cardiotomskСибирский журнал клинической и экспериментальной медициныSiberian Journal of Clinical and Experimental Medicine2713-29272713-265XTSU publishing10.29001/2073-8552-2019-34-3-21-32cardiotomsk-809Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESРенальная денервация в 2019 годуRenal denervation in 2019https://orcid.org/0000-0002-4008-4021ПекарскийС. Е.PekarskiyS. E.

д-р мед. наук, ведущий научный сотрудник отделения артериальных гипертоний, Научно-исследовательский институт кардиологии, 

634012, Томск, ул. Киевская, 111а

M.D., Dr. Sci. (Med.), Leading Research Scientist, Department of Hypertension, Cardiology Research Institute, 

111a, Kievskaya str., Tomsk, 634012

pekarski@cardio-tomsk.ruhttps://orcid.org/0000-0002-2238-4573МордовинВ. Ф.MordovinV. F.

д-р мед. наук, профессор, заведующий отделением артериальных гипертоний, Научно-исследовательский институт кардиологии,

634012, Томск, ул. Киевская, 111а

M.D., Dr. Sci. (Med.), Professor, Head of the Department of Hypertension, Cardiology Research Institute, 

111a, Kievskaya str., Tomsk, 634012

mordovin@cardio-tomsk.ruhttps://orcid.org/0000-0001-5898-0361РиппТ. М.RippT. M.

д-р мед. наук, ведущий научный сотрудник отделения артериальных гипертоний, Научно-исследовательский институт кардиологии,

634012, Томск, ул. Киевская, 111а

M.D., Dr. Sci. (Med.), Leading Research Scientist, Department of Hypertension, Cardiology Research Institute, 

111a, Kievskaya str., Tomsk, 634012

ripp@cardio-tomsk.ruhttps://orcid.org/0000-0002-5638-3034ФальковскаяА. Ю.FalkovskayaA. Yu.

канд. мед. наук, старший научный сотрудник отделения артериальных гипертоний, Научно-исследовательский институт кардиологии,

634012, Томск, ул. Киевская, 111а

M.D., Cand. Sci. (Med.), Senior Research Scientist, Department of Hypertension, Cardiology Research Institute, 

111a, Kievskaya str., Tomsk, 634012

alla@cardio-tomsk.ruТомский национальный исследовательский медицинский центр Российской академии наукРоссияTomsk National Research Medical Center, Russian Academy of SciencesRussian Federation2019011120193432132Copyright © Пекарский С.Е., Мордовин В.Ф., Рипп Т.М., Фальковская А.Ю., 20192019Пекарский С.Е., Мордовин В.Ф., Рипп Т.М., Фальковская А.Ю.Pekarskiy S.E., Mordovin V.F., Ripp T.M., Falkovskaya A.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sibjcem.ru/jour/article/view/809

В XXI веке артериальная гипертония (АГ) остается главной угрозой здоровью взрослого населения земного шара, несмотря на феноменальный прогресс в развитии антигипертензивной фармакотерапии. Сегодня в условиях доступности более 60 оригинальных препаратов для снижения артериального давления (АД), относящихся к 10 фармакологическим классам, эффективный контроль АГ достигается не более чем в половине случаев. Причиной являются фундаментальные ограничения фармакотерапии, главные из которых – развитие фармакологической/фармакокинетической толерантности («привыкания») к действию препаратов, а также невозможность полностью соблюдать режимы приема препаратов вследствие объективной истощаемости психофизиологической функции самоконтроля. Ренальная денервация (РДН) – новое немедикаментозное лечение АГ, представляющее собой мини-электрохирургическое вмешательство на симпатической системе почек, когда с помощью катетерной аблации создается постоянный блок проведения нервных импульсов по почечным нервам, что в соответствии с функцией адренорецепторов в почках увеличивает фильтрацию, уменьшает канальцевую реабсорбцию воды и снижает клубочковую секрецию ренина. После формальной неудачи данного метода в исследовании Symplicity HTN-3 с использованием одноэлектродной катетерной системы первого поколения, РДН была практически изобретена заново. В первую очередь, был радикально изменен дизайн, новые устройства стали мультиэлектродными, с трехмерным пространственным расположением электродов, гарантирующим полностью круговое воздействие и плотный контакт электродов со стенкой артерии. Другим важным усовершенствованием стала анатомическая оптимизация процедуры вмешательства с перераспределением воздействий в сегментарные ветви почечной артерии, где почечные нервы максимально концентрируются вокруг почечных сосудов. В данной статье представлен анализ текущего развития данной медицинской технологии, определены перспективы ее дальнейшего использования.

In the 21st century, hypertension remains a major health threat to the adult population worldwide, despite the phenomenal progress in the development of antihypertensive pharmacotherapy. Currently, the rate of pharmacological control of hypertension barely exceeds 50%. Indeed, pharmacotherapy is fundamentally limited by pharmacological/pharmacokinetic tolerance (adaptation) to the drugs as well as by non-compliance of patients with treatment regimens due to depletion of their psychophysiological function of self-control. Renal denervation (RDN) is a new non-drug treatment of hypertension. Renal denervation consists of a mini-electrosurgery on the renal sympathetic system where a catheter ablation is used to create a permanent block of conduction through the renal nerves. This procedure, in accordance with the function of the renal adrenergic receptors, increases glomerular filtration, reduces tubular water reabsorption, and inhibits glomerular secretion of renin. After the over-disputed failure of the early version of RDN using the first-generation single-electrode catheter system in the SYMPLICITY HTN-3 study, therapy was virtually reinvented with a new three-dimensional multi-electrode design and an anatomically optimized procedure. The new device design ensures deployment of the electrodes in a pre-defined fully circumferential pattern. Moreover, this design provides a radial contact that presses the electrodes against the arterial wall thereby maximizing the efficiency of radiofrequency (RF) tissue heating. Another major improvement of RDN therapy is the anatomical optimization of the procedure by extending the treatment into the segmental branches of the renal artery where the renal nerves concentrate the most around renal vessels. This article presents an analysis of the current state-of-the-development and future perspectives of RDN therapy.

артериальная гипертониясимпатическая нервная системаэндоваскулярные вмешательстварадиочастотная аблацияhypertensionsympathetic nervous systemendovascular therapyradiofrequency ablationReferencesGlobal health risks. Мortality and burden of disease attributable to selected major risks. Geneva: World Health Organization; 2009:62.Global health risks. Мortality and burden of disease attributable to selected major risks. Geneva: World Health Organization; 2009:62.Forouzanfar M.H., Liu P., Roth G.A., Ng M., Biryukov S. Marczak L. et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;317(2):165–182. DOI: 10.1001/jama.2016.19043.Forouzanfar M.H., Liu P., Roth G.A., Ng M., Biryukov S. Marczak L. et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;317(2):165–182. DOI: 10.1001/jama.2016.19043.Heart disease and stroke statistics-2017 update. A report from the American Heart Association. Circulation. 2017;135:e146–e603. DOI: 10.1161/CIR.0000000000000485.Heart disease and stroke statistics-2017 update. A report from the American Heart Association. Circulation. 2017;135:e146–e603. DOI: 10.1161/CIR.0000000000000485.Heilbrunn S.M., Shah P., Bristow M.R., Valantine H.A., Ginsburg R., Fowler M.B. Increased beta-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy. Circulation. 1989;79(3):483–490.Heilbrunn S.M., Shah P., Bristow M.R., Valantine H.A., Ginsburg R., Fowler M.B. Increased beta-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy. Circulation. 1989;79(3):483–490.Kramkowski K., Mogielnicki A., Buczko W. The physiological significance of the alternative pathways of angiotensin II production. J. Physiol. Pharmacol. 2006;57(4):529–539.Kramkowski K., Mogielnicki A., Buczko W. The physiological significance of the alternative pathways of angiotensin II production. J. Physiol. Pharmacol. 2006;57(4):529–539.Zisaki A., Miskovic L., Hatzimanikatis V. Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches. Current. Pharmaceutical Design. 2015;21:806–822.Zisaki A., Miskovic L., Hatzimanikatis V. Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches. Current. Pharmaceutical Design. 2015;21:806–822.Judd E., Calhoun D.A. Apparent and true resistant hypertension: definition, prevalence and outcomes. J. Hum. Hypertens. 2014;28(8):463– 468. DOI: 10.1038/jhh.2013.140.Judd E., Calhoun D.A. Apparent and true resistant hypertension: definition, prevalence and outcomes. J. Hum. Hypertens. 2014;28(8):463– 468. DOI: 10.1038/jhh.2013.140.Bramlage P., Hasford J. Blood pressure reduction, persistence and costs in the evaluation of antihypertensive drug treatment-a review. Cardiovascular. Diabetology. 2009;27(8):18. DOI: 10.1186/1475-2840-8-18.Bramlage P., Hasford J. Blood pressure reduction, persistence and costs in the evaluation of antihypertensive drug treatment-a review. Cardiovascular. Diabetology. 2009;27(8):18. DOI: 10.1186/1475-2840-8-18.Morris A.B., Li J., Kroenke K., Bruner-England T.E., Young J.M., Murrey M.D. et al. Factors associated with drug adherence and blood pressure control in patients with hypertension. Pharmacotherapy. 2006; 26(4):483–492. DOI: 10.1592/phco.26.4.483.Morris A.B., Li J., Kroenke K., Bruner-England T.E., Young J.M., Murrey M.D. et al. Factors associated with drug adherence and blood pressure control in patients with hypertension. Pharmacotherapy. 2006; 26(4):483–492. DOI: 10.1592/phco.26.4.483.Crowe D.A., Goodwin S.J., Blackman R.K., Sakellaridi S., Sponheim S.R., MacDonald A.W. et al. Prefrontal neurons transmit signals to parietal neurons that reflect executive control of cognition. Nat. Neurosci. 2013;16(10):1484–1491. DOI: 10.1038/nn.3509.Crowe D.A., Goodwin S.J., Blackman R.K., Sakellaridi S., Sponheim S.R., MacDonald A.W. et al. Prefrontal neurons transmit signals to parietal neurons that reflect executive control of cognition. Nat. Neurosci. 2013;16(10):1484–1491. DOI: 10.1038/nn.3509.Vohs K.D., Baumeister R.F., Schmeichel B.J., Twenge J.M., Nelson N.M., Tice D.M. Making choices impairs subsequent self-control: a limited-resource account of decision making, f-regulation, and active initiative. J. Pers. Soc. Psychol. 2008;94(5):883–898. DOI: 10.1037/0022-3514.94.5.883.Vohs K.D., Baumeister R.F., Schmeichel B.J., Twenge J.M., Nelson N.M., Tice D.M. Making choices impairs subsequent self-control: a limited-resource account of decision making, f-regulation, and active initiative. J. Pers. Soc. Psychol. 2008;94(5):883–898. DOI: 10.1037/0022-3514.94.5.883.Cramer J.A., Benedict A., Muszbek N., Keskinalsan A., Khan Z.M. The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review. Int. J. Clin. Pract. 2008;62(1):76–87. DOI: 10.1111/j.1742-1241.2007.01630.x.Cramer J.A., Benedict A., Muszbek N., Keskinalsan A., Khan Z.M. The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review. Int. J. Clin. Pract. 2008;62(1):76–87. DOI: 10.1111/j.1742-1241.2007.01630.x.Krum H., Schlaich M., Whitbourn R., Sobotka P.A., Sadowski J., Bartus K. et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;11;373(9671):1275–1281. DOI: 10.1016/S0140-6736(09)60566-3.Krum H., Schlaich M., Whitbourn R., Sobotka P.A., Sadowski J., Bartus K. et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;11;373(9671):1275–1281. DOI: 10.1016/S0140-6736(09)60566-3.Esler M.D., Krum H., Sobotka P.A., Schlaich M.P., Schmieder R.E., Böhm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;4;376(9756):1903–1909. DOI: 10.1016/S0140-6736(10)62039-9.Esler M.D., Krum H., Sobotka P.A., Schlaich M.P., Schmieder R.E., Böhm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;4;376(9756):1903–1909. DOI: 10.1016/S0140-6736(10)62039-9.Bhatt D.L., Kandzari D.E., O’Neill W.W., D’Agostino R., Flack J.M., Katzen B.T. et al. A controlled trial of renal denervation for resistant hypertension. N. Engl. J. Med. 2014;10;370(15):1393–1401. DOI: 10.1056/ NEJMoa1402670.Bhatt D.L., Kandzari D.E., O’Neill W.W., D’Agostino R., Flack J.M., Katzen B.T. et al. A controlled trial of renal denervation for resistant hypertension. N. Engl. J. Med. 2014;10;370(15):1393–1401. DOI: 10.1056/ NEJMoa1402670.Kandzari D.E., Bhatt D.L., Brar S., Devireddy C.M., Esler M., Fahy M. et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur. Heart J. 2015;36:219–227. DOI: 10.1093/eurheartj/ehu441.Kandzari D.E., Bhatt D.L., Brar S., Devireddy C.M., Esler M., Fahy M. et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur. Heart J. 2015;36:219–227. DOI: 10.1093/eurheartj/ehu441.Pekarskiy S., Baev A., Mordovin V., Semke G., Ripp T., Falkovskaya A. et al. Denervation of the distal renal arterial branches vs. conventional main renal artery treatment: a randomized controlled trial for treatment of resistant hypertension. Journal of Hypertension. 2017;35(2):369–375. DOI: 10.1097/HJH.0000000000001160.Pekarskiy S., Baev A., Mordovin V., Semke G., Ripp T., Falkovskaya A. et al. Denervation of the distal renal arterial branches vs. conventional main renal artery treatment: a randomized controlled trial for treatment of resistant hypertension. Journal of Hypertension. 2017;35(2):369–375. DOI: 10.1097/HJH.0000000000001160.Townsend R.R., Mahfoud F., Kandzari D.E. et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTNOFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017;390:2160–2170. DOI: 10.1016/S0140-6736(17)32281-X.Townsend R.R., Mahfoud F., Kandzari D.E. et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTNOFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017;390:2160–2170. DOI: 10.1016/S0140-6736(17)32281-X.Kandzari D.E., Bohm M., Mahfoud F., Townsend R.R., Weber M.A., Pocock S. 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 randomized trial. Lancet. 2018;391:2346–2355. DOI: 10.1016/S0140-6736(18)30951-6.Kandzari D.E., Bohm M., Mahfoud F., Townsend R.R., Weber M.A., Pocock S. 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 randomized trial. Lancet. 2018;391:2346–2355. DOI: 10.1016/S0140-6736(18)30951-6.Azizi M., Schmieder R.E., Mahfoud F., Weber MA., Daemen J., Davies J. 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. DOI: 10.1016/S0140-6736(18)31082-1.Azizi M., Schmieder R.E., Mahfoud F., Weber MA., Daemen J., Davies J. 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. DOI: 10.1016/S0140-6736(18)31082-1.Ettehad D., Emdin C.A., Kiran A., Anderson S.G., Callender T., Emberson J. et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957–967. DOI: 10.1016/S0140-6736(15)01225-8.Ettehad D., Emdin C.A., Kiran A., Anderson S.G., Callender T., Emberson J. et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957–967. DOI: 10.1016/S0140-6736(15)01225-8.

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