KDIGO关注肾移植受者临床实践指南精解-诱导治课件

KDIGO指南简介（第一部分）肾脏病—改善环球疗效

KDIGO关注肾移植受者临床实践指南

KidneyDisease:ImprovingGlobalOutcomes(KDIGO)

KDIGOclinicalpracticeguidelineforthecareofkidneytransplantrecipients1PPT课件提要KDIGO简介指南简介重要性及权威性如何解读指南指南内容简介诱导治疗研究背景KDIGO推荐依据2PPT课件KDIGO指南KDIGO：KidneyDiseaseImprovingGlobalOutcomesKDIGO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：/3PPT课件权威性KDIGO指南特点科学性系统性实用性易懂性代表性公正性4PPT课件SearchingforEvidence12,327scanned4,000selected937referredTotalAbstracts:12,327RCT:3168Cohort:7,543Cochrane:1,609CloserScrutiny:1,347Immunosuppression:137Monitoring/Infections:670CVD/RiskFactors:244Malignancies/Others2965PPT课件6PPT课件GradeImplicationsPatients CliniciansPolicyLevel1‘Werecommend’推荐级Mostpeopleinyoursituationwouldwanttherecommendedcourseofactionandonlyasmallproportionwouldnot.Mostpatientsshouldreceivetherecommendedcourseofaction.Therecommendationcanbeadoptedasapolicyinmostsituations.Level2‘Wesuggest’建议级Themajorityofpeopleinyoursituationwouldwanttherecommendedcourseofaction,butmanywouldnot.Differentchoiceswillbeappropriatefordifferentpatients.Eachpatientneedshelptoarriveatamanagementdecisionconsistentwithherorhisvaluesandpreferences.Therecommendationislikelytorequiredebateandinvolvementofstakeholdersbeforepolicycanbedetermined.指南分级的意义7PPT课件RatingGuidelineRecommendations（9级）

Withineachrecommendation,thestrengthofrecommendationisindicatedasLevel1,Level2,orNotGraded,andthe

qualityofthesupportingevidenceisshownasA,B,C,orD.

Grade*

WordingLevel1

‘Werecommend’Level2

‘Wesuggest’NotGradedA HighB ModerateC LowD Very

low*Theadditionalcategory‘NotGraded’wasused,typically,toprovideguidancebasedoncommonsenseorwherethetopicdoesnotallowadequateapplicationofevidence.Themostcommonexamplesincluderecommendationsregardingmonitoringintervals,counseling,andreferraltootherclinicalspecialists.Theungradedrecommendationsaregenerallywrittenassimpledeclarativestatements,butarenotmeanttobeinterpretedasbeingstrongerrecommendationsthanLevel1or2recommendations.Gradefor

qualityOf

evidenceQualityofevidence8PPT课件《KDIGO肾移植指南》章节一览表：SectionI:ImmunosuppressionChapter1:InductionTherapyChapter2:InitialMaintenanceImmunosuppressiveMedicationsChapter3:Long-TermMaintenanceImmunosuppressiveMedicationsChapter4:StrategiestoReduceDrugCostsChapter5:MonitoringImmunosuppressiveMedicationsChapter6:TreatmentofAcuteRejectionChapter7:TreatmentofChronicAllograftInjurySectionII:GraftMonitoringandInfectionsChapter8:MonitoringKidneyAllograftFunctionChapter9:KidneyAllograftBiopsyChapter10:RecurrentKidneyDiseaseChapter11:Preventing,Detecting,andTreatingNonadherenceChapter12:VaccinationChapter13:ViralDiseasesChapter14:OtherInfectionsSectionIII:CardiovascularDiseaseChapter15:DiabetesMellitusChapter16:Hypertension,Dyslipidemias,TobaccoUse,andObesityChapter17:CardiovascularDiseaseManagementSectionIV:MalignancyChapter18:CanceroftheSkinandLipChapter19:Non–SkinMalignanciesChapter20:ManagingCancerwithReductionofImmunosuppressiveMedicationSectionV:OtherComplicationsChapter21:TransplantBoneDiseaseChapter22:HematologicalComplicationsChapter23:HyperuricemiaandGoutChapter24:GrowthandDevelopmentChapter25:SexualFunctionandFertilityChapter26:LifestyleChapter27:MentalHealth9PPT课件Chapter1:

InductionTherapy1.1:Werecommendstartingacombinationofimmunosuppressive medicationsbefore,oratthetimeof,kidneytransplantation.(1A)1.2:WerecommendincludinginductiontherapywithabiologicagentaspartoftheinitialimmunosuppressiveregimeninKTRs.(1A) 1.2.1:WerecommendthatanIL2-RAbethefirstlineinductiontherapy.(1B) 1.2.2:Wesuggestusingalymphocyte-depletingagent,ratherthananIL2-RA,forKTRsathighimmunologicrisk.(2B)IL2-RA,interleukin2receptorantagonist;KTRs,kidneytransplantrecipients.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（KidneyTransplantRecipient,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Background研究背景12PPT课件诱导治疗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,OKT3IL-2RA：嵌合型单抗，人源化单抗13PPT课件抗CD25单抗vs清除性抗体抗CD25单抗OKT3/ATG/ALG

注册适应症

预防急性排斥

治疗急性排斥延迟首次排斥发生

作用机制仅作用于激活的T淋巴细胞，不影响其他T细胞杀灭所有T细胞

已证实疗效可将急排发生率降低近40%提高患者及器官存活率

提高治疗急性排斥的成功率；延迟首次急性排斥的发生14PPT课件抗CD25单抗vs清除性抗体抗CD25单抗OKT3/ATG/ALG

安全性

不增加机会感染不增加淋巴细胞增生性疾病没有显著不良事件

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反应，包括细胞因子释放综合症

其他临床优势可延迟CNI的使用，降低给药剂量；实现激素早期撤除；15PPT课件RationaleKDIGO推荐理由16PPT课件推荐理由（一）高质量证据证实：不同的肾移植受者接受不同的免疫抑制方案联合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Meta分析：IL-2RA显著降低急排反应发生Transplantation2004;77:166–17618PPT课件Meta分析：IL-2RA不增加CMV感染发生Transplantation2004;77:166–17619PPT课件IL-2RAvs清除性抗体：显著降低CMV感染

及其他不良反应发生Transplantation2004;77:166–17620PPT课件IL-2RA诱导：移植物存活率最高Transplantation2006;81:1227–123321PPT课件多抗诱导：非霍奇金淋巴瘤累计发生率升高Transplantation2006;81:1227–123322PPT课件药物经济学研究结果IL-2RA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患者成本（12个月）患者成本（20年）LYS（20年）QALY（20年）非诱导治疗$89188$3456497.053.86IL-2RA诱导治疗$85227$2663477.265.28LYS：lifeyearsgainedQALY：qualityadjustedlifeyears

NephrolDialTransplant2009;24:2258–2269.23PPT课件药物经济学研究结果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）：14803/LYS；$25928/QALY治疗更有效：延长0.35LYS（4.3月），0.2QALYLYS：lifey