivity. The article provides a review of clinical trials of renal denervation in patients with insulin resistance and diabetes mellitus, left ventricular hypertrophy, heart failure, obstructive sleep apnea syndrome, atrial fibrillation and chronic kidney disease. Despite the controversial results of studies of renal denervation in patients with hypertension, there are more clinical data on the positive effect of the procedure on carbohydrate metabolism, left ventricular hypertrophy reduction and ejection fraction. The results of studies of renal denervation in patients with obstructive sleep apnea syndrome, as well as in patients with paroxysmal atrial fibrillation, are very interesting, though limited. There are more data on the safety of renal denervation in patients with chronic kidney disease. There are a lot of ongoing trials of renal denervation in different cohorts.

артериальная гипертензиярезистентная артериальная гипертензияренальная денервациясахарный диабетинсулинорезистентностьсиндром обструктивного апноэ во время снахроническая сердечная недостаточностьфибрилляция предсердийхроническая болезнь почекhypertensionresistant hypertensionrenal denervationdiabetes mellitusinsulin resistancesleep obstructive apnea syndromeatrial fibrillationchronic kidney diseaseReferencesSchlaich MP, Sobotka PA, Krum H, Whitbourn R, WaltonA, Esler MD et al. Renal denervation as a therapeutic approach for hypertension: novel implications for an old concept. Hypertension. 2009;54(6):1195–1201. doi: 10.1161/HYPERTENSIONAHA. 109.138610.Schlaich MP, Sobotka PA, Krum H, Whitbourn R, WaltonA, Esler MD et al. Renal denervation as a therapeutic approach for hypertension: novel implications for an old concept. Hypertension. 2009;54(6):1195–1201. doi: 10.1161/HYPERTENSIONAHA. 109.138610.Krum H, Schlaich M, Whitbourn R, Sobotka PA, SadowskiJ, Bartus K et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-ofprinciple cohort study. Lancet. 2009;373(9671):1275–1281. doi: 10.1016/S0140–6736 (09)60566–3.Krum H, Schlaich M, Whitbourn R, Sobotka PA, SadowskiJ, Bartus K et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-ofprinciple cohort study. Lancet. 2009;373(9671):1275–1281. doi: 10.1016/S0140–6736 (09)60566–3.Krum H, Barman N, Schlaich M. Symplicity HTN‑1 Investigators. Results presented at EuroPCR annual meeting 2013, 21–24 May 2013, Paris.Krum H, Barman N, Schlaich M. Symplicity HTN‑1 Investigators. Results presented at EuroPCR annual meeting 2013, 21–24 May 2013, Paris.Esler MD, Krum H, Sobotka PA, Schlaich M, Schmieder RE, Böhm M et al. Renal sympathetic denervation in patients with treatment resistant hypertension (The Symplicity HTN‑2 Trial): a randomised controlled trial. Lancet. 2010;376(9756):1903–1909. doi: 10.1016/S0140–6736(10)62039–9.Esler MD, Krum H, Sobotka PA, Schlaich M, Schmieder RE, Böhm M et al. Renal sympathetic denervation in patients with treatment resistant hypertension (The Symplicity HTN‑2 Trial): a randomised controlled trial. Lancet. 2010;376(9756):1903–1909. doi: 10.1016/S0140–6736(10)62039–9.Kandzari DE. Device and Clinical Trial Update: Symplicity and Spyral. Results presented at TCT annual meeting 2013. 28 October 2013, San Francisco.Kandzari DE. Device and Clinical Trial Update: Symplicity and Spyral. Results presented at TCT annual meeting 2013. 28 October 2013, San Francisco.Mancia G, Fagard R, Narkiewicz R, Redon J, Zanchetti A, Böhm M et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34 (28):2159–2219. doi: 10.1093/eurheartj/eht151.Mancia G, Fagard R, Narkiewicz R, Redon J, Zanchetti A, Böhm M et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34 (28):2159–2219. doi: 10.1093/eurheartj/eht151.Mahfoud F, Lüscher TF, Andersson B, Baumgartner I, Cifkova R, Dimario C et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J. 2013;34(28):2149–2157. doi: 10.1093/eurheartj/eht154.Mahfoud F, Lüscher TF, Andersson B, Baumgartner I, Cifkova R, Dimario C et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J. 2013;34(28):2149–2157. doi: 10.1093/eurheartj/eht154.Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M et al. Predictors of blood pressure response in the Symplcity HTN‑3 trial. Eur Heart J. 2015;36(4):219–227. doi: 10.1093/eurheartj/ehu441.Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M et al. Predictors of blood pressure response in the Symplcity HTN‑3 trial. Eur Heart J. 2015;36(4):219–227. doi: 10.1093/eurheartj/ehu441.Warchol-Celinska E, Januszewicz A, Prejbisz A, Kądziela J. Renal denervation after the simplicity HTN‑3 trial. Postepy Kardiol Interwencyjnej. 2014;10(2):75–77. doi: 10.5114/pwki.2014.43509.Warchol-Celinska E, Januszewicz A, Prejbisz A, Kądziela J. Renal denervation after the simplicity HTN‑3 trial. Postepy Kardiol Interwencyjnej. 2014;10(2):75–77. doi: 10.5114/pwki.2014.43509.Ott C, Schmieder RE. Renal denervation for resistant hypertension: past, present, and future. Curr Hypertens Rep. 2015;17 (8):577. doi: 10.1007/s11906–015–0577–6.Ott C, Schmieder RE. Renal denervation for resistant hypertension: past, present, and future. Curr Hypertens Rep. 2015;17 (8):577. doi: 10.1007/s11906–015–0577–6.Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011;123(18):1940–1946. doi: 10.1161/ CIRCULATIONAHA.110.991869.Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011;123(18):1940–1946. doi: 10.1161/ CIRCULATIONAHA.110.991869.Maraj S, Patel R, Oliveros R, Sanon S, Dao T, Hur S et al. Potential cardiometabolic benefits of renal artery denervation in diabetics.J. Diabetes Metab. 2012; S3:007. doi: 10.4172/2155–6156.S3–007.Maraj S, Patel R, Oliveros R, Sanon S, Dao T, Hur S et al. Potential cardiometabolic benefits of renal artery denervation in diabetics.J. Diabetes Metab. 2012; S3:007. doi: 10.4172/2155–6156.S3–007.Фальковская А.Ю., Мордовин В.Ф., Пекарский С.Е., Баев А. Е., Семке Г. В., Рипп Т. М. и др. Дополнительные благоприятные эффекты симпатической денервации почек при лечении резистентной артериальной гипертензии у больных сахарным диабетом 2‑го типа. Артериальная гипертензия. 2014;20(2):107–112. [Falkovskaya AYu, Mordovin VF, Pekarskiy SE, Baev AE, Semke GV, Ripp TM et al. Transcatheter renal denervation in patients with resistant hypertension and type 2 diabetes mellitus has beneficial effects beyond blood pressure reduction. Arterial’naya Gipertenziya = Arterial Hypertension. 2014;20(2):107–112. In Russian].Фальковская А.Ю., Мордовин В.Ф., Пекарский С.Е., Баев А. Е., Семке Г. В., Рипп Т. М. и др. Дополнительные благоприятные эффекты симпатической денервации почек при лечении резистентной артериальной гипертензии у больных сахарным диабетом 2‑го типа. Артериальная гипертензия. 2014;20(2):107–112. [Falkovskaya AYu, Mordovin VF, Pekarskiy SE, Baev AE, Semke GV, Ripp TM et al. Transcatheter renal denervation in patients with resistant hypertension and type 2 diabetes mellitus has beneficial effects beyond blood pressure reduction. Arterial’naya Gipertenziya = Arterial Hypertension. 2014;20(2):107–112. In Russian].Tsioufs C. Renal sympathetic denervation in metabolic syndrome (Metabolic syndrome study) [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT01911078Tsioufs C. Renal sympathetic denervation in metabolic syndrome (Metabolic syndrome study) [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT01911078Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Böhm M et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59(10):901–909. doi: 10.1016/j.jacc.2011.11.034.Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Böhm M et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59(10):901–909. doi: 10.1016/j.jacc.2011.11.034.Schirmer SH, Sayed MM, Reil JC, Ukena C, Linz D, Kindermann M et al. Improvements in left ventricular hypertrophy and diastolic function following renal denervation. J Am Coll Cardiol. 2014;63(18):1916–1923. doi: 10.1016/j.jacc.2013.10.073.Schirmer SH, Sayed MM, Reil JC, Ukena C, Linz D, Kindermann M et al. Improvements in left ventricular hypertrophy and diastolic function following renal denervation. J Am Coll Cardiol. 2014;63(18):1916–1923. doi: 10.1016/j.jacc.2013.10.073.Davies JE, Manisty CH, Petraco R, Barron AJ, Unsworth B, Mayet J et al. First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACHPilot study. Int J Cardiol. 2013;162(3):189–192. doi: 10.1016/j.ijcard.2012.09.019.Davies JE, Manisty CH, Petraco R, Barron AJ, Unsworth B, Mayet J et al. First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACHPilot study. Int J Cardiol. 2013;162(3):189–192. doi: 10.1016/j.ijcard.2012.09.019.Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;60 (2):419–424. doi: 10.1161/HYPERTENSIONAHA.112.193870.Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;60 (2):419–424. doi: 10.1161/HYPERTENSIONAHA.112.193870.Dörr O, Liebetrau C, Möllmann H, Achenbach S, Sedding D, Szardien S et al. Renal sympathetic denervation does not aggravate functional or structure renal damage acutely. J Am Coll Cardiol. 2013;61 (4):479–480. doi: 10.1016/j.jacc.2012.09.051.Dörr O, Liebetrau C, Möllmann H, Achenbach S, Sedding D, Szardien S et al. Renal sympathetic denervation does not aggravate functional or structure renal damage acutely. J Am Coll Cardiol. 2013;61 (4):479–480. doi: 10.1016/j.jacc.2012.09.051.Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23(7):1250–1257. doi: 10.1681/ASN.2011111062.Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23(7):1250–1257. doi: 10.1681/ASN.2011111062.Ott C, Mahfoud F, Schmid A, Toennes SW, Ewen S, DittingT et al. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J Hypertens. 2015;33(6):1261–1266. doi: 10.1097/HJH.0000000000000556.Ott C, Mahfoud F, Schmid A, Toennes SW, Ewen S, DittingT et al. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J Hypertens. 2015;33(6):1261–1266. doi: 10.1097/HJH.0000000000000556.Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58(5):811–817. doi: 10.1161/HYPERTENSIONAHA.111.179788.Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58(5):811–817. doi: 10.1161/HYPERTENSIONAHA.111.179788.Witkowski A, Prejbisz A, Florczak E, Kądziela J, ŚliwińskiP, Bieleń P et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011;58 (4):559–565. doi: 10.1161/HYPERTENSIONAHA.111.173799.Witkowski A, Prejbisz A, Florczak E, Kądziela J, ŚliwińskiP, Bieleń P et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011;58 (4):559–565. doi: 10.1161/HYPERTENSIONAHA.111.173799.Mahfoud F, Linz D, Mancia G, Narkiewicz K, Ruilope LM, Schlaich MP et al. Renal artery denervation for treatment of hypertensive patients with or without obstructive sleep apnea and resistant hypertension: Results from the Global SYMPLICITY Registry. J Hypertens. 2015;33: e108. doi: 10.1097/01.hjh.0000467640.39623.b2.Mahfoud F, Linz D, Mancia G, Narkiewicz K, Ruilope LM, Schlaich MP et al. Renal artery denervation for treatment of hypertensive patients with or without obstructive sleep apnea and resistant hypertension: Results from the Global SYMPLICITY Registry. J Hypertens. 2015;33: e108. doi: 10.1097/01.hjh.0000467640.39623.b2.Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A et al. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012;60 (13):1163–1170. doi: 10.1016/j.jacc.2012.05.036.Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A et al. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012;60 (13):1163–1170. doi: 10.1016/j.jacc.2012.05.036.Pokushalov E, Steinberg JS. Renal artery denervation in addition to catheter ablation to eliminate atrial fibrillation (ERADICATE-AF) [Internet]. Available from: https://clinicaltrials. gov/ct2/show/NCT01873352.Pokushalov E, Steinberg JS. Renal artery denervation in addition to catheter ablation to eliminate atrial fibrillation (ERADICATE-AF) [Internet]. Available from: https://clinicaltrials. gov/ct2/show/NCT01873352.Kaltenbach B, Franke J, Bertog SC, Steinberg DH, Hofmann I, Sievert H. Renal sympathetic denervation as secondline therapy in mild resistant hypertension: A pilot study. Catheter Cardiovasc Interv. 2013;81(2):335–339. doi: 10.1002/ccd.24557.Kaltenbach B, Franke J, Bertog SC, Steinberg DH, Hofmann I, Sievert H. Renal sympathetic denervation as secondline therapy in mild resistant hypertension: A pilot study. Catheter Cardiovasc Interv. 2013;81(2):335–339. doi: 10.1002/ccd.24557.Ott C, Mahfoud F, Schmied A, Ditting T, Sobotka PA, Veelken R et al. Renal denervation in moderate treatment resistant hypertension. J Am Coll Cardiol. 2013;62(20):1880–1886. doi: 10.1016/j.jacc.2013.06.023.Ott C, Mahfoud F, Schmied A, Ditting T, Sobotka PA, Veelken R et al. Renal denervation in moderate treatment resistant hypertension. J Am Coll Cardiol. 2013;62(20):1880–1886. doi: 10.1016/j.jacc.2013.06.023.Desch S, Okon T, Heinemann D, Kulle K, Röhnert K, Sonnabend M et al. Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension. Hypertension. 2015;65(6):1202–1208. doi: 10.1161/HYPERTENSIONAHA.115.05283.Desch S, Okon T, Heinemann D, Kulle K, Röhnert K, Sonnabend M et al. Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension. Hypertension. 2015;65(6):1202–1208. doi: 10.1161/HYPERTENSIONAHA.115.05283.Mahfoud F, Böhm M. Influence of catheter-based renal denervation in diseases with increased sympathetic activity [Internet]. Available from: https://clinicaltrials.gov/ ct2/show/NCT01888315.Mahfoud F, Böhm M. Influence of catheter-based renal denervation in diseases with increased sympathetic activity [Internet]. Available from: https://clinicaltrials.gov/ ct2/show/NCT01888315.Daemen J, Van Mieghemn N. First-in-man radial access renal denervation with the ReCor Radiance™ catheter. EuroIntervention. 2015;10(10):1209–1212. doi: 10.4244/EIJY14M12_03.Daemen J, Van Mieghemn N. First-in-man radial access renal denervation with the ReCor Radiance™ catheter. EuroIntervention. 2015;10(10):1209–1212. doi: 10.4244/EIJY14M12_03.Sievert H, Schofer J, Ormiston J, Hoppe UC, Meredith IT, Walters DL 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):1213–1220. doi: 10.4244/EIJY14M12_01.Sievert H, Schofer J, Ormiston J, Hoppe UC, Meredith IT, Walters DL 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):1213–1220. doi: 10.4244/EIJY14M12_01.Verheye S, Ormiston J, Bergmann M, Sievert H, Schwindt A, Werner N et al. Twelve-month results of the Rapid Renal Sympathetic Denervation for Resistant Hypertension Using the OneShot™ Ablation System (RAPID) study. EuroIntervention. 2015;10(10):1221–1229. doi: 10.4244/EIJY14M12_02.Verheye S, Ormiston J, Bergmann M, Sievert H, Schwindt A, Werner N et al. Twelve-month results of the Rapid Renal Sympathetic Denervation for Resistant Hypertension Using the OneShot™ Ablation System (RAPID) study. EuroIntervention. 2015;10(10):1221–1229. doi: 10.4244/EIJY14M12_02.

The authors declare that there are no conflicts of interest present.