杜小宇,卢成志

• 1:天津市第一中心医院心内科
• 2:天津医科大学第一中心临床学院

摘要(Abstract)：

高血压的发病率及死亡率近年来仍在不断升高，在危害人类心血管健康的同时增加了全球健康负担。经皮去肾神经术（RDN）通过抑制肾交感神经活性从而降低血压，具有广泛应用前景并为高血压治疗带来新的希望，其中经导管射频消融去肾交感神经术（RSD）已开展多项大型临床研究且陆续公布了其长期随访结果，引发了对于RDN长期疗效的全新思考。综上因素本文主要针对RSD的长期疗效及其潜在影响因素进行综述，旨在为RDN的临床应用提供参考。

关键词(KeyWords)： 经皮去肾神经术;经导管射频消融;高血压;长期疗效

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目（81970303）;; 天津市医学重点学科（专科）建设项目（TJYXZDXK-054B）

作者(Author): 杜小宇,卢成志

参考文献(References)：

• [1] NCD Risk Factor Collaboration(NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019:a pooled analysis of 1201 populationrepresentative studies with 104 million participants[J]. Lancet,2021,398(10304):957-980. DOI:10.1016/s0140-6736(21)01330-1.
• [2] Virani SS,Alonso A,Benjamin EJ,et al. Heart disease and stroke statistics-2020 update:a report from the american heart association[J]. Circulation,2020,141(9):e139-e596.DOI:10.1161/cir.0000000000000757.
• [3] Durand H,Hayes P,Morrissey EC,et al. Medication adherence among patients with apparent treatment-resistant hypertension:systematic review and meta-analysis[J]. J Hypertens,2017,35(12):2346-2357. DOI:10.1097/hjh.0000000000001502.
• [4] Frishman WH. Beta-adrenergic receptor blockers in hypertension:alive and well[J]. Prog Cardiovasc Dis,2016,59(3):247-252. DOI:10.1016/j.pcad.2016.10.005.
• [5] Kamat NV,Thabet SR,Xiao L,et al. Renal transporter activation during angiotensin-Ⅱhypertension is blunted in interferon-γ-/-and interleukin-17A-/-mice[J]. Hypertension,2015,65(3):569-576. DOI:10.1161/HYPERTENSIONAHA.114.04975.
• [6] Scholl UI,St?lting G,Nelson-Williams C,et al. Recurrent gain of function mutation in calcium channel cacna1h causes earlyonset hypertension with primary aldosteronism[J]. Elife,2015,4:e06315. DOI:10.7554/eLife.06315.
• [7] Thompson JE,Smithwick RH. Surgical measures in hypertension[J]. Geriatrics,1953,8(11):611-619.
• [8] Guyenet PG. The sympathetic control of blood pressure[J]. Nat Rev Neurosci,2006,7(5):335-346. DOI:10.1038/nrn1902.
• [9] Esler M. Sympathetic nervous system moves toward center stage in cardiovascular medicine:from thomas willis to resistant hypertension[J]. Hypertension,2014,63(3):e25-e32.DOI:10.1161/HYPERTENSIONAHA.113.02439.
• [10] Grassi G,Ram VS. Evidence for a critical role of the sympathetic nervous system in hypertension[J]. J Am Soc Hypertens,2016,10(5):457-466.DOI:10.1016/j.jash.2016.02.015.
• [11] Grassi G,Mark A,Esler M. The sympathetic nervous system alterations in human hypertension[J]. Circ Res,2015,116(6):976-990. DOI:10.1161/CIRCRESAHA.116.303604.
• [12] Shinohara K. Emerging topics on basic research in hypertension:interorgan communication and the need for interresearcher collaboration[J]. Hypertens Res,2023,46(3):638-645.DOI:10.1038/s41440-023-01176-3.
• [13] Wang HJ,Wang W,Cornish KG,et al. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure[J].Hypertension,2014,64(4):745-755. DOI:10.1161/hypertensionaha.114.03699.
• [14] Dalmasso C,Leachman JR,Ghuneim S,et al. Epididymal fat-derived sympathoexcitatory signals exacerbate neurogenic hypertension in obese male mice exposed to early life stress[J].Hypertension,2021,78(5):1434-1449. DOI:10.1161/HYPERTENSIONAHA.121.17298.
• [15] Asirvatham-Jeyaraj N,Gauthier MM,Banek CT,et al. Renal denervation and celiac ganglionectomy decrease mean arterial pressure similarly in genetically hypertensive schlager(bph/2j)mice[J]. Hypertension,2021,77(2):519-528. DOI:10.1161/HYPERTENSIONAHA.119.14069.
• [16] Sakakura K,Ladich E,Cheng Q,et al. Anatomic assessment of sympathetic peri-arterial renal nerves in man[J].J Am Coll Cardiol,2014,64(7):635-643. DOI:10.1016/j.jacc.2014.03.059.
• [17] Rao A,Krishnan N. Update on renal sympathetic denervation for the treatment of hypertension[J]. Curr Cardiol Rep,2022,24(10):1261-1271. DOI:10.1007/s11886-022-01753-x.
• [18] DiBona GF. Neural control of the kidney:Functionally specific renal sympathetic nerve fibers[J]. Am J Physiol Regul Integr Comp Physiol,2000,279(5):R1517-R1524. DOI:10.1152/ajpregu.2000.279.5.R1517.
• [19]郭炳辰，唐昊，李光辉，等.慢性心力衰竭神经调节治疗技术的应用与研究进展[J].中国介入心脏病学杂志，2023,31(8):603-608. DOI:10.3969/j.issn.1004-8812.2023.08.007.
• [20] Schlaich MP,Sobotka PA,Krum H,et al. Renal sympatheticnerve ablation for uncontrolled hypertension[J]. N Engl J Med,2009,361(9):932-934. DOI:10.1056/NEJMc0904179.
• [21] 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[J]. Lancet,2009,373(9671):1275-1281. DOI:10.1016/s0140-6736(09)60566-3.
• [22] 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[J]. Lancet,2014,383(9917):622-629. DOI:10.1016/s0140-6736(13)62192-3.
• [23] Esler MD,Krum H,Sobotka PA,et al. Renal sympathetic denervation in patients with treatment-resistant hypertension(the Symplicity HTN-2 trial):a randomised controlled trial[J].Lancet,2010,376(9756):1903-1909. DOI:10.1016/s0140-6736(10)62039-9.
• [24] Esler MD,B?hm M,Sievert H,et al. Catheterbased renal denervation for treatment of patients with treatmentresistant hypertension:36 month results from the Symplicity HTN-2 randomized clinical trial[J]. Eur Heart J,2014,35(26):1752-1759. DOI:10.1093/eurheartj/ehu209.
• [25] Mahfoud F,B?hm M,Schmieder R,et al. Effects of renal denervation on kidney function and long-term outcomes:3-year follow-up from the Global SYMPLICITY Registry[J].Eur Heart J,2019,40(42):3474-3482. DOI:10.1093/eurheartj/ehz118.
• [26] Bhatt DL,Kandzari DE,O’Neill WW,et al. A controlled trial of renal denervation for resistant hypertension[J]. N Engl J Med,2014,370(15):1393-1401. DOI:10.1056/NEJMoa1402670.
• [27] Kario K,Mahfoud F,Kandzari DE,et al. Long-term reduction in morning and nighttime blood pressure after renal denervation:36-month results from SPYRAL HTN-ON MED trial[J].Hypertens Res,2023,46(1):280-288. DOI:10.1038/s41440-022-01042-8.
• [28] B?hm M,Kario K,Kandzari DE,et al. Efficacy of catheterbased renal denervation in the absence of antihypertensive medications(SPYRAL HTN-OFF MED pivotal):a multicentre,randomised,sham-controlled trial[J]. Lancet,2020,395(10234):1444-1451. DOI:10.1016/s0140-6736(20)30554-7.
• [29] Voora R,Hinderliter AL. Modulation of sympathetic overactivity to treat resistant hypertension[J]. Curr Hypertens Rep,2018,20(11):92. DOI:10.1007/s11906-018-0893-8.
• [30] van Amsterdam WA,Blankestijn PJ,Goldschmeding R,et al. The morphological substrate for renal denervation:nerve distribution patterns and parasympathetic nerves. A post-mortem histological study[J]. Ann Anat,2016,204:71-79. DOI:10.1016/j.aanat.2015.11.004.
• [31] Liu H,Chen W,Lai Y,et al. Selective renal denervation guided by renal nerve stimulation in canine[J]. Hypertension,2019,74(3):536-545. DOI:10.1161/hypertensionaha.119.12680.
• [32] Wang J,Sun N,Ge J,et al. Rationale and design of sympathetic mapping/ablation of renal nerves trial(SMART)for the treatment of hypertension:a prospective,multicenter,singleblind,randomized and sham procedure-controlled study[J].J Cardiovasc Transl Res,2023,16(2):358-370. DOI:10.1007/s12265-022-10307-z.
• [33]张子轩，黄晶.超声消融去肾交感神经术治疗高血压的研究现状[J].心血管病学进展，2021,42(6):503-507. DOI:10.16806/j.cnki.issn.1004-3934.2021.06.007.
• [34] Rader F,Kirtane AJ,Wang Y,et al. Durability of blood pressure reduction after ultrasound renal denervation:three-year follow-up of the treatment arm of the randomised RADIANCEHTN SOLO trial[J]. EuroIntervention,2022,18(8):e677-e685. DOI:10.4244/EIJ-D-22-00305.
• [35] Azizi M,Mahfoud F,Weber MA,et al. Effects of renal denervation vs sham in resistant hypertension after medication escalation:Prespecified analysis at 6 months of the RADIANCE-HTN TRIO randomized clinical trial[J].JAMA Cardiol,2022,7(12):1244-1252. DOI:10.1001/jamacardio.2022.3904.
• [36] Samuels JA,Molony DA. In hypertension not treated with medications,renal denervation vs. sham reduced daytime ambulatory SBP at 2 mo[J]. Ann Intern Med,2023,176(6):JC68. DOI:10.7326/j23-0040.
• [37] Kandzari DE,Weber MA,Pathak A,et al. Effect of alcohol-mediated renal denervation on blood pressure in the presence of antihypertensive medications:primary results from the TARGET BPⅠrandomized clinical trial[J].Circulation,2024,149(24):1875-1884. DOI:10.1161/CIRCULATIONAHA.124.069291.
• [38] Pathak A,Rudolph UM,Saxena M,et al. Alcohol-mediated renal denervation in patients with hypertension in the absence of antihypertensive medications[J]. EuroIntervention,2023,19(7):602-611. DOI:10.4244/eij-d-23-00088.
• [39] Sesa-Ashton G,Nolde JM,Muente I,et al. Catheterbased renal denervation:9-year follow-up data on safety and blood pressure reduction in patients with resistant hypertension[J]. Hypertension,2023,80(4):811-819. DOI:10.1161/HYPERTENSIONAHA.122.20853.
• [40] Zeijen VJM,Feyz L,Nannan Panday R,et al. Long-term followup of patients undergoing renal sympathetic denervation[J]. Clin Res Cardiol,2022,111(11):1256-1268. DOI:10.1007/s00392-022-02056-5.
• [41] Panchavinnin P,Wanthong S,Roubsanthisuk W,et al. Longterm outcome of renal nerve denervation(rdn)for resistant hypertension[J]. Hypertens Res,2022,45(6):962-966.DOI:10.1038/s41440-022-00910-7.
• [42] Wang L,Li C,Li Z,et al. Ten-year follow-up of very-high risk hypertensive patients undergoing renal sympathetic denervation[J]. J Hypertens,2024,42(5):801-808. DOI:10.1097/HJH.0000000000003650.
• [43] Sesa-Ashton G,Nolde JM,Muente I,et al. Longterm blood pressure reductions following catheter-based renal denervation:a systematic review and meta-analysis[J].Hypertension,2024,81(6):e63-e70. DOI:10.1161/HYPERTENSIONAHA.123.22314.
• [44] Bhatt DL,Vaduganathan M,Kandzari DE,et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension:final follow-up of the randomised Symplicity HTN-3 trial[J]. Lancet,2022,400(10361):1405-1416.DOI:10.1016/s0140-6736(22)01787-1.
• [45] Lüscher TF,Mahfoud F. Renal nerve ablation after Symplicity HTN-3:confused at the higher level?[J]. Eur Heart J,2014,35(26):1706-1711. DOI:10.1093/eurheartj/ehu195.
• [46] Kandzari DE,B?hm 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[J]. Lancet,2018,391(10137):2346-2355. DOI:10.1016/s0140-6736(18)30951-6.
• [47] Mahfoud F,Kandzari DE,Kario K,et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs(SPYRAL HTN-ON MED):a randomised,shamcontrolled trial[J]. Lancet,2022,399(10333):1401-1410. DOI:10.1016/S0140-6736(22)00455-X.
• [48] Persu A,Stoenoiu MS,Maes F,et al. Late outcomes of renal denervation are more favourable than early ones:facts or fancies?[J]. Clin Kidney J,2023,16(12):2357-2364. DOI:10.1093/ckj/sfad231.
• [49] Mauriello A,Rovella V,Borri F,et al. Hypertension in kidney transplantation is associated with an early renal nerve sprouting[J]. Nephrol Dial Transplant,2017,32(6):1053-1060.DOI:10.1093/ndt/gfx069.
• [50] Messerli FH,Bavishi C,Brguljan J,et al. Renal denervation in the antihypertensive arsenal-knowns and known unknowns[J]. J Hypertens,2022,40(10):1859-1875. DOI:10.1097/HJH.0000000000003171.
• [51] Booth LC,Nishi EE,Yao ST,et al. Reinnervation of renal afferent and efferent nerves at 5.5 and 11 months after catheter-based radiofrequency renal denervation in sheep[J].Hypertension,2015,65(2):393-400. DOI:10.1161/HYPERTENSIONAHA.114.04176.
• [52] Sharp ASP,Tunev S,Schlaich M,et al. Histological evidence supporting the durability of successful radiofrequency renal denervation in a normotensive porcine model[J]. J Hypertens,2022,40(10):2068-2075. DOI:10.1097/HJH.0000000000003236.
• [53] Chen P,Guo Z,Chen Y,et al. The influence of inhibiting renal neural regeneration on the efficacy of renal denervation to chronic heart failure[J]. ESC Heart Fail,2021,8(6):4760-4771.DOI:10.1002/ehf2.13655.
• [54] Rodionova K,Fiedler C,Guenther F,et al. Complex reinnervation pattern after unilateral renal denervation in rats[J]. Am J Physiol Regul Integr Comp Physiol,2016,310(9):R806-R818. DOI:10.1152/ajpregu.00227.2014.
• [55]胡鑫渝，周浩，李丹，等.聚焦去肾交感神经术发展的关键--患者选择与精准消融[J].中国介入心脏病学杂志，2023,31(3):213-218. DOI:10.3969/j.issn.1004-8812.2023.03.008.
• [56] Mahfoud F,Tunev S,Ewen S,et al. Impact of lesion placement on efficacy and safety of catheter-based radiofrequency renal denervation[J]. J Am Coll Cardiol,2015,66(16):1766-1775. DOI:10.1016/j.jacc.2015.08.018.
• [57] Pekarskiy S,Baev A,Falkovskaya A,et al. Durable strong efficacy and favorable long-term renal safety of the anatomically optimized distal renal denervation according to the 3 year followup extension of the double-blind randomized controlled trial[J]. Heliyon,2022,8(1):e08747. DOI:10.1016/j.heliyon.2022.e08747.
• [58] Fengler K,Rommel KP,Blazek S,et al. A three-arm randomized trial of different renal denervation devices and techniques in patients with resistant hypertension(RADIOSOUND-HTN)[J]. Circulation,2019,139(5):590-600. DOI:10.1161/CIRCULATIONAHA.118.037654.
• [59] Persu A,Jin Y,Fadl Elmula FE,et al. Renal denervation after Symplicity HTN-3:an update[J]. Curr Hypertens Rep,2014,16(8):460. DOI:10.1007/s11906-014-0460-x.