KDIGO关注肾移植受者临床实践指南精解-诱导治课件.ppt

1、KDIGO指南简介（第一部分）肾脏病肾脏病改善环球疗效改善环球疗效 KDIGOKDIGO关注肾移植受者临床实践指南关注肾移植受者临床实践指南Kidney Disease: Improving Global Outcomes (KDIGO)KDIGO clinical practice guideline for the care of kidney transplant recipients1PPT课件1.1.KDIGOKDIGO简介简介指南简介指南简介重要性及权威性重要性及权威性如何解读指南如何解读指南指南内容简介指南内容简介2.2.诱导治疗诱导治疗研究背景研究背景KDIGOKDIGO推荐依

2、据推荐依据2PPT课件KDIGOKDIGO指南KDIGO：Kidney Disease Improving Global OutcomesKDIGO国际委员会成立于2003年，一个独立的、非赢利的国际组织，由拥有12年指南制定经验的美国国立肾脏基金会管理网址：http:/www.kdigo.org/3PPT课件权威性权威性KDIGOKDIGO指南特点1.1.科学性科学性2.2.系统性系统性3.3.实用性实用性4.4.易懂性易懂性5.5.代表性代表性6.6.公正性公正性4PPT课件Searching for Evidence12,327 scanned 12,327 scanned 4,000

3、selected 4,000 selected 937 937 referredreferredTotal Abstracts: 12,327RCT:3168Cohort:7,543Cochrane: 1,609 Closer Scrutiny: 1,347Immunosuppression: 137Monitoring/Infections: 670CVD / Risk Factors:244Malignancies/Others 2965PPT课件6PPT课件GradeImplicationsPatients Clinicians PolicyLevel 1We recommend推荐级推

4、荐级Most people in your situationwould want the recommendedcourse of action and only asmall proportion would not.Most patients should r e c e i v e t h e recommended course of action.The recommendation can be adopted as a policy in most situations.Level 2We suggest建议级建议级The majority of people in yours

5、ituation would want the recommended course of action, but many would not.Different choices will be appropriate for different patients. Each patientneeds help to arrive at a management decision consistent with her or his values and preferences.The recommendation is likely to require debate and involv

6、ement of stakeholders before policy can be determined.指南分级的意义指南分级的意义7PPT课件Rating Guideline Recommendations（9级）Within each recommendation, the strength of recommendation is indicated as Level 1, Level 2, or Not Graded, and thequality of the supporting evidence is shown as A, B, C, or D.GradeGrade* *

7、WordingWordingL e v e l 1L e v e l 1 W e W e recommendrecommendLevel 2 Level 2 We suggestWe suggestNot GradedNot GradedA A HighHighB B ModerateModerateC C LowLowD D VeryVery lowlow*The additional category Not Graded was used, typically, to provide guidance based on common sense orwhere the topic doe

8、s not allow adequate application of evidence. The most common examples includerecommendations regarding monitoring intervals, counseling, and referral to other clinical specialists. Theungraded recommendations are generally written as simple declarative statements, but are not meant tobe interpreted

9、 as being stronger recommendations than Level 1 or 2 recommendations.Grade for quality Of evidenceQuality of evidence8PPT课件KDIGO肾移植指南肾移植指南章节一览表：章节一览表：Section I: Section I: ImmunosuppressionImmunosuppressionChapter 1: Induction TherapyChapter 2: Initial Maintenance Immunosuppressive MedicationsChapte

10、r 3: Long-Term Maintenance Immunosuppressive MedicationsChapter 4: Strategies to Reduce Drug CostsChapter 5: Monitoring Immunosuppressive MedicationsChapter 6: Treatment of Acute RejectionChapter 7: Treatment of Chronic Allograft InjurySection II: Section II: Graft Monitoring and Graft Monitoring an

11、d InfectionsInfectionsChapter 8: Monitoring Kidney Allograft FunctionChapter 9: Kidney Allograft BiopsyChapter 10: Recurrent Kidney DiseaseChapter 11: Preventing, Detecting, and Treating NonadherenceChapter 12: VaccinationChapter 13: Viral DiseasesChapter 14: Other InfectionsSection III: Section III

12、: Cardiovascular DiseaseCardiovascular DiseaseChapter 15: Diabetes MellitusChapter 16: Hypertension, Dyslipidemias, Tobacco Use, and ObesityChapter 17: Cardiovascular Disease ManagementSection IV: Section IV: MalignancyMalignancyChapter 18: Cancer of the Skin and LipChapter 19: NonSkin MalignanciesC

13、hapter 20: Managing Cancer with Reduction of Immunosuppressive MedicationSection V: Section V: Other ComplicationsOther ComplicationsChapter 21: Transplant Bone DiseaseChapter 22: Hematological ComplicationsChapter 23: Hyperuricemia and GoutChapter 24: Growth and DevelopmentChapter 25: Sexual Functi

14、on and FertilityChapter 26: LifestyleChapter 27: Mental Health9PPT课件Chapter 1: Induction Therapy1.1: We recommend starting a combination of immunosuppressive1.1: We recommend starting a combination of immunosuppressive medications before, or at the time of, kidney medications before, or at the time

15、of, kidney transplantation. transplantation. (1A) (1A)1.2: We recommend including induction therapy with a biologic 1.2: We recommend including induction therapy with a biologic agent as part of the initial immunosuppressive agent as part of the initial immunosuppressive regimen in regimen in KTRs.

16、KTRs. (1A)(1A)1.2.1: We recommend that an IL2-RA be the 1.2.1: We recommend that an IL2-RA be the first line first line inductioninduction therapy. therapy. (1B) (1B)1.2.2: We suggest using a lymphocyte-depleting agent, 1.2.2: We suggest using a lymphocyte-depleting agent, rather rather than an IL2-

17、RA, for KTRs at high immunologic than an IL2-RA, for KTRs at high immunologic risk. (2B)risk. (2B)IL2-RA, interleukin 2 receptor antagonist; KTRs, kidney transplant recipients.IL2-RA, interleukin 2 receptor antagonist; KTRs, kidney transplant recipients.10PPT课件Chapter1：诱导治疗1.1 推荐在肾移植术前或术中即开始联合应用免疫抑制

18、药物（1A）1.2 推荐将使用生物制剂进行诱导治疗纳入到肾移植受者（Kidney Transplant Recipient, KTR）初始的免疫抑制方案中（1A）1.2.1 推荐白介素2受体拮抗剂（IL2Ra）作为诱导治疗的一线用药（1B）1.2.2 对于有高排斥风险的肾移植受者，建议使用抗淋巴细胞制剂而不是白介素2受体拮抗剂（2B）11PPT课件12PPT课件所有肾移植患者均需接受免疫抑制药物治疗，以预防排斥反应的发生诱导治疗可以改善免疫抑制疗效 减少急性排斥反应的发生 减少其它免疫抑制药物用量，如CNIs，激素免疫诱导药物 清除性抗体：ATG, ALG, OKT3 IL-2RA：嵌合型单抗

19、，人源化单抗13PPT课件抗抗CD25CD25单抗单抗 OKT3/ATG/ALG OKT3/ATG/ALG 注册适应症注册适应症 预防急性排斥预防急性排斥 治疗急性排斥治疗急性排斥 延迟首次排斥发生延迟首次排斥发生 作用机制作用机制 仅作用于激活的仅作用于激活的T T淋巴细胞，不影淋巴细胞，不影 响其他响其他T T细胞细胞 杀灭所有杀灭所有T T细胞细胞 已证实疗效已证实疗效 可将急排发生率降低近可将急排发生率降低近40%40% 提高患者及器官存活率提高患者及器官存活率 提高治疗急性排斥的成功率；提高治疗急性排斥的成功率； 延迟首次急性排斥的发生延迟首次急性排斥的发生14PPT课件 抗抗CD2

20、5CD25单抗单抗 OKT3/ATG/ALG OKT3/ATG/ALG 安全性安全性 不增加机会感染不增加机会感染 不增加淋巴细胞增生性疾病不增加淋巴细胞增生性疾病 没有显著不良事件没有显著不良事件 导致所有与过度免疫相关的副作用，包导致所有与过度免疫相关的副作用，包 括机会感染和淋巴细胞增生性疾病首剂括机会感染和淋巴细胞增生性疾病首剂 反应，包括细胞因子释放综合症反应，包括细胞因子释放综合症 其他临其他临 床优势床优势可延迟可延迟CNICNI的使用，降低给药剂量；的使用，降低给药剂量；实现激素早期撤除；实现激素早期撤除；15PPT课件16PPT课件高质量证据证实：不同的肾移植受者接受不同的免

21、疫抑制方案联合IL-2RA诱导治疗对比不联合IL-2RA诱导治疗（或安慰剂），带给患者的受益远远大于伤害；药物经济学研究显示：IL-2RA对比安慰剂，降低患者治疗费用，改善移植物生存；17PPT课件Transplantation 2004; 77: 16617618PPT课件Transplantation 2004; 77: 16617619PPT课件Transplantation 2004; 77: 16617620PPT课件Transplantation 2006;81: 1227123321PPT课件Transplantation 2006;81: 1227123322PPT课件IL-2

22、RA对比安慰剂/非诱导治疗治疗成本更低 移植第1年节省治疗费用$3633，20年节省$79302治疗更有效 延长0.21生命年（2.5月），1.42质量调整生命年方案方案患者成本患者成本（1212个月）个月）患者成本患者成本（2020年）年） LYS LYS（2020年）年）QALYQALY（2020年）年）非诱导治疗非诱导治疗$89 188$89 188$345 649$345 6497.057.053.863.86IL-2RAIL-2RA诱导治疗诱导治疗$85 227$85 227$266 347$266 3477.267.265.285.28LYS：life years gained Q

23、ALY：quality adjusted life years Nephrol Dial Transplant 2009; 24: 22582269.23PPT课件IL-2RA对比多抗免疫诱导治疗肾移植增量成本$5144；ICER(增量成本效益比）：14 803/LYS；$25 928/QALY治疗更有效：延长0.35LYS（4.3月），0.2QALYLYS：life years gainedQALY：quality adjusted life years 方案方案患者成本患者成本（1212个月）个月）患者成本患者成本（2020年）年）LYSLYS（2020年）年）QALYQALY（2020年

24、）年）IL-2RAIL-2RA诱导治疗诱导治疗$85 227$85 227$266 347$266 3477.267.265.285.28多抗诱导治疗多抗诱导治疗$88 860$88 860$261 203$261 2036.916.915.085.08Nephrol Dial Transplant 2009; 24: 22582269.24PPT课件中等质量证据证实：清除性抗体对比IL-2RA，减少急排的发生，但增加感染及恶性肿瘤的风险；清除性抗体对比IL-2RA免疫诱导肾移植，减少急排发生率，但不能延长移植物存活时间；清除性抗体免疫诱导肾移植，增加严重不良反应的发生率；25PPT课件*p0.05N Engl JMed 2006; 355: 1967197726PPT课件*p0.05N Engl JMed 2006; 355: 1967197727PPT课件*p0.0528PPT课件Nephrol Dial Transplant.2008; 23: 2024203229PPT课件Thanks！30PPT课件