高血压合并肾损害的处理标准课件

概述概述高血压伴高血压伴CKD的处理的处理 内内 容容概述内 容1高血压与主要器官间的关系CKD主要原因之一主要原因之一高血压高血压50%-75%CKD高血压与主要器官间的关系CKD主要原因之一高血压50%-752美国美国CKD患病率患病率(AJKD 2004)人群（人群（10万）万）National kidney foundation K/DOQI guideline Am J Kidney Dis.2004:Suppt.1-234304076535915GFR(ml/min)15-2930-5960-8990 美国CKD患病率(AJKD 2004)人群（10万）Nat3中国中国CKD流行病学资料流行病学资料地区地区人群人群例数例数蛋白尿蛋白尿CKD广州广州1北京北京2浙江浙江3上海上海*20岁岁40岁岁18岁岁原高原高(住院住院)2213 240077051689.7(6.2)7.610.3(10.4)-16.1(10.1)11.013.510.6(3期期)1余学清等余学清等,中华肾脏病杂志中华肾脏病杂志,2007,23(3)147-1512张路霞等张路霞等,中华肾脏病杂志中华肾脏病杂志,2006,22(2)69-713张路霞等张路霞等,中华肾脏病杂志中华肾脏病杂志,2007,23(3)152-155中国CKD流行病学资料地区人群例数蛋白尿CKD广州1 204CKD在不同人群中的患病率(%)Early detection and intervention of CKD and associated factors in Beijing15.920.79.3CKD在不同人群中的患病率(%)Early detectio5Incident Rates by Primary DiagnosisUS Renal Data System.USRDS 2000 Annual Data Report.Bethesda,MD:National Institutes of Health;2000.Incident Rates by Primary Diag6校正的风险比校正的风险比（所有原因死亡（所有原因死亡 心血管事件心血管事件 任何原因住院的）任何原因住院的）N=1,120,295,Ambulatory Adults According to the eGFReGFR*所有原因死亡所有原因死亡CV事件事件任何原因住院任何原因住院Adjusted Hazard Ratio(95%Cl)=60ml/min/1.73m21.001.001.0045-59ml/min/1.73m21.2(1.1-1.2)1.4(1.4-1.5)1.1(1.1-1.1)30-44ml/min/1.73m21.8(1.7-1.9)2.0(1.9-2.1)1.5(1.5-1.5)15-29ml/min/1.73m23.2(3.1-3.4)2.8(2.6-2.9)2.1(2.0-2.2)15ml/min/1.73m25.9(5.4-6.5)3.4(3.1-3.8)3.1(3.0-3.3)*校正年龄校正年龄,收入收入,教育教育,肾透析肾透析,冠心病冠心病,慢性心衰慢性心衰,缺血性卒中缺血性卒中,TIA,PAD,DM,HT,DL,肿瘤肿瘤,痴呆痴呆,慢性慢性肝病肝病,慢性肺病慢性肺病,蛋白尿蛋白尿,住院住院.Go AS et al.N Engl J Med.2004;351:1296-1305校正的风险比（所有原因死亡 心血管事件 任何原因住院的）N7高血压增加心血管病与肾脏病的危险疾病疾病疾病疾病 相对危险相对危险相对危险相对危险(RR)(RR)肾衰肾衰肾衰肾衰(ESRD)2.8(ESRD)2.8卒中卒中卒中卒中 2.72.7心衰心衰心衰心衰 1.51.5心梗心梗心梗心梗 1.6 1.6 周围血管病周围血管病周围血管病周围血管病 1.81.8冠心病冠心病冠心病冠心病 1.51.5Am J Hypertens 2000,13:3S-10S Hypertension 1995,25:587-594N Engl J.Med.1996,334:13-18 高血压增加心血管病与肾脏病的危险疾病 8控制血压 保护肾脏 减少有效肾单位增加肾小球增加肾小球内压内压肾硬化与纤维化肾硬化与纤维化肾小球肥厚肾小球肥厚高血压高血压Wang H.Y in APCC控制血压 保护肾脏 减少有效肾单位增加肾小球肾硬化与纤维9高血压伴高血压伴CKD患者增加心血管危险患者增加心血管危险的可能机制的可能机制同型半胱酸增加同型半胱酸增加交感活性增加交感活性增加血浆非对称性二甲基精氨酸（血浆非对称性二甲基精氨酸（asymmetric dimethylarginine,ADMA)浓度增高浓度增高血管钙化的危险性增加血管钙化的危险性增加Updatared from Zoccali C.Kidney Int.2006;70:26-33高血压伴CKD患者增加心血管危险的可能机制同型半胱酸增加Up10概述概述高血压伴高血压伴CKD的处理的处理 内内 容容概述内 容11CKD的处理的处理以抗高血压治疗为主的综合干预以抗高血压治疗为主的综合干预非药物治疗非药物治疗:改善生活方式及专科的营养治疗改善生活方式及专科的营养治疗药物治疗药物治疗:抗高血压药物治疗抗高血压药物治疗 降压目标降压目标 降压药物的选择降压药物的选择 联合治疗联合治疗 多重危险因素的控制（调脂、抗血小板等）多重危险因素的控制（调脂、抗血小板等）CKD的处理以抗高血压治疗为主的综合干预非药物治疗:12CKD患者均应进行抗高血压治疗患者均应进行抗高血压治疗降压降压降低心血管病的危险降低心血管病的危险(不论是否有高血压不论是否有高血压)延缓肾脏病进展延缓肾脏病进展(不论是否有高血压不论是否有高血压)National kidney foundation K/DOQI guideline Am J Kidney Dis.2004:Suppt.1-234CKD患者均应进行抗高血压治疗降压National kidn13降压目标：降压目标：CKD为心血管病的极高危因素，治疗要兼顾延为心血管病的极高危因素，治疗要兼顾延缓肾功能不全进展及降低心血管病危险：缓肾功能不全进展及降低心血管病危险：1、严格控制血压、严格控制血压 (1g/日可更低日可更低)2、降低蛋白尿，使其尽可能恢复正常、降低蛋白尿，使其尽可能恢复正常降压目标：14抗高血压药物的选择与应用选择的原则：选择的原则：遵循指南遵循指南 坚持个化治疗坚持个化治疗首选药物首选药物:（兼有降压、降蛋白尿、延缓（兼有降压、降蛋白尿、延缓GFR降低）降低）抗高血压药物的选择与应用选择的原则：15 各主要权威指南 ESC/ESH(2007)ACEI or ARBESC/ESH(2007)ACEI or ARB ADA(2004)ACEI or ABRADA(2004)ACEI or ABR NKF:DOQI-BP(2004)ACEI or ABRNKF:DOQI-BP(2004)ACEI or ABR KDQI-CKD(2002)ACEI or ABRKDQI-CKD(2002)ACEI or ABR JNC7JNC7（20032003）ACEI or ABRACEI or ABR CHINA(2005)ACEI or ARBCHINA(2005)ACEI or ARB CANADIAN(2002)ACEI or ABRCANADIAN(2002)ACEI or ABR WHO/ISH(1999)ACEIWHO/ISH(1999)ACEI（兼有降压、降蛋白尿、延缓（兼有降压、降蛋白尿、延缓GFR降低）降低）各主要权威指南ESC/ESH(2007)16Save money?限制利尿药的剂量，也限制利尿药的降压作用 限制利尿药的剂量，也限制利尿药的降压作用UKPDS(85 mm Hg,diastolic)低DBP(mmHg)105 484 783 7 83 7RENAAL(140/90 mm Hg)高血压伴CKD患者增加心血管危险的可能机制30-44ml/min/1.HOPE Primary Outcome2005;45:880-886Telmisartan降压强 降压强Reasons for Permanently Stopping Study Medications20%Risk Reduction高血压与主要器官间的关系Time to Primary OutcomeAm J Hypertens 2000,13:3S-10S(Adjusted for SBP)Effect on proteinuriaPrefer tolerability?对对CKD患者治疗患者治疗ACEI vs ARB 孰优孰劣？孰优孰劣？Head-to-head trials Hypertension 0Diabetes type 1 0 type 2 0 with nephropathy 0Post MI(heart failure)OPTIMAAL,VALIANTChronic Heart Failure ELITE IIPervention of disease progression 0High CV risk OntargetHypertension with CKD 0Save money?对CKD患者治疗ACEI vs 17ONTARGET The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial ON MARCH 31,2008 N ENGL J MED,2008;358:1547-1559高血压合并肾损害的处理标准课件18ONTARGETQuestions:1.Is telmisartan“non-inferior”to ramipril?2.Is the combination superior to ramipril?Outcome:Primary:CV death,MI,stroke,CHF hospKey secondary:CV death,MI,stroke(HOPE trial outcome)Design:Single blind run-in(n=29,019)Randomized,double blind,double dummy study conducted in 733 centers in 40 countries(n=25,620)56 months follow-up with 99.8%outcome ascertainmentONTARGETQuestions:19Change in BP(mmHg)RamiprilTelmisartanCombinationSystolic-6.0-6.9-8.4Diastolic-4.6-5.2-6.0Change in BP(mmHg)RamiprilTel20Time to Primary OutcomeONTARGETTime to Primary OutcomeONTARGE21Primary Outcome&HOPE Primary OutcomeRamTelTel vs RamN(%)N(%)RR(95%CI)P(non-inf)N85768542Primary OutcomeCV Death,MI,Stroke,CHF Hosp1412(16.46%)1423(16.66%)1.01(0.94-1.09)0.0038(Adjusted for SBP)1.02(0.95-1.10)0.0055HOPE Primary OutcomeCV Death,MI,Stroke1210(14.11%)1190(13.93%)0.99(0.91-1.07)0.0009(Adjusted for SBP)0.99(0.91-1.07)0.0012Primary Outcome&HOPE Primar22Time to Permanent Discontinuation of Study MedicationONTARGETYears of Follow-upCumulative Hazard Rates0.00.10.20.30.401234TelmisartanRamipril#at Risk Yr 1Yr 2Yr 3Yr 4T85427954738469096478R 85767796716566816254Time to Permanent Discontinuat23Reasons for Permanently Stopping Study MedicationsTelN=8542RamN=8576Tel vs.RamRR PHypotension229(2.7)149(1.7)1.540.0001Syncope19(0.2)15(0.2)1.270.4850Cough93(1.1)360(4.2)0.260.0001Diarrhea19(0.2)12(0.1)1.590.20Angioedema10(0.1)25(0.3)0.400.0115Renal Impairment68(0.8)60(0.7)1.140.46All discontinuation1962(23.0)2099(24.5)0.940.02Reasons for Permanently Stopp24Save money?Prefer tolerability?ARBARBACEIACEITelmisartan is as effective as ramipril,with a slightly better tolerability.Save money?Prefer tolerabili25高血压只有高血压只有30%单药能够达标单药能够达标高血压伴高血压伴CKD时增加额外的降压难度时增加额外的降压难度 （难治性高血压多，目标血压（难治性高血压多，目标血压 130/80mmHg）Number of BP MedicationsUKPDS(85 mm Hg,diastolic)4321MDRD(92 mm Hg,MAP)HOT(80 mm Hg,diastolic)AASK(92 mm Hg,MAP)RENAAL(140/90 mm Hg)IDNT(135/85 mm Hg)联合降压治疗联合降压治疗高血压只有30%单药能够达标高血压伴CKD时增加额外的降压26ON MARCH 31,2008ADA(2004)ACEI or ABRACEI+ARB vs ACEI alone 30%reduction高血压伴CKD患者增加心血管危险的可能机制高17217144 16141 17141 17CKD各期均可用 噻嗪类局限、袢利尿降压差Telmisartan is as effective as ramipril,with a slightly better tolerability.ACEI/HCTZ抗动脉粥样硬化（CHD、IMT）心衰（利尿）ACEI+ARB vs ACEI alone 30%reduction抗高血压药物的选择与应用高血压只有30%单药能够达标高血压伴CKD时增加额外的降压难度 （难治性高血压多，目标血压 130/80mmHg）Effect on proteinuriaTelmisartan2005;45:880-886The ONgoing Telmisartan Alone and in combination联合治疗可获得非常好的血压控制；CHIEF 12000 高危HT CCB+ARB 2011USRDS 2000 Annual Data Report.降压强 降压强利尿剂利尿剂受体阻滞剂受体阻滞剂 ATAT1 1-受体阻滞剂受体阻滞剂 a a受体阻滞剂受体阻滞剂 钙离子拮抗剂钙离子拮抗剂ACEIESH/ESC2007:降压联合治疗方案降压联合治疗方案ON MARCH 31,2008利尿剂受体阻滞剂 AT1-27ACEI与与ARB联合治疗联合治疗(伴伴CKD)BenefitClear role in CHF (CHARM-added,Val-HeFT )Clear role in non-diabetic nephropathy (COOPERATE)Unclear role in diabetic nephropathy (CALM II)Small effect in HT 2007ASH in ChicagoACEI与ARB联合治疗(伴CKD)Benefit28Effect on proteinuriaACEI+ARB vs ACEI alone 30%reduction (95%CI 23-37%)ACEI+ARB vs ARB alone 39%reduction (95%CI 31-48%)(Eight trial reported data on proteinuria,albuminuria,or ACR)Doulton TW,et al.Hypertension.2005;45:880-886Doulton TW,et al.Hypertension.2005;45:880-886Effect on proteinuriaACEI+ARB 29Time to Primary Outcome（ARB与与ACEI联合）联合）ONTARGETTel+RamRam aloneTime to Primary Outcome（ARB与A30Reasons for Permanently Stopping Study MedicationsR+TN=8502RN=8576R+T vs.RRR PHypotension4061492.750.0001Syncope29151.950.032Cough3923601.100.1885Diarrhea39123.280.0001Angioedema18250.730.30Renal Impairment94601.580.0050Total249520991.201.5mg/dl基础血肌酐基础血肌酐 1.5mg/dl肌酐清除率肌酐清除率 60ml/分分/1.73m2肌酐清除率肌酐清除率60ml/分分/1.73m2所有所有 n=15,601HOT研究肾脏病患者亚组数据分析证实非洛地平对肾功能无不良影响Hypertension Unit.J Am Soc Nephrol 2001;12:218-25 1.001.920.981.230.961.011.681.36All discontinuationBaseline Control RatesRASi CCB潜在优势高血压只有30%单药能够达标高血压伴CKD时增加额外的降压难度 （难治性高血压多，目标血压 130/80mmHg）轻度利尿钠 利尿钠（难治高血压，高容量）CKD各期均可用 噻嗪类局限、袢利尿降压差1余学清等,中华肾脏病杂志,2007,23(3)147-151RASiDD（顽固、容量增加时优先）2004;351:1296-1305Primary:CV death,MI,stroke,CHF hospESH/ESC2007:降压联合治疗方案HOT(80 mm Hg,diastolic)7 mmHg p0.TelmisartanACEI/HCTZ联合CCB vs 联合利尿药USRDS 2000 Annual Data Report.(Adjusted for SBP)校正的风险比（所有原因死亡 心血管事件 任何原因住院的）(COOPERATE)Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic HypertensionAll discontinuationAvoiding Ca37Targeted Population for Recruitment into the ACCOMPLISH StudyMen or women age 55 yearsSBP 160 mmHg or currently on antihypertensive therapyEvidence of cardiovascular or renal disease or target organ damageTargeted Population for Recrui38DSMB Oct 17 2007Pre-specified efficacy boundary was crossed with 60%of the expected trial informationExecutive Committee accepted the recommendationLast patient last visit was Jan 24,2008Total of 1176 unique patients with events95.3%of primary events are adjudicatedDSMB Oct 17 2007Pre-specified 39Systolic Blood Pressure Over Timemm HgMonth5731538752064999480442852520104557095377515449804831428625941075PatientsACEI/HCTZN=5733CCB/ACEIN=5713*Mean values are taken at 30 months F/U visit129.3 mmHg130mmHgDifference of 0.7 mmHg p0.05*DBP:71.1DBP:72.8差差1.7mmHgSystolic Blood Pressure Over T40Baseline Control Rates37.237.9ACCOMPLISH:Exceptional Control Rates with Initial Combination TherapyACEI/HCTZN=5733Control rate(%)CCB/ACEIN=571310203040506070809078.581.7P0.001 at 30 months follow-up Control defined as 140/90 mmHgBaseline Control Rates37.237.941Kaplan Meier for Primary EndpointCumulative event rateHR(95%CI):0.80(0.72,0.90)20%Risk ReductionTime to 1st CV morbidity/mortality(days)p=0ACEI/HCTZCCB/ACEI650526.0002INTERIM RESULTS Mar 08Kaplan Meier for Primary Endpo42提提 示示1.联合治疗可获得非常好的血压控制；联合治疗可获得非常好的血压控制；2.初始初始 ACEI/CCB优于优于ACEI/DD的联合治疗，的联合治疗，这对以这对以DD作为降压基础治疗的观点提出挑作为降压基础治疗的观点提出挑战战Initial combinations of Medications diureticsACEI or ARBCCB提 示联合治疗可获得非常好的血压控制；Initial com43利尿治疗的利弊 利尿药抑肾脏钠（镁）重吸收抑肾脏钠（镁）重吸收低镁血症低钠血症低钠血症心排心排低钾血症低钾血症体位性体位性低血压低血压肾血流肾血流PRAGRF糖耐量异常糖耐量异常 高尿酸血症或痛风高尿酸血症或痛风（排泄减少、吸收增加）（排泄减少、吸收增加）其它血容量血容量 限制利尿药的剂量，也限制利尿药的降压作用限制利尿药的剂量，也限制利尿药的降压作用其它机制其它机制利尿治疗的利弊 利尿药抑肾脏钠（镁）重吸收低镁血症低钠血症44高血压伴高血压伴CKD的处理的处理（小（小 结）结）应以降压为主的综合治疗应以降压为主的综合治疗降压需达标（降压需达标（130/80mmHg)首选降压药物：首选降压药物：ACEI或或ARB（靶剂量）（靶剂量）大多数患者需要联合治疗大多数患者需要联合治疗 RASi ARB还需验证（伴还需验证（伴CKD）RASi CCB潜在优势潜在优势 RASiDD（顽固、容量增加时优先）（顽固、容量增加时优先）个体化治疗尤为重要个体化治疗尤为重要高血压伴CKD的处理（小 结）应以降压为主的综合治疗45谢 谢谢谢 谢谢上海瑞金医院上海瑞金医院谢 谢谢 谢上海瑞金医院46