高血壓合并腎損害的處理

1、高血壓合并腎損害的處理,初少莉上海交大醫(yī)學(xué)院 附屬瑞金醫(yī)院上海市高血壓研究所、高血壓科,概述 高血壓伴CKD的處理,內(nèi) 容,高血壓與主要器官間的關(guān)系,CKD主要原因之一,高血壓,50%-75%CKD,美國(guó)CKD患病率(AJKD 2004,人群（10萬(wàn),National kidney foundation K/DOQI guideline Am J Kidney Dis. 2004:Suppt.1-234,30,40,76,53,59,15,GFR(ml/min,15-29,30-59,60-89,90,中國(guó)CKD流行病學(xué)資料,1余學(xué)清等,中華腎臟病雜志,2007,23(3)147-151 2張

2、路霞等,中華腎臟病雜志,2006,22(2)69-71 3張路霞等,中華腎臟病雜志,2007,23(3)152-155,CKD在不同人群中的患病率(,Early detection and intervention of CKD and associated factors in Beijing,15.9,20.7,9.3,Incident Rates by Primary Diagnosis,US Renal Data System.USRDS 2000 Annual Data Report.Bethesda,MD:National Institutes of Health;2000,校正的

3、風(fēng)險(xiǎn)比（所有原因死亡 心血管事件 任何原因住院的,校正年齡,收入,教育,腎透析,冠心病,慢性心衰,缺血性卒中,TIA,PAD,DM,HT,DL,腫瘤,癡呆,慢性肝病,慢性肺病,蛋白尿,住院. Go AS et al.N Engl J Med .2004;351:1296-1305,高血壓增加心血管病與腎臟病的危險(xiǎn),Am J Hypertens 2000,13:3S-10S Hypertension 1995,25:587-594 N Engl J.Med. 1996,334:13-18,控制血壓 保護(hù)腎臟,減少有效腎單位,增加腎小球 內(nèi)壓,腎硬化與纖維化,腎小球肥厚,高血壓,Wang H.Y

4、in APCC,高血壓伴CKD患者增加心血管危險(xiǎn)的可能機(jī)制,同型半胱酸增加 交感活性增加 血漿非對(duì)稱性二甲基精氨酸（asymmetric dimethylarginine , ADMA) 濃度增高 血管鈣化的危險(xiǎn)性增加,Updatared from Zoccali C.Kidney Int.2006;70:26-33,概述 高血壓伴CKD的處理,內(nèi) 容,CKD的處理以抗高血壓治療為主的綜合干預(yù),非藥物治療: 改善生活方式及?？频臓I(yíng)養(yǎng)治療 藥物治療: 抗高血壓藥物治療 降壓目標(biāo) 降壓藥物的選擇 聯(lián)合治療 多重危險(xiǎn)因素的控制（調(diào)脂、抗血小板等,CKD患者均應(yīng)進(jìn)行抗高血壓治療,降壓 降低心血管病的危

5、險(xiǎn)(不論是否有高血壓) 延緩腎臟病進(jìn)展(不論是否有高血壓,National kidney foundation K/DOQI guideline Am J Kidney Dis. 2004:Suppt.1-234,降壓目標(biāo)： CKD為心血管病的極高危因素，治療要兼顧延緩腎功能不全進(jìn)展及降低心血管病危險(xiǎn)： 1、嚴(yán)格控制血壓 (1g/日可更低) 2、降低蛋白尿，使其盡可能恢復(fù)正常,抗高血壓藥物的選擇與應(yīng)用,選擇的原則： 遵循指南 堅(jiān)持個(gè)化治療 首選藥物: （兼有降壓、降蛋白尿、延緩GFR降低,各主要權(quán)威指南,ESC/ESH(2007) ACEI or ARB ADA (2004) ACEI or

6、ABR NKF:DOQI-BP(2004) ACEI or ABR KDQI-CKD(2002) ACEI or ABR JNC7（2003） ACEI or ABR CHINA(2005) ACEI or ARB CANADIAN (2002) ACEI or ABR WHO/ISH(1999) ACEI,兼有降壓、降蛋白尿、延緩GFR降低,對(duì)CKD患者治療ACEI vs ARB 孰優(yōu)孰劣,Head-to-head trials Hypertension 0 Diabetes type 1 0 type 2 0 with nephropathy 0 Post MI (heart failur

7、e) OPTIMAAL, VALIANT Chronic Heart Failure ELITE II Pervention of disease progression 0 High CV risk Ontarget,Hypertension with CKD 0,ONTARGET The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial WWW.NEJM.ORG ON MARCH 31,2008 N ENGL J MED, 2008;358:1547-1559,ONTARGET,

8、Questions: 1. Is telmisartan “non-inferior” to ramipril ? 2. Is the combination superior to ramipril ? Outcome: Primary: CV death, MI, stroke, CHF hosp Key secondary: CV death, MI, stroke (HOPE trial outcome) Design: Single blind run-in (n=29,019) Randomized, double blind, double dummy study conduct

9、ed in 733 centers in 40 countries (n=25,620) 56 months follow-up with 99.8% outcome ascertainment,Change in BP (mmHg,Time to Primary Outcome,ONTARGET,Primary Outcome 45:880-886,Time to Primary Outcome（ARB與ACEI聯(lián)合,ONTARGET,Tel + Ram,Ram alone,Reasons for Permanently Stopping Study Medications,ONTARGET

10、,結(jié) 論（Tel plus Ram vs. Ram,1. Tel與Ram聯(lián)合較Ram單用，并未更大程 度降低主次要終點(diǎn)，提示聯(lián)合并不優(yōu)于單用； 2. 聯(lián)合較單用ACEI增加不良事件,ONTARGET,期待對(duì)于CKD患者的亞組分析結(jié)果,不同聯(lián)合方案的比較,聯(lián)合CCB vs 聯(lián)合利尿藥,迄今，無(wú)針對(duì)CKD的聯(lián)合治療方案頭對(duì)頭臨床試驗(yàn),HOT研究腎臟病患者亞組數(shù)據(jù)分析證實(shí)非洛地平降壓達(dá)標(biāo)效果好,血壓治療前隨訪 624終點(diǎn) 低SBP (mmHg)170 15142 15141 14 141 15 高17217144 16141 17141 17 低DBP (mmHg)105 484 783 7 83

11、7 高106 485 882 8 82 9,血清肌 酐水平,Hypertension Unit. J Am Soc Nephrol 2001; 12: 218-25,HOT研究 腎臟病患者亞組數(shù)據(jù)分析證實(shí)非洛地平 對(duì)腎功能無(wú)不良影響,Hypertension Unit. J Am Soc Nephrol 2001; 12: 218-25,Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension,Targeted Population for R

12、ecruitment into the ACCOMPLISH Study,Men or women age 55 years SBP 160 mmHg or currently on antihypertensive therapy Evidence of cardiovascular or renal disease or target organ damage,DSMB Oct 17 2007,Pre-specified efficacy boundary was crossed with 60% of the expected trial information Executive Co

13、mmittee accepted the recommendation Last patient last visit was Jan 24, 2008 Total of 1176 unique patients with events 95.3% of primary events are adjudicated,Systolic Blood Pressure Over Time,mm Hg,Month,57315387520649994804428525201045 57095377515449804831428625941075,Patients,Mean values are take

14、n at 30 months F/U visit,129.3 mmHg,130mmHg,Difference of 0.7 mmHg p0.05,DBP: 71.1,DBP: 72.8,差1.7mmHg,37.2,37.9,ACCOMPLISH: Exceptional Control Rates with Initial Combination Therapy,ACEI / HCTZ N=5733,Control rate (,CCB / ACEI N=5713,10,20,30,40,50,60,70,80,90,P0.001 at 30 months follow-up,Control

15、defined as 140/90 mmHg,Kaplan Meier for Primary Endpoint,Cumulative event rate,HR (95% CI): 0.80 (0.72, 0.90,Time to 1st CV morbidity/mortality (days,p = 0,650,526,0,0,0,2,INTERIM RESULTS Mar 08,提 示,聯(lián)合治療可獲得非常好的血壓控制； 2. 初始 ACEI / CCB優(yōu)于ACEI/DD的聯(lián)合治療，這對(duì)以DD作為降壓基礎(chǔ)治療的觀點(diǎn)提出挑戰(zhàn),Initial combinations of Medications,diuretics,ACEI or ARB,CCB,利尿治療的利弊,利尿藥,抑腎臟鈉（鎂）重吸收,低鎂血癥,低鈉血癥