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1、Management of Renovascular Hypertension,阜外心血管病医院心内科蒋雄京,Interrelation among Renal Artery Stenosis,Hypertension,and Chronic Renal Failure,Definition of Renal Artery StenosisRenal artery stenosis(RAS)is defined as narrowing of the lumen of the renal artery.*angiographic diameter stenosis50%*translesion
2、al pressure gradient of 20 mm Hg peak systolic or 10 mm Hg mean The most common causes of RAS are atherosclerosis(80%),aortoarteritis(15%),and fibromuscular dysplasia(5%)in China,Angiographic Appearance of the Three Common Forms of Renal Artery Stenosis,Prevalence,1.13%in hypertensive population2.20
3、30%in patients with secondary hypertension,Incidence of Renal Artery Stenosis at Cardiac Catheterization,Authors Year Country Patients Age CAD(%)HT(%)RAS(%)Crowley 1998 USA 14152 61 89 72 6.3Conlon 2000 Ireland 3987 52 100 58 6.3Weber 2002 Austria 177 63 62 67 11Yamashita 2002 Japan 289 66 76 48 7Ri
4、hal 2002 USA 297 65 NA 100 19.2Buller 2004 Canada 837 67 68 32 14.3Addad 2005 Tunisia 300 58 100 35 9CAD=Coronary artery disease;HTN=Hypertension;RAS=significant renal artery stenosis;NA=nonavailable.,Incidence of Renal Artery Stenosis at Cardiac Catheterizationin Chinese population,Progressive Athe
5、rosclerosis,Renal Artery Stenosis,and Ischemic Nephropathy,the clinical manifestations of ARVD,Clinical features suggestive of renovascular hypertensionJNC-VI,Onset of hypertension aged30 y;Abdominal bruit;Accelerated or resistant hypertension;Flash pulmonary edema with normal left ventricular funct
6、ion;Renal failure of uncertain cause;Coexisting,diffuse atherosclerotic vascular diseaseAcute renal failure precipitate by antihypertensive therapy,particularly ACEI or AII receptor blockers;In the presence of these clinical clues the prevalence of RVH is 40%.,Screening for Renovascular Hypertension
7、,1.Radionuclide renal fractional flow/GFR2.Plasma renin activity3.Captopril renoscitigraphy4.Color dopplor ultrasonography5.MR Angiography/CT Angiography,Multi-slices CTA is most useful for RAS screening,Severity of renal vascular disease predicts mortality in patients undergoing coronary angiograph
8、yKidney International(2001)60,14901497,Clinical Criteria for Revascularization,Hypertension:accelerated hypertension;refractory hypertension;malignant hypertension;hypertension with a unilateral small kidney;or hypertension with intolerance to medication.Renal salvage:sudden unexplained worsening of
9、 renal function;impairment of renal function secondary to antihypertensive treatment,particularly with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker;or renal dysfunction not attributable to another cause.Cardiac disturbance syndromes:recurrent flash pulmonary edema ou
10、t of proportion to any impairment of left ventricular function,or unstable angina in the setting of significant RAS.,Medical Therapy,control of blood pressure:ACE inhibitors or Angiotensin receptor blockers?antiplatelet therapysmoking cessationaggressive control of hyperlipidemia and DM The best med
11、ical therapy for ARVD remains unclear.Medical therapy hardly prevents renal function worsen in patients with bilateral RAS or RAS of single kidney.Chabova V,et al.Mayo Clin Proc 2000;75:437-444 Baboolal K Am J Kidney Dis 1998;31:971-977,肾动脉支架置入,meta-analysis data demonstrating superiority of renal a
12、rtery stent compared with balloon angioplasty for procedure success and restenosis rates,术前准备,阿斯匹林0.10.3 QD,氯吡格雷75mg QD，2-3天;降压,血压控制在160/100mmHg；碘过敏试验;,Endovascular Treatment of Renal Artery Stenoses,1.Through a femoral access,Emerald.035,.014 Stabilizer+6F Brite Tip Sheath 55cm,Endovascular Treatme
13、nt of Renal Artery Stenoses,2.Through a brachial access,Tempo 4F MP+.014 Stabilizer,Renal Artery Stenting,Case report-1,女，60岁，发现高血压2年，最高200/120mmHg。反复出现胸闷，夜间阵发性呼吸困难，不能平卧，双下肢浮肿。二型糖尿病10年。用药：蒙诺10mg Qd，波依定5mg Qd，寿比山2.5mg Qd，血压一般控制在150/90mmHg左右。血肌酐244umol/L,尿素氮22.9mmol/L,K+5.76mmol/L,GLU8.09mmol/L，尿（-）胸片
14、示双肺淤血，右侧少量胸腔积液，UCG示左房前后径45mm，左室舒张末期前后径61mm，EF43%冠脉造影（-）MRA 双肾动脉近段重度狭窄（90%）,GFR 左（min/l）右（min/l）术前 24.0 20.4术后（第3天)21.3 34.6,肾照相（99mTc-DTPA）,术后随访,拜新同30mg,Qd;阿托伐他丁10mg,Qn;阿斯匹林0.1,Qd;氯吡格雷75mg,Qd,1个月术后2周：Bp120/82mmHg,Cr125.4umol/L,BUN7.39mmol/L术后6个月：Bp132/86mmHg,Cr115umol/L,BUN6.2 mmol/L术后12个月：Bp128/84m
15、mHg,Cr118umol/L,BUN7.2 mmol/L术后18个月：Bp136/88mmHg,Cr128umol/L,BUN7.9 mmol/L,ARVD Randomized StudiesPTRA vs Medication,肾动脉支架的临床结果,文献汇总分析：肾功能：1/3 提高 1/3 不变 1/3恶化高血压：,治愈 改善FMD 50 85%85-100%ARAS 5 15%50 70%TA 40-60%75-90%,ASTRALAngioplasty and STent for Renal Artery LesionsUK MULTI-CENTRE TRIAL INATHEROS
16、CLEROTIC RENOVASCULAR DISEASE,Philip A KalraLead Nephrologist for ASTRAL,Hope Hospital,Salford,UK,On behalf of the ASTRAL TMC and collaborators,ASTRAL Trial:Design,Primary and secondary end points in ASTRAL,Rate of progression of renal dysfunction(using serum creatinine analysed by reciprocal creati
17、nine plots over time),Stent Med Rx p Value,Age 70 71 NSMale 63%63%NSDiabetes 31%29%NSCr 179 178 NSGFR 40 39 NSBilateral 50%50%NSACE/ARB 47%38%NS,Baseline Characteristics,ASTRAL:Lesion Severity,Mean=76%(Range:20%100%)Site reported:no core lab,No.of patients,Stenosis(%),ASTRAL:Treatment,Revascularizat
18、ion Strategies:Stenting 93%PTA alone 7%Post-stent residual stenosis 50%:12%Complications:7%Perforations:4(1%)Cholesterol Emboli 3(1%)Death 30 days of stent:2(0.5%),ASTRAL:Primary Endpoint,1/Cr,7.50,7.00,6.50,6.00,5.50,5.00,0,6,12,18,24,30,36,42,48,Revascularisation,Medical Management,Months from Ran
19、domisation 403 339 320 284 220 132 84 403 348 328 299 215 130 77,Revascularisation,Medical,P=ns,ASTRAL:Change in Systolic BP,P=ns,10,5,0,-5,-10,-15,-20,10,7,3,0,-3,-7,-10,6,12,18,24,30,36,42,48,6,12,18,24,30,36,42,48,Months from Randomisation,Revascularisation,Medical Management,Mean Change inSystol
20、ic BP,Treatment Difference,Revascularisation:384 330 315 274 216 137 83 Medical:388 341 327 290 211 127 81,ASTRAL Event Composite:MI,Stroke Vascular Death Hospitalization for Angina,Fluid Overload or CHF,以前的RCT研究,ASTRAL,经皮肾动脉成形联合药物治疗 优于单纯药物治疗,未能证明,支架+药物治疗,药物治疗,Effectiveness of Management Strategies
21、for Renal Artery Stenosis,质 疑-1,介入治疗经验和资质缺乏 ASTRAL:平均每个中心每年入选肾动脉支架术仅0.8例（369/58/8），支架技术成功率低(88%),质 疑-2,入选标准太宽，大部分病例的肾动脉狭窄不能肯定是否有功能意义.ASTRAL Trial:Design 1)with 1 ARVD lesion,and 2)in whom“substantial uncertainty about whether early revascularization is clinically indicated.In particular it should be
22、 unlikely that revascularization will become definitely indicated within the next 6 months.”,ASTRAL:Lesion Severity,Mean=76%(Range:20%100%)Site reported:no core lab,No.of patients,Stenosis(%),质 疑-3在流量大、介入标准严格的医疗中心采用肾动脉支架术治疗ARVD患者的非随机研究结果优于随机的支架治疗组。preserves renal function:Meta analysis,Medical thera
23、py Associated with progressive decline in renal functionStenting Beneficial effect on slope of 1/Cr“Stabilization”,Chabova Mayo Clin Proc 2000;75:437-44.Harden Lancet 1997;349:1133-1136.Watson Circ 2000;102:1671-7.,7,6,5,4,3,2,1,0,-600,-500,-400,-300,-200,-100,0,100,200,300,400,500,600,Serum creatin
24、ine,X10-3,药物治疗与介入治疗的随机对比研究可 靠 吗？,最大问题是方法学上的可比性差：药物治疗组在不同中心的质控可保持基本一致，但介入治疗组由于不同中心的研究团队水平差异，质控很难保持一致，对结果影响很大.,ASTRAL等随机临床研究的启示,1.单纯药物治疗不能阻止ARVD患者肾功能的恶化；2.肾动脉支架术的指征需要严格掌握，以避免无效治疗；3.肾动脉介入治疗与其它血管领域介入一样，需要经验和合格的资质，以提高手术成功率，防范介入对肾脏的直接损害。,经皮支架重建血运治疗粥样硬化性肾动脉狭窄的中远期临床结果,中国医学科学院 北京协和医学院 阜外心血管病医院 蒋雄京 杨倩 杨跃进 吴海英
25、 张慧敏 惠汝太 高润霖,有效？,无效？,本研究报告我院近5年来连续238例ARAS患者经皮支架置入重建肾动脉血运的中远期临床结果，对该问题作一探讨。,规模大、标准严的医疗中心经皮肾动脉支架术,资料与方法,本研究病例入选标准：(1)肾动脉主干或主要分支直径狭窄60%，如直径狭窄仅为60%75%，则必须具备狭窄远、近端压差30mmHg 或卡托普利肾图阳性(2)未服降压药时血压180/110 mmHg或正规三联降压药治疗血压140/90mmHg；(3)血肌酐7.0cm，并且残余的GFR10ml/min；(5)年龄30岁，性别不限。排除标准：(1)病情不稳定，无法耐受介入治疗；(2)造影剂过敏；(3
26、)肾动脉病变的解剖条件不适合进行介入治疗,结果-患者的基本临床特征,结果-患者的基本临床特征,PTRAS的造影和支架结果及并发症,238例患者中2例的2条肾动脉发生严重夹层，1例的1条分支血管被支架压闭，总的血运重建技术成功率99%(303/306)。PTRAS相关并发症总计5.5%(13/238).,结果-随访及失访情况,随访672(29.219.6)个月，共失访23例(9.7%),PTRAS对血压的影响,临床判定的支架内再狭窄率3.0%(7/238),PTRAS对肾功能的影响,PTRAS后血压和肾功能转归,36例术前肾功能异常的患者，PTRS后肾功能改善21例(77.8%)无变化9例(25
27、%)，恶化3例(8.3%)(其中2例发展至肾衰竭尿毒症期，已行透析治疗)，失访2例(5.6%)，死亡1例(2.7%)。,本研究PTRAS后的无事件生存率,Severity of renal vascular disease predicts mortality in patients undergoing CAGKidney International(2001)60,14901497,PTRAS后的心血管事件,共发生心血管事件24例(10.1%)，另有其他原因死亡4例。,随访期患者发生各种心血管事件的相关因素,Case 1:Bilateral renal artery stenoses in
28、 a aged 69 elderly with renal insufficiency,3 antihypertensive medications,BP 178/88mmHg,Cr 187 umol/l,Follow-upOne antihypertensive drug 3 days BP134/82mmHg,Cr132umol/l 14 days BP132/84mmHg,Cr118umol/l6 mons BP128/72mmHg,cr107umol/l12mons BP126/76mmHg,cr112umol/l,Male,61yr，Hypertension10yr，BP180/11
29、0mmHg with five antihypertensive medications.CHD,2 years ago LAD PCI,Smoking,Hyperlipidimia SCr 205umol/l3 days after procedure BP132/84mmHg with two antihypertensive medications SCr128umol/l24 months after procedure BP124/72 84mmHg with two antihypertensive medications SCr116umol/l,64-slices CTA fi
30、nding on a female,65 yo.High blood pressure 20 years,Maximal BP 210/120mmHG,out of control with nifedipine IGTS 30mg qd,bisoprolol 5mg qd,and perindopril 4mg qd,for 5 years,Exacerbate 3m,结论,我们的单中心研究表明支架置入重建血运治疗粥样硬化性肾动脉严重狭窄有较好的安全性，中远期降压和稳定肾功能的获益肯定。本研究也提示肾动脉支架术有可能显著减少心血管事件的发生率并降低死亡率，但还需要进一步研究予以证实。,阜外医
31、院肾动脉狭窄研究的现状,1999-至今已积累550例肾动脉介入病例。近年来新来我院诊治的肾动脉狭窄患者300例/年以上，实施介入治疗病例150例/年，欧美国家达到如此规模的医学中心不到5家。,肾动脉介入治疗的现状,以肾功能不全的进展率为主要终点事件的研究，如果要取得阳性结果，则需要满足二个关键点：,1.病例入选要严格，即双侧或单功能肾的肾动脉严重狭窄（70%）所致的缺血性肾病。对于单侧肾动脉狭窄,患肾较对照侧肾功能下降至少25%。2.从事肾动脉介入的治疗团队富有经验，能有效防范介入对肾脏直接损害。,以控制高血压为目的的肾动脉支架术,如果入选标准定在肾动脉直径狭窄50%，可能包括部分没有血流动力
32、学意义的狭窄(50-70%)，肾动脉支架术不但无效，而且要承担介入治疗本身的风险。实践表明，入选患者要满足二个关键点：1.肾动脉狭窄70%，且能证明狭窄与高血压存在因果关系；2.顽固性高血压或不用降压药高血压达III级水平。,如何保证肾动脉支架术疗效?,1.严格把握肾动脉介入的适应征2.防范介入对肾脏的直接损害，提高手术成功率。,肾动脉支架术后急性肾功能损害的主要原因,1.介入操作过程中发生的肾动脉栓塞 及其它损伤；2.造影剂诱发的肾毒性；3.血容量不足导致的肾灌注不足。,重视控制危险因素,ARVD是全身动脉粥样硬化的一部分，肾动脉支架术成功并不意味着动脉粥样硬化进程的终止。降脂治疗、降糖治疗
33、、降压治疗及阿斯匹林等对防止动脉粥样硬化发展有深远的影响，对预防心血管并发症有重大意义，应予高度重视。,纤维肌性结构不良(FMD)及大动脉炎所致的肾动脉狭窄,PTA的指征相对宽松：1.肾动脉狭窄50%;2.持续高血压160/100mmHg大动脉炎活动期不宜手术，一般要用糖皮质激素治疗使血沉降至正常范围后2个月以上方可考虑行PTA 一般不使用血管内支架,仅作为PTA失败的补救措施:1.单纯PTA治疗FMD及大动脉炎的结果很好;2.这类病变放置支架远期结果并清楚。,Clinical outcomes of PTRA as Treatment for Renal Artery Stenosis ca
34、used by aortoarteritis or FMD,Jiang Xiongjing,et al.Hypertension Division,Cardiovascular Institute and Fu Wai Hospital,CAMS and PUMC,METHODPatients selection for PTRA,In presence of renal artery 60%diameter stenosis,Patients had Poorly controlled hypertension while receiving 3 antihypertensive medic
35、ations or HBP grade III without antihypertensive medications.a.Increased renal vein renin b.Captopril Renoscitigraphy Positive c.serum creatinine level30%residual stenosis after PTA e.Longitudinal kidney length 7.0cm with GFR10ml/minIndications for inclusion were not mutually exclusive.,Clinical cha
36、racteristics of 80 study patients,GENDER(m/f)28/52AGE(YR)1358(29 14)ETIOLOGY(N)FIBROMUSCULAR DYSPLASIA 18(22.5%)ARTERITIS 62(77.5%)Lesions stenoses(%)60%100%(82 15),Blood pressure response(SBP/DBP,mmHg)after PTRA,baseline discharge 6month Arteritis 174.532.8/106.820.4 129.221.6/80.211.5*134.625.3/83
37、.413.6*#FMD 156.426.8/104.612.4 126.415.2/75.69.8*128.817.6/76.210.4*No.of med 2.91.3 1.01.1*1.21.4*#*P0.001compared with baseline.#P0.05 compared with values at discharge.SBP=systolic blood pressure;DBP=diastolic blood pressure,The effect of PTRA on hypertension at 6-month follow-up,Etiology Cure(%
38、)Improved(%)No improvement(%)Total(%)Arteritis 35(56.5)19(30.6)8(12.9)62(100)FMD 14(77.8)3(16.7)1(5.6)18(100)Cure:SBP10%or DBP15%with taking same medications,SBP10%or DBP15%with taking fewer medications;No improvement:the aforementioned criteria were not met.Estimated restenosis rate:8 pts with arte
39、ritis&1 pts with FMD,The serum Creatinine and Blood Urea Nitrogen response after PTRA,Renal function Baseline discharge 6-month Cr（umol/L）96.811.2 102.1 16.8#94.2 9.9 BUN（mmol/L）6.11.8 6.31.3#6.01.6#P0.05 compared with baselineDuring follow-up normal renal function remains in all patients,Conclusion
40、,PTRA is appropriate for such patients when there is good evidence of a potentially hemodynamically significant RAS.Stenting should be considered in case of suboptimal result or PTA failure.,Conclusion,Based on the available data,One thing appears certain:no one therapeutic approach is appropriate f
41、or all patients.In each patient,the individual risks and benefits associated with each potential treatment needs to be considered.Percutaneous intervention should be undertaken when there is good evidence of a potentially hemodynamically significant RAS.,Female,68yo,HT,随访&预 后,本病为慢性进行性血管病变。对所有TA患者均需要进行大血管影像学检查及长期随访,动态观察动脉受累情况。预后主要取决于高血压的程度及重要脏器的累及情况。受累后的动脉一般侧支循环形成丰富，故发生脏器缺血坏死少见。糖皮质激素或联合免疫抑制剂积极治疗可改善预后,但减量或停药有复发可能。血管重建能改善缺血，但远期有一定的再狭窄率。,Thanks,
