ACEI和ARB类药物在糖尿病肾病中的应用课件.ppt

1、Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time ACEI和和ARB类药物类药物在糖尿病肾病中的应用在糖尿病肾病中的应用Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 肾脏与血压肾脏与血压肾脏对循环容量的调节肾脏对循环容量的调节 1 1，利钠肽，利钠肽 排钠利尿排钠

2、利尿 2 2，花生四烯酸（，花生四烯酸（AAAA）代谢产物（）代谢产物（前列腺素前列腺素E E2 2、前列环素、前列环素）抑制钠的重吸收，排钠利尿抑制钠的重吸收，排钠利尿 3,3,肾素肾素-血管紧张素血管紧张素-醛固酮系统醛固酮系统 醛固酮能促进钠水醛固酮能促进钠水重吸收重吸收 4 4，抗利尿激素，抗利尿激素促进钠水重吸收促进钠水重吸收 5 5，肾脏交感神经活性，肾脏交感神经活性促进钠水重吸收促进钠水重吸收钠水潴留钠水潴留Our greatest weakness lies in giving up.The most certain way to succeed is always to tr

3、y just one more time 肾脏对外周血管阻力的调节肾脏对外周血管阻力的调节(收缩和舒张血管物质收缩和舒张血管物质)肾素肾素-血管紧张素系统血管紧张素系统 内皮素内皮素 交感神经释放的介质交感神经释放的介质 花生四烯酸（花生四烯酸（AAAA）代谢产物）代谢产物 激肽释放酶激肽释放酶-激肽系统激肽系统 内皮源血管舒张因子内皮源血管舒张因子 一氧化氮一氧化氮(NO)(NO)Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time

4、 肾素肾素-血管紧张素系统（血管紧张素系统（RASRAS）肾素（肾素（reninrenin）血管紧张素原（血管紧张素原（angiotensinogenangiotensinogen）血管紧张素血管紧张素(angiotensin)(angiotensin)血管紧张素转化酶血管紧张素转化酶 （angiotensin-converting enzymeangiotensin-converting enzyme，ACEACE）血管紧张素血管紧张素（angiotensin angiotensin）血管紧张素受体（血管紧张素受体（angiotensin receptorsangiotensin recep

5、tors）Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 血管紧张素血管紧张素的生物学作用的生物学作用 全身血流动力学改变全身血流动力学改变 促进细胞增生和肥大促进细胞增生和肥大 促进活性氧（促进活性氧（ROS）产生）产生 促进转化生长因子促进转化生长因子-（TGF-）产生）产生 促进炎性介质的产生促进炎性介质的产生 粘附分子、内皮素等粘附分子、内皮素等 刺激化学趋化因子的产生刺激化学趋化因子的产生 MCP-1 促进凝血、抑制纤

6、溶反应促进凝血、抑制纤溶反应 其他其他 促进细胞凋亡，影响胰岛素和脂质代谢促进细胞凋亡，影响胰岛素和脂质代谢Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time RAS在肾脏疾病中的作用在肾脏疾病中的作用 RAS包括循环和局部两部分，过度兴包括循环和局部两部分，过度兴奋参与许多肾脏疾病，其中局部奋参与许多肾脏疾病，其中局部RAS作用作用日益受到重视日益受到重视 局部主要存在于局部主要存在于 近端肾小管近端肾小管 系膜细胞系膜细胞 足细

7、胞足细胞 间质细胞间质细胞Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 高血压高血压 肾脏内血流动力学异常肾脏内血流动力学异常 蛋白尿蛋白尿 肾小球硬化和肾间质纤维化肾小球硬化和肾间质纤维化RAS在肾脏疾病中的作用在肾脏疾病中的作用Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one m

8、ore time 阻断阻断RAS的手段的手段 血管紧张素转换酶抑制剂（血管紧张素转换酶抑制剂（ACEI）血管紧张素受体血管紧张素受体拮抗剂拮抗剂 肾素受体阻断及糜蛋白酶阻断肾素受体阻断及糜蛋白酶阻断Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 心肾疾病的相互影响心肾疾病的相互影响 心脏是为循环系统提供动力的核心心脏是为循环系统提供动力的核心 肾脏在维持内环境稳定方面发挥重要作用，肾脏在维持内环境稳定方面发挥重要作用，通过维持血

9、容量，来维持血液动力学稳定通过维持血容量，来维持血液动力学稳定 在生理上心肾相互依存在生理上心肾相互依存 在病理状态下心肾相互影响在病理状态下心肾相互影响Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 肾脏病对心脏的影响肾脏病对心脏的影响 慢性肾脏病慢性肾脏病(CKD)在世界范围内是一个严重在世界范围内是一个严重的健康问题，美国的健康问题，美国CKD的发病率为的发病率为11%，中国中国CKD的发病率的发病率10%美国的统计数据显

10、示需要透析或肾移植的美国的统计数据显示需要透析或肾移植的病人病人1998年为年为32万，预计万，预计2010年年65万万K/DOQIOur greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 终末期肾病患者合并心血管疾病后，年死终末期肾病患者合并心血管疾病后，年死亡率是普通人群的亡率是普通人群的10-30倍倍 接受肾移植患者心血管病的死亡率占总死接受肾移植患者心血管病的死亡率占总死亡率的亡率的30%-50%叶平、程庆砾Clinical Ca

11、rdiorenal Intersection DiseaseOur greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 普通人群和普通人群和CKD患者中心血管疾病的发生情况患者中心血管疾病的发生情况叶平、程庆砾Clinical Cardiorenal Intersection DiseaseOur greatest weakness lies in giving up.The most certain way to succeed is a

12、lways to try just one more time 心脏病对肾脏的影响心脏病对肾脏的影响 心力衰竭心力衰竭外周淤血，静脉压升高外周淤血，静脉压升高肾脏肾脏淤血淤血肾功能不全肾功能不全 心脏介入治疗的普及心脏介入治疗的普及造影剂肾病（造影剂肾病（CIN）的发生率升高的发生率升高Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 13%非糖尿病患者和非糖尿病患者和20%糖尿病患者在心糖尿病患者在心脏介入治疗后血肌酐较基础值升

13、高脏介入治疗后血肌酐较基础值升高25%以以上或绝对值超过上或绝对值超过44.2mol/L（0.5mg/dl）引起造影剂肾病引起造影剂肾病 约约0.5%-2%发展到透析发展到透析 住院死亡率住院死亡率36%2年存活率年存活率19%叶平、程庆砾Clinical Cardiorenal Intersection DiseaseOur greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time CKD患者心血管疾病的危险因素患者心血管疾病的危险因素Our

14、greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 慢性肾脏疾病的定义慢性肾脏疾病的定义 1、肾损害3个月，肾损害指肾脏结构或功能异常，伴/不伴GFR降低，表现为下列之一：病理异常；或 有肾损害指标，包括血或尿成分异常，或影像学检查异常 2、GFR60ml/min/1.73m个月，有或无肾损害K/DOQIOur greatest weakness lies in giving up.The most certain way to succe

15、ed is always to try just one more time 慢性肾脏疾病的分期慢性肾脏疾病的分期简化的简化的MDRD方程方程 GFR=186(Scr)-1.154年龄-0.203(0.742女性)(1.210非裔)K/DOQIOur greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 我国对慢性肾功能不全的分期我国对慢性肾功能不全的分期Our greatest weakness lies in giving up.The

16、most certain way to succeed is always to try just one more time 肾衰竭的定义肾衰竭的定义 肾衰竭是指肾衰竭是指GFR15ml/min/1.73m2,此时常伴有尿毒症的症状与体征，或需开此时常伴有尿毒症的症状与体征，或需开始给予肾脏替代治疗（透析或移植）来治始给予肾脏替代治疗（透析或移植）来治疗疗GFR降低的并发症，否则患病率、病死降低的并发症，否则患病率、病死率将升高。率将升高。有些病人由于出现尿毒症症状，在有些病人由于出现尿毒症症状，在GFR15ml/min/1.73m2时就需要透析或肾时就需要透析或肾移植治疗。移植治疗。Our

17、 greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 糖尿病肾病糖尿病肾病MogensenMogensen分期分期Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain

18、way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giv

19、ing up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 指南指南 1 1：

20、糖尿病肾病的筛查和诊断：糖尿病肾病的筛查和诊断 患有糖尿病的患有糖尿病的CKDCKD病人可以表现为糖尿病肾病，病人可以表现为糖尿病肾病，也可以不表现为糖尿病肾病。也可以不表现为糖尿病肾病。缺乏明确诊断的情况下，糖尿病和肾病病人缺乏明确诊断的情况下，糖尿病和肾病病人的评估应该包括针对以下病因的研究探讨。的评估应该包括针对以下病因的研究探讨。2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUPPL 2,FEBRUARY 2007Our greatest

21、weakness lies in giving up.The most certain way to succeed is always to try just one more time 1.1 1.1 糖尿病病人应该每年进行糖尿病肾病的筛查。糖尿病病人应该每年进行糖尿病肾病的筛查。最初的筛查范围包括：最初的筛查范围包括：型糖尿病诊断后型糖尿病诊断后5 5年的病人或年的病人或 型糖尿病诊断成立的病人型糖尿病诊断成立的病人 1.1.1 1.1.1 筛查应该包括：筛查应该包括：定点尿样定点尿样尿蛋白尿蛋白/肌酐比率（肌酐比率（ACRACR）的检测的检测 ACR=ACR=尿蛋白尿蛋白(mg(mgL

22、)L)尿肌酐尿肌酐(g(gL)L)血清肌酐的检测和血清肌酐的检测和GFRGFR的计算的计算2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUPPL 2,FEBRUARY 2007Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in

23、giving up.The most certain way to succeed is always to try just one more time 微量白蛋白尿微量白蛋白尿(MAU)(MAU)和肾小球滤过率和肾小球滤过率(GFR)(GFR)的的评估是糖尿病肾病筛查的标准检查。评估是糖尿病肾病筛查的标准检查。Microalbuminuria(MAU)Glomerular Filtration Rate(GFR)2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49

24、,NO 2,SUPPL 2,FEBRUARY 2007Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 1.2 ACR 1.2 ACR（尿蛋白（尿蛋白/肌酐比率）升高者应该肌酐比率）升高者应该排除尿路感染，并在以后的排除尿路感染，并在以后的3-63-6个月收集另外个月收集另外2 2次次首段尿首段尿(first-void specimens(first-void specimens)进行检测证实。进行检测证实。ACR 30-300m

25、g/gACR 30-300mg/g称为微量蛋白尿。称为微量蛋白尿。ACR 300mg/gACR 300mg/g称为大量蛋白尿。称为大量蛋白尿。3 3次中的次中的2 2次样本属于微量蛋白尿或大量蛋次样本属于微量蛋白尿或大量蛋白尿范围可确认分级。白尿范围可确认分级。2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUPPL 2,FEBRUARY 2007Our greatest weakness lies in giving up.The most cer

26、tain way to succeed is always to try just one more time 1.3 1.3 如果出现以下情况，大多数糖尿病病人如果出现以下情况，大多数糖尿病病人是因为糖尿病导致慢性肾脏病：是因为糖尿病导致慢性肾脏病：出现大量蛋白尿或出现大量蛋白尿或 出现微量蛋白尿同时出现微量蛋白尿同时 存在糖尿病视网膜病变存在糖尿病视网膜病变 型糖尿病至少型糖尿病至少1010年年2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUP

27、PL 2,FEBRUARY 2007Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 1.4 1.4 出现任何下列情况，应该考虑出现任何下列情况，应该考虑CKDCKD的其他的其他病因：病因：无糖尿病视网膜病变无糖尿病视网膜病变 GFRGFR低或低或GFRGFR迅速降低迅速降低 蛋白尿迅速增多或肾病综合征蛋白尿迅速增多或肾病综合征 难以控制的高血压难以控制的高血压 活动性尿沉淀活动性尿沉淀 其他系统性疾病的征兆或症状或其他系统性疾病

28、的征兆或症状或 开始开始ACEIACEI或或ARBARB治疗后，治疗后，2-32-3个月内个月内GFRGFR减少减少30%30%2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUPPL 2,FEBRUARY 2007Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 因为尿白蛋白排泄的变异

29、性，通过收集3-6个月内至少2次样本的检测才能确定(最好是晨起首次尿)。24小时内有过运动、感染、发热、小时内有过运动、感染、发热、充血性心衰、显著高糖、妊娠、显著的高血压、尿路感染、和血尿均充血性心衰、显著高糖、妊娠、显著的高血压、尿路感染、和血尿均可导致尿蛋白超过基线值。可导致尿蛋白超过基线值。2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUPPL 2,FEBRUARY 2007Our greatest weakness lies in giv

30、ing up.The most certain way to succeed is always to try just one more time 指南：糖尿病和慢性肾脏病指南：糖尿病和慢性肾脏病高血压的处理高血压的处理大部分糖尿病和慢性肾脏病的病人伴有高血大部分糖尿病和慢性肾脏病的病人伴有高血压。高血压的治疗能减缓慢性肾脏病的进程。压。高血压的治疗能减缓慢性肾脏病的进程。2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUPPL 2,FEBRUAR

31、Y 2007Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is alw

32、ays to try just one more time 3.1 3.1 糖尿病和慢性肾脏病糖尿病和慢性肾脏病1-41-4期的高血压病人期的高血压病人应该用应该用ACEIACEI或或ARBARB治疗，通常联合使用利尿剂。治疗，通常联合使用利尿剂。2007 KDOQI CPG and CPR for Diabetes and CKDfrom American Journal of Kidney Diseases VOL 49,NO 2,SUPPL 2,FEBRUARY 2007Our greatest weakness lies in giving up.The most certain wa

33、y to succeed is always to try just one more time 3.2 3.2 糖尿病和慢性肾脏病糖尿病和慢性肾脏病1-41-4期病人的目标期病人的目标血压应该是血压应该是25.0mg/mmol25.0mg/mmol（220mg/g220mg/g）（男、女）（男、女）Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 应每年检测血清肌酐浓度。应每年检测血清肌酐浓度。确诊糖尿病肾病前必须除外其它肾脏疾

34、病，确诊糖尿病肾病前必须除外其它肾脏疾病，必要时需做肾穿刺病理检查。必要时需做肾穿刺病理检查。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 治疗治疗 首选血管紧张素转换酶抑制剂（首选血管紧张素转换酶抑制剂（ACEIACEI）或）或血管紧张素血管紧张素IIII受体阻断剂（受体阻断剂（ARBARB），即使血），即使血压正常，亦应该使用。压正常，亦应该使用。在开始使用这些药在开始使用这些药物的前物的前1-21-2周内检测血清肌酐和血

35、钾浓度。周内检测血清肌酐和血钾浓度。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 应积极治疗高血压，血压目标值应维持在应积极治疗高血压，血压目标值应维持在130/80mmHg130/80mmHg以下。大量蛋白尿患者血压应以下。大量蛋白尿患者血压应控制在控制在125/75mmHg125/75mmHg以下。以下。通常需要多种降压药联合应用。通常需要多种降压药联合应用。Our greatest weakness lies in gi

36、ving up.The most certain way to succeed is always to try just one more time 积极控制血糖和其他心血管疾病的危险因积极控制血糖和其他心血管疾病的危险因素，特别是血脂异常等。素，特别是血脂异常等。应考虑存在非糖尿病性肾脏疾病的可能性，应考虑存在非糖尿病性肾脏疾病的可能性，特别是在无糖尿病视网膜病变时出现持续特别是在无糖尿病视网膜病变时出现持续性血尿，或者只有轻微的蛋白尿，而血肌性血尿，或者只有轻微的蛋白尿，而血肌酐浓度却相对较高。酐浓度却相对较高。Our greatest weakness lies in giving u

37、p.The most certain way to succeed is always to try just one more time 阻断肾素阻断肾素-血管紧张素系统血管紧张素系统在糖尿病肾病中的应用在糖尿病肾病中的应用 PRIME研究（研究（PRogram for Irbesartan Mortality and Morbidity Evaluations)RENAAL研究（研究（reduction of endpoints in NIDDM with the angiotensin antogonist losartan）Our greatest weakness lies in g

38、iving up.The most certain way to succeed is always to try just one more time RENAALRENAAL研究研究 是是ARBARB治疗治疗2 2型糖尿病肾病的大型临床试验，型糖尿病肾病的大型临床试验，是唯一有亚洲人群参加的此类试验（亚裔是唯一有亚洲人群参加的此类试验（亚裔占占17%17%）。）。2525个国家个国家250250个中心的个中心的15131513例例2 2型糖尿病肾型糖尿病肾病患者，随访病患者，随访4 4年。年。Our greatest weakness lies in giving up.The most

39、certain way to succeed is always to try just one more time 结果结果：氯沙坦：氯沙坦治疗后，治疗后，(A)(A)联联合终点的风险下合终点的风险下降降16%16%，(B)(B)血肌血肌酐倍增的风险下酐倍增的风险下降降25%25%，(C)(C)终末终末期肾病的风险下期肾病的风险下降降28%28%。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 结果结果：与对照：与对照组相比蛋

40、白尿下组相比蛋白尿下降降35%35%，Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time PRIMEPRIME研究研究 是是验证验证IrbesartanIrbesartan对对2 2型糖尿病肾病治疗作型糖尿病肾病治疗作用的重要大型临床试验。用的重要大型临床试验。Our greatest weakness lies in giving up.The most certain way to succeed is always to tr

41、y just one more time 第一部分（第一部分（IRMA2IRMA2）是对）是对590590例伴高血压的例伴高血压的早期早期2 2型糖尿病肾病，对比型糖尿病肾病，对比2 2年后糖尿病肾年后糖尿病肾病的发生率。病的发生率。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time IrbesartanIrbesartan 150mg/d 150mg/d组、组、300mg/d300mg/d组和组和安慰剂组的尿安慰剂组的尿白蛋白排泄

42、率白蛋白排泄率（UAEUAE）变化）变化Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 第二部分（第二部分（IDNTIDNT）即应用）即应用IrbesartanIrbesartan后对后对肾功能的影响，肾功能的影响，17151715例有高血压、明显蛋例有高血压、明显蛋白尿的白尿的2 2型糖尿病患者随机双盲分为型糖尿病患者随机双盲分为3 3组，组，与氨氯地平和其他传统降压药对照。平均与氨氯地平和其他传统降压药对照。平均随访随访2.

43、62.6年。年。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 显著降低到达主要终点的危险性显著降低到达主要终点的危险性20%20%Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 显著降低到达血肌酐翻倍的危险性显著降低到达血肌酐翻倍的危险性33%33%Our gr

44、eatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 显著降低到达显著降低到达ESRDESRD的危险性的危险性23%23%Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 提示：提示：IrbesartanIrbesartan风险低风险低明显延缓主要终点事件的发生明显延缓主要终点事件的

45、发生是早期控制蛋白尿的重要手段是早期控制蛋白尿的重要手段甚至部分病人能完全逆转甚至部分病人能完全逆转Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 厄贝沙坦是糖尿病伴高血压或蛋白尿厄贝沙坦是糖尿病伴高血压或蛋白尿治疗的理想选择治疗的理想选择Our greatest weakness lies in giving up.The most certain way to succeed is always to try just on

46、e more time 厄贝沙坦对厄贝沙坦对AT1的阻断作用比缬沙的阻断作用比缬沙坦和氯沙坦强，时间也更持久坦和氯沙坦强，时间也更持久Burnier M.Circulation.2001;103;904-912Kassler-Taub K,et al.Am J Hypertens.1998;11(4 Pt 1):445-453 Mancia G,et al.Blood Pressure Monitoring.2002;7:135-142Our greatest weakness lies in giving up.The most certain way to succeed is alway

47、s to try just one more time 总总 结结 肾脏是调节血压的重要器官肾脏是调节血压的重要器官 肾素肾素-血管紧张素系统（血管紧张素系统（RASRAS）在肾脏疾病）在肾脏疾病中扮演重要角色中扮演重要角色 心肾疾病能相互影响心肾疾病能相互影响 糖尿病肾病危害很大需要早期防治糖尿病肾病危害很大需要早期防治 阻断肾素阻断肾素-血管紧张素系统（血管紧张素系统（RASRAS）至关重）至关重要要 厄贝沙坦是医生理想的选择厄贝沙坦是医生理想的选择Our greatest weakness lies in giving up.The most certain way to succeed

48、 is always to try just one more time 谢谢谢谢Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time