狼疮性肾炎PPT课件.ppt

狼疮性肾炎,1,免疫学检查,病因与发病机制,狼疮性肾炎,诊断和治疗,2,Factorsassociatedwithdevelopmentofsystemiclupuserythematosus,SunlightDrugs:100describedinassociationwithdruginducedlupusEpstein-BarrvirusAbnormalitiesofapoptosisAbnormalsignaltransduction:tolllikereceptorsCytokinepatterns:interferonsignature;decreasedinterleukin2fromTcellsGenes:CRPandserumamyloidPgenes,FcRreceptors,programmedcelldeathOccupationalexposure:silica,pesticides,mercury,3,LN的发病机制,抗DNA抗体和免疫复合物诱导肾脏损伤,B淋巴细胞产生具有致病性的抗DNA抗体等自身抗体,体内核小体增多或异常核小体出现,辅助性T淋巴细胞参与激活B淋巴细胞,4,5,TheglomerularpatternsofinjuryinSLE.,6,Internationalsocietyofnephrology/renalpathologysocietyclassificationoflupusnephritis(2003),7,8,9,10,Diffuseproliferativeglomerulonephritis(DPGN),11,Thelesionoffocalsegmentalproliferativelupusnephritis(FSGN),12,13,Membranousglomerulonephritis(MGN)oflupus,14,15,肾病综合征型最常见单纯型肾炎型无症状蛋白尿或血尿型较常见，轻系膜或局灶节段型急进性肾炎综合征型少见类似于急进性肾小球肾炎慢性肾炎综合征型病理：弥漫增生型肾小管综合征肾小管酸中毒，水肿，高血压，夜尿增多抗磷脂抗体型大小动静脉血栓及栓塞，习惯性流产，血小板,肾脏表现,16,肾病综合征型最常见单纯型肾炎型无症状蛋白尿或血尿型较常见，轻系膜或局灶节段型急进性肾炎综合征型少见类似于急进性肾小球肾炎慢性肾炎综合征型病理：弥漫增生型肾小管综合征肾小管酸中毒，水肿，高血压，夜尿增多抗磷脂抗体型大小动静脉血栓及栓塞，习惯性流产，血小板,肾脏表现,17,全身表现发热和疲乏皮肤与粘膜蝶形红斑，口腔溃疡，脱发关节和肌肉关节痛多为对称性，游走性，可有晨僵血液系统贫血，白细胞减少，血小板减少浆膜炎胸膜炎，心包炎，腹膜炎肺部肺实质，肺间质心脏心脏增大，心肌炎，心律失常，少数心绞痛，心肌梗死消化系统恶心，呕吐，腹痛，腹泻或便秘，腹泻常见神经系统多表现为癫痫和神经精神损害,肾外表现,18,2019/12/13,19,免疫学检查,OnehundredsixteenautoantibodiesweredescribedinSLEpatients.Theseincludeautoantibodiesthattargetnuclearantigens,cytoplasmicantigens,cellmembraneantigens,phospholipid-associatedantigens,bloodcells,endothelialcells,andnervoussystemantigens,plasmaproteins,matrixproteins,andmiscellaneousantigens.Thetargetofautoantibody,theautoantigenproperties,autoantibodyfrequenciesinSLE,aswellasclinicalassociations,andcorrelationwithdiseaseactivityaredescribedforall116autoantibodies.,20,与SLE相关的主要自身抗体,21,SLE的诊断,22,1992年ACR对1982年SLE诊断标准重新修订，将免疫学异常中的LE细胞阳性取消，并将梅毒血清实验假阳性6个月改为抗心磷脂抗体阳性。国内SLE诊断在1982年SLE诊断标准基础上加入狼疮带实验阳性和补体C3低于正常两个条件13项中符合4项或4项以上可确诊。,23,狼疮性肾炎的诊断,肾活检示WHOb，局部增生或弥漫增生性肾炎，膜性肾病。一年后肌酐清除率下降30%24小时尿蛋白定量1g持续性血尿，且尿红细胞5个/HP,24,狼疮活动性评估,下面每项记一分：发热关节炎浆膜炎典型皮疹神经精神症状脱发全身中毒症状尿常规异常血沉50mm/h贫血白细胞减少血小板减少心电图显示心肌受损低补体血症LE细胞阳性ANA1：80抗dsDNA阳性总分3分无活动，45分轻度活动，67分中度活动，9分重度活动,25,LN,静脉注射大剂量免疫球蛋白（IVIG）,个体化治疗方案,血浆置换及免疫吸附法,狼疮肾炎的中西医结合治疗,其他（降压，抗凝，消肿）,免疫抑制治疗,治疗,26,SummaryofbothestablishedtherapiesandnoveltherapiesforSLE,27,糖皮质激素(Corticosteroids),PrednisoneisstandardtherapyforthemanagementofpatientswithmoderateandsevereSLEorinthoseinwhomNSAIDsand/orHCQareineffective.Severediseaseflaresarecommonlymanagedwitheitherhighdoseoralprednisoneorintravenousinfusionsofmethylprednisone,althoughtheoptimaldoseregimenremainscontroversial.Arecenttrialconfirmedthat500mgofintravenousmethylprednisonedailyfor3dayswasassafeandeffectiveas1gdaily,28,细胞毒药物,Cyclophosphamideisthemoststudiedagentforthemanagementoflupusnephritis.Itremainsthegoldstandardandisusuallyusedinconjunctionwithcorticosteroids.Thesideeffectsofthisagent(especiallyinfertility,malignancy,hemorrhagiccystitisandinfection)havedrivendebateastotheoptimalregimen.Morerecentlyithasbeenadministeredasintermittentintravenousinfusions,inpreferencetocontinuousdailyoraluse,becauseofanimprovedsafetyprofile,especiallyareductionintheincidenceofcystitis.Althoughitisveryeffectiveininducingdiseaseremission,longtermfollowuphasshownthatnephriticflaresarecommonwithcessationoftherapy,hencemaintenancetherapyisrequired.Otherimmunosuppressiveagentsarepreferredformaintainingremission,suchasazathioprineandmorerecentlymycophenolatemofetil,becauseoftheirgreatersafety.,Azathioprine,apurineanalogue,hasanestablishedroleinthetreatmentofSLE,paricularlyasacorticosteroid-sparingagent.WhileithassuperiorefficacytoPrednisoneinthetreatmentofdiffuseproliferativelupusnephritis,itislesseffectivethancyclophosphamide.Onemajoradvantageisthatitcanbeusedsafelyinpregnancy,29,环孢素,ThisimmunosuppressivedrughasbeenusedsuccessfullyasasteroidsparingagentinSLE.Someclinicaltrialshaveindicatedaroleinthemanagementofpatientswithmembranouslupusnephritis.Itsuseislimitedbyitssideeffects,especiallyrenalimpairment,hypertension,hypertrichosisandgumhypertrophy.,30,霉酚酸酯,Thisimmunosuppressivedrughasbeenusedforseveralyearsinhumanorgantransplantation.Theactivemetaboliteofmycophenolateisaninhibitorofpurinesynthesis.MycophenolateblockstheproliferationofactivatedTandBlymphocytes.Ithasbeencomparedtocyclophosphamideinanumberofcaseseriesforthetreatmentoflupusnephritis.Arandomisedtrialpublishedin2000compared12monthsofmycophenolateandprednisonewith6monthsofcyclophosphamideandprednisonefollowedby6monthsofazathioprineandprednisoneinforty-twopatientswithproliferativenephritis.MycophenolatewasfoundtobeaseffectiveandbettertoleratedthancyclophosphamidewithnoreportsofalopeciaorLeucopeniaIntriguingly,areviewarticlein2002statedrelapseofnephritisoccurredmorecommonlyinthemycophenolategroup,31,雷公藤,有抑制淋巴，单核细胞及抗炎作用，不良反应为对性腺的毒性如出现月经减少，停经，精子活力及数目降低，皮肤色素沉着，指甲变薄软，肝损，胃肠道反应。,32,血浆置换Plasmapheresis(orplasmaexchange),血浆置换是指将全血分离成血浆和细胞成分（红细胞，白细胞，血小板），然后遗弃患者血浆，用健康人血浆或血浆代用品予以替补。现代观点主要是先分离出血浆，通过模式滤过，离心沉淀和免疫吸附等手段将分离血浆中的相关治病因子（如自身抗体，免疫复合物，骨髓瘤轻链，胆固醇相关的脂蛋白等等）清除后回输相应的血液成分。主要用于以下三种肾脏病原发性急进性肾小球肾炎原发性弥漫增生性肾小球肾炎肺出血-肾炎综合征（Goodpasture综合征）,33,Intravenousimmunoglobulin(IVIg),Intravenousimmunoglobulin(IVIg)isatherapyintendedforthetreatmentofimmune-deficiencystatesandimmune-mediateddiseases.Inrecentyears,manyreportsoftheuseofIVIginsystemiclupuserythematosus(SLE),amulti-systemicautoimmunedisease,havebeengathered.AsthetreatmentofSLEoftenincludesimmunosuppressivedrugs,IVIgoffersinadditiontoitsimmunomodulatoryproperties,alsosomeprotectionfrominfectionstotheseimmunodeficientpatients.TheexperienceofIVIguseinSLEbegangraduallywiththetreatmentofseveremanifestationsofthediseasenotrespondingtoothertherapeuticmeansi.e.asasalvage,34,预后,35,参考文