腎血管病的處理

1、Management of Renovascular Hypertension,阜外心血管病醫(yī)院心內(nèi)科蔣雄京,Interrelation among Renal Artery Stenosis, Hypertension, and Chronic Renal Failure,Definition of Renal Artery StenosisRenal artery stenosis (RAS) is defined as na

2、rrowing of the lumen of the renal artery. *angiographic diameter stenosis>50%*translesional pressure gradient of >20 mm Hg peak systolic or 10 mm Hg mean The most common causes of RAS are atherosclerosis

3、(>80%) , aortoarteritis(<15%), and fibromuscular dysplasia(<5%) in China,Angiographic Appearance of the Three Common Forms of Renal Artery Stenosis,Prevalence,1. 1~3% in hypertensive population2. 20~30% in pa

4、tients with secondary hypertension,Incidence of Renal Artery Stenosis at Cardiac Catheterization,Authors Year Country Patients Age CAD (%) HT (%) RAS (%)Crowley 1998 USA

5、 14152 61 89 72 6.3Conlon 2000 Ireland 3987 52 100 58 6.3Weber 2002 Austria 177

6、 63 62 67 11Yamashita 2002 Japan 289 66 76 48 7Rihal 2002 USA 297 65 NA

7、 100 19.2Buller 2004 Canada 837 67 68 32 14.3Addad 2005 Tunisia 300 58 100 35

8、 9CAD = Coronary artery disease; HTN = Hypertension; RAS = significant renal artery stenosis; NA = nonavailable.,Incidence of Renal Artery Stenosis at Cardiac Catheterizationin Chinese population,,,,Progress

9、ive Atherosclerosis, Renal Artery Stenosis, and Ischemic Nephropathy,the clinical manifestations of ARVD,Clinical features suggestive of renovascular hypertensionJNC-VI,Onset of hypertension aged<30 y;Abdominal brui

10、t;Accelerated or resistant hypertension;Flash pulmonary edema with normal left ventricular function;Renal failure of uncertain cause;Coexisting, diffuse atherosclerotic vascular diseaseAcute renal failure precipitat

11、e 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,1 .Radionuclide renal fract

12、ional 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 di

13、sease predicts mortality in patients undergoing coronary angiographyKidney International (2001) 60, 1490–1497,Clinical Criteria for Revascularization,Hypertension: accelerated hypertension; refractory hypertension; mali

14、gnant hypertension; hypertension with a unilateral small kidney; or hypertension with intolerance to medication. Renal salvage: sudden unexplained worsening of renal function; impairment of renal function secondary to a

15、ntihypertensive treatment, particularly with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker; or renal dysfunction not attributable to another cause. Cardiac disturbance syndromes: recurren

16、t "flash" pulmonary edema out 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 Ang

17、iotensin receptor blockers ?antiplatelet therapysmoking cessationaggressive control of hyperlipidemia and DM The best medical therapy for ARVD remains unclear. Medical therapy hardly prevents renal function wor

18、sen 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,腎動(dòng)脈支架置入,meta-analysis data demonstrating super

19、iority of renal artery stent compared with balloon angioplasty for procedure success and restenosis rates,術(shù)前準(zhǔn)備,阿斯匹林0.1~0.3 QD, 氯吡格雷75mg QD ，2-3天;降壓,血壓控制在<160/100mmHg；碘過(guò)敏試驗(yàn);,Endovascular Treatment of Renal Artery Ste

20、noses,1.Through a femoral access,,Emerald .035,.014 Stabilizer + 6F Brite Tip Sheath 55cm,Endovascular Treatment of Renal Artery Stenoses,2. Through a brachial access,Tempo 4F MP + .014 Stabilizer,Renal Artery Stenting,C

21、ase report -1,女，60歲，發(fā)現(xiàn)高血壓2年，最高200/120mmHg。反復(fù)出現(xiàn)胸悶，夜間陣發(fā)性呼吸困難，不能平臥，雙下肢浮腫。二型糖尿病10年。用藥：蒙諾10mg Qd，波依定5mg Qd，壽比山2.5mg Qd，血壓一般控制在150/90mmHg左右。血肌酐244umol/L,尿素氮22.9mmol/L,K+5.76mmol/L, GLU8.09mmol/L，尿（-）胸片示雙肺淤血，右側(cè)少量胸腔積液，UCG示左房

22、前后徑45mm，左室舒張末期前后徑61mm，EF43% 冠脈造影（-）MRA 雙腎動(dòng)脈近段重度狹窄（>90%）,GFR 左（min/l） 右（ min/l ）術(shù)前 24.0 20.4術(shù)后（第3天) 21.3 34.6,腎γ照相（99mTc-DTPA）,術(shù)后

23、隨訪,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個(gè)月術(shù)后2周 ：Bp120/82mmHg,Cr125.4umol/L,BUN7.39mmol/L術(shù)后6個(gè)月 ：Bp132/86mmHg,Cr115umol/L,BUN6.2 mmol/L術(shù)后12個(gè)月：Bp128/84mmHg,Cr118umol/L,BUN7.2 mmol/L術(shù)后18個(gè)月：Bp136/88mmHg,Cr

24、128umol/L,BUN7.9 mmol/L,ARVD – Randomized StudiesPTRA vs Medication,腎動(dòng)脈支架的臨床結(jié)果,文獻(xiàn)匯總分析：腎功能： 1/3 提高 1/3 不變 1/3惡化高血壓：,治愈 改善FMD 50 – 85% 85 - 100%ARAS

25、 5 – 15% 50 – 70%TA 40 - 60% 75 - 90%,,,,,,ASTRALAngioplasty and STent for Renal Artery LesionsUK MULTI-CENTRE TRIAL INATHEROSCLEROTIC RENOVASCULAR DIS

26、EASE,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 d

27、ysfunction (using serum creatinine analysed by reciprocal creatinine plots over time),Stent Med Rx p Value,Age 70 71 NSMale 6

28、3% 63% NSDiabetes 31% 29% NSCr 179 178 NSGFR 40 39 NS

29、Bilateral 50% 50% NSACE/ARB 47% 38% NS,,,,Baseline Characteristics,,ASTRAL: Lesion Severity,Mean = 76% (Range: 20% –100%)Site reported: no co

30、re lab,No. of patients,Stenosis(%),ASTRAL: Treatment,Revascularization Strategies:?Stenting 93% ?PTA alone 7%?Post-stent residu

31、al stenosis > 50%: 12%?Complications: 7% – Perforations: 4 (1%) – Cholesterol Emboli 3 (1%) – Death <

32、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

33、,Medical Management,Months from Randomisation 403 339 320 284 220 132 84 403 348 328 299

34、 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

35、,-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 inSystolic BP,Treatment Difference,Revascularisation: 384 33

36、0 315 274 216 137 83 Medical: 388 341 327 290 211 127 81,ASTRAL Event Com

37、posite: MI, Stroke Vascular Death Hospitalization for Angina, Fluid Overload or CHF,以前的RCT研究,ASTRAL,,,經(jīng)皮腎動(dòng)脈成形聯(lián)合藥物治療 優(yōu)于單純藥物治療,未能證明,,支架+藥物治療,藥物治療,Effectiveness of Management Strategies for Renal Artery Stenosis,質(zhì)

38、疑-1,介入治療經(jīng)驗(yàn)和資質(zhì)缺乏 ASTRAL:平均每個(gè)中心每年入選腎動(dòng)脈支架術(shù)僅0.8例（369/58/8），支架技術(shù)成功率低(88%),質(zhì) 疑-2,入選標(biāo)準(zhǔn)太寬，大部分病例的腎動(dòng)脈狹窄不能肯定是否有功能意義. ASTRAL Trial: Design 1) with ≥ 1 ARVD lesion, and 2) in whom “substantial uncertainty about whethe

39、r early revascularization is clinically indicated. In particular it should be unlikely that revascularization will become definitely indicated within the next 6 months.”,ASTRAL: Lesion Severity,Mean = 76% (Range: 20% –10

40、0%)Site reported: no core lab,No. of patients,Stenosis(%),質(zhì) 疑-3在流量大、介入標(biāo)準(zhǔn)嚴(yán)格的醫(yī)療中心采用腎動(dòng)脈支架術(shù)治療ARVD患者的非隨機(jī)研究結(jié)果優(yōu)于隨機(jī)的支架治療組。 preserves renal function: Meta analysis,?Medical therapy Associated with progressive decline in re

41、nal function?Stenting 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,,,,,,,,,,,

42、,,-600,,-500,-400,-300,-200,-100,0,100,200,300,400,500,600,,,,,,,,,,,,,,,,,,,,,,,,,,,,Serum creatinine,X10-3,藥物治療與介入治療的隨機(jī)對(duì)比研究可 靠 嗎 ？,最大問(wèn)題是方法學(xué)上的可比性差： 藥物治療組在不同中心的質(zhì)控可保持基本一致，但介入治療組由于不同中心的研究團(tuán)隊(duì)水平差異，質(zhì)控很難保持一致，對(duì)結(jié)果影響很大.,ASTRA

43、L等隨機(jī)臨床研究的啟示,1. 單純藥物治療不能阻止ARVD患者腎功能的惡化；2. 腎動(dòng)脈支架術(shù)的指征需要嚴(yán)格掌握，以避免無(wú)效治療；3. 腎動(dòng)脈介入治療與其它血管領(lǐng)域介入一樣，需要經(jīng)驗(yàn)和合格的資質(zhì)，以提高手術(shù)成功率，防范介入對(duì)腎臟的直接損害。,經(jīng)皮支架重建血運(yùn)治療粥樣硬化性腎動(dòng)脈狹窄的中遠(yuǎn)期臨床結(jié)果,中國(guó)醫(yī)學(xué)科學(xué)院 北京協(xié)和醫(yī)學(xué)院 阜外心血管病醫(yī)院 蔣雄京 楊倩 楊躍進(jìn) 吳海英 張慧敏 惠汝太 高潤(rùn)霖,有效？,無(wú)效？,本研究報(bào)告我院

44、近5年來(lái)連續(xù)238例ARAS患者經(jīng)皮支架置入重建腎動(dòng)脈血運(yùn)的中遠(yuǎn)期臨床結(jié)果，對(duì)該問(wèn)題作一探討。,規(guī)模大、標(biāo)準(zhǔn)嚴(yán)的醫(yī)療中心經(jīng)皮腎動(dòng)脈支架術(shù),資料與方法,本研究病例入選標(biāo)準(zhǔn)：(1)腎動(dòng)脈主干或主要分支直徑狹窄≥60%，如直徑狹窄僅為60%~75%，則必須具備狹窄遠(yuǎn)、近端壓差≥30mmHg 或卡托普利腎圖陽(yáng)性(2)未服降壓藥時(shí)血壓>180/110 mmHg或正規(guī)三聯(lián)降壓藥治療血壓>140/90mmHg；(3)血肌酐7.0c

45、m，并且殘余的GFR>10ml/min；(5)年齡≥30歲，性別不限。排除標(biāo)準(zhǔn)：(1)病情不穩(wěn)定，無(wú)法耐受介入治療；(2)造影劑過(guò)敏；(3)腎動(dòng)脈病變的解剖條件不適合進(jìn)行介入治療,結(jié)果-患者的基本臨床特征,結(jié)果-患者的基本臨床特征,PTRAS的造影和支架結(jié)果及并發(fā)癥,238例患者中2例的2條腎動(dòng)脈發(fā)生嚴(yán)重夾層，1例的1條分支血管被支架壓閉，總的血運(yùn)重建技術(shù)成功率99%(303/306)。PTRAS相關(guān)并發(fā)癥總計(jì)5.5

46、%(13/238).,結(jié)果-隨訪及失訪情況,,隨訪6～72(29.2±19.6)個(gè)月，共失訪23例(9.7%),PTRAS對(duì)血壓的影響,臨床判定的支架內(nèi)再狹窄率3.0%(7/238),PTRAS對(duì)腎功能的影響,PTRAS后血壓和腎功能轉(zhuǎn)歸,36例術(shù)前腎功能異常的患者，PTRS后腎功能改善21例(77.8%)無(wú)變化9例(25%) ，惡化3例(8.3%)(其中2例發(fā)展至腎衰竭尿毒癥期，已行透析治療)，失訪2例(5.6%) ，死

47、亡1例(2.7%)。,本研究PTRAS后的無(wú)事件生存率,Severity of renal vascular disease predicts mortality in patients undergoing CAGKidney International (2001) 60, 1490–1497,PTRAS后的心血管事件,共發(fā)生心血管事件24例(10.1%)，另有其他原因死亡4例。,隨訪期患者發(fā)生各種心血管事件的相關(guān)因素,,,Cas

48、e 1: Bilateral renal artery stenoses in 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

49、14 days BP132/84mmHg,Cr118umol/l6 mons BP128/72mmHg,cr107umol/l12mons BP126/76mmHg,cr112umol/l,Male, 61yr，Hypertension>10yr，BP180/110mmHg with five antihypertensive medications. CHD, 2 years ago LAD PCI

50、, 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 medic

51、ations SCr116umol/l,64-slices CTA finding 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

52、5 years, Exacerbate 3m,結(jié)論,我們的單中心研究表明支架置入重建血運(yùn)治療粥樣硬化性腎動(dòng)脈嚴(yán)重狹窄有較好的安全性，中遠(yuǎn)期降壓和穩(wěn)定腎功能的獲益肯定。本研究也提示腎動(dòng)脈支架術(shù)有可能顯著減少心血管事件的發(fā)生率并降低死亡率，但還需要進(jìn)一步研究予以證實(shí)。,阜外醫(yī)院腎動(dòng)脈狹窄研究的現(xiàn)狀,1999-至今已積累550例腎動(dòng)脈介入病例。近年來(lái)新來(lái)我院診治的腎動(dòng)脈狹窄患者300例/年以上，實(shí)施介入治療病例>150例/年，歐美國(guó)

53、家達(dá)到如此規(guī)模的醫(yī)學(xué)中心不到5家。,腎動(dòng)脈介入治療的現(xiàn)狀,以腎功能不全的進(jìn)展率為主要終點(diǎn)事件的研究，如果要取得陽(yáng)性結(jié)果，則需要滿足二個(gè)關(guān)鍵點(diǎn)：,1.病例入選要嚴(yán)格，即雙側(cè)或單功能腎的腎動(dòng)脈嚴(yán)重狹窄（>70%）所致的缺血性腎病。對(duì)于單側(cè)腎動(dòng)脈狹窄,患腎較對(duì)照側(cè)腎功能下降至少>25% 。2. 從事腎動(dòng)脈介入的治療團(tuán)隊(duì)富有經(jīng)驗(yàn)，能有效防范介入對(duì)腎臟直接損害。,以控制高血壓為目的的腎動(dòng)脈支架術(shù),如果入選標(biāo)準(zhǔn)定在腎動(dòng)脈直徑狹窄?5

54、0%，可能包括部分沒(méi)有血流動(dòng)力學(xué)意義的狹窄(50-70%)，腎動(dòng)脈支架術(shù)不但無(wú)效，而且要承擔(dān)介入治療本身的風(fēng)險(xiǎn)。實(shí)踐表明，入選患者要滿足二個(gè)關(guān)鍵點(diǎn)：1. 腎動(dòng)脈狹窄?70%，且能證明狹窄與高血壓存在因果關(guān)系；2. 頑固性高血壓或不用降壓藥高血壓達(dá)III級(jí)水平。,如何保證腎動(dòng)脈支架術(shù)療效?,1.嚴(yán)格把握腎動(dòng)脈介入的適應(yīng)征2.防范介入對(duì)腎臟的直接損害，提高手術(shù)成功率。,腎動(dòng)脈支架術(shù)后急性腎功能損害的主要原因,1. 介入操作過(guò)程中發(fā)

55、生的腎動(dòng)脈栓塞 及其它損傷；2. 造影劑誘發(fā)的腎毒性；3. 血容量不足導(dǎo)致的腎灌注不足。,重視控制危險(xiǎn)因素,ARVD是全身動(dòng)脈粥樣硬化的一部分，腎動(dòng)脈支架術(shù)成功并不意味著動(dòng)脈粥樣硬化進(jìn)程的終止。降脂治療、降糖治療、降壓治療及阿斯匹林等對(duì)防止動(dòng)脈粥樣硬化發(fā)展有深遠(yuǎn)的影響，對(duì)預(yù)防心血管并發(fā)癥有重大意義，應(yīng)予高度重視。,纖維肌性結(jié)構(gòu)不良(FMD)及大動(dòng)脈炎所致的腎動(dòng)脈狹窄,PTA的指征相對(duì)寬松 ：

56、 1.腎動(dòng)脈狹窄>50%; 2.持續(xù)高血壓>160/100mmHg大動(dòng)脈炎活動(dòng)期不宜手術(shù)，一般要用糖皮質(zhì)激素治療使血沉降至正常范圍后2個(gè)月以上方可考慮行PTA 一般不使用血管內(nèi)支架, 僅作為PTA失敗的補(bǔ)救措施 : 1.單純PTA治療FMD及大動(dòng)脈炎的結(jié)果很好; 2.這類病變放置支架遠(yuǎn)期結(jié)果并清楚。,Clinical outcomes of PTRA as Treat

57、ment for Renal Artery Stenosis caused 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

58、 renal artery >60% diameter stenosis,Patients had Poorly controlled hypertension while receiving 3 antihypertensive medications or HBP grade III without antihypertensive medications. a. Increased renal vein renin

59、b. Captopril Renoscitigraphy Positive c. serum creatinine level30% residual stenosis after PTA e. Longitudinal kidney length > 7.0cm with GFR>10ml/minIndications for inclusion were not mutually exclusive.,Clin

60、ical characteristics of 80 study patients,GENDER(m/f) 28/52AGE(YR) 13~58 (29 ?14) ETIOLOGY(N)

61、 FIBROMUSCULAR DYSPLASIA 18(22.5%) ARTERITIS 62 (77.5%)Lesions stenoses(%)

62、 60%~100% (82 ?15),Blood pressure response (SBP/DBP, mmHg) after PTRA,baseline discharge 6month Arteritis 174.5±32.8/ 106.8±20.4 129.2±21.6/80.2&

63、#177;11.5* 134.6±25.3/83.4±13.6 *#FMD 156.4±26.8/ 104.6±12.4 126.4±15.2/75.6±9.8* 128.8±17.6/76.2±10.4 * No.of med 2.9±1.3

64、 1.0±1.1 * 1.2±1.4*# *P<0.001compared with baseline. # P<0.05 compared with values at discharge. SBP= systolic blood pressure; DBP=diastolic blood pressure,The effect

65、 of PTRA on hypertension at 6-month follow-up,Etiology Cure(%) Improved(%) No improvement(%) Total (%) Arteritis 35(56.5) 19 (30.6) 8(12.9) 62 (100) FMD

66、 14 (77.8) 3 (16.7) 1 (5.6) 18 (100) Cure:SBP10% or DBP?>15% with taking same medications, SBP?<10% or DBP?<15% with taking fewer medications; No improvemen

67、t: the aforementioned criteria were not met.Estimated restenosis rate: 8 pts with arteritis & 1 pts with FMD,The serum Creatinine and Blood Urea Nitrogen response after PTRA,Renal function Baseline

68、 discharge 6-month Cr （umol/L） 96.8±11.2 102.1 ±16.8# 94.2 ±9.9 BUN（mmol/L） 6.1±1.8 6.3±1.3#

69、 6.0±1.6 #P<0.05 compared with baselineDuring follow-up normal renal function remains in all patients,Conclusion,PTRA is appropriate for such patients when there is good evidence of a potentially hemodynamical