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1、狼瘡性腎炎治療進展SLE60%~75%狼瘡性腎炎(LN)100%病理學上改變SLE預后因素嚴重發(fā)作社會經濟地位低高AI、CI未控制的高血壓起始治療反應差依從性差種族LNMultivariateanalysisofpredictorsofgoodlongtermrenaloutcomevariantsPOR95%CLAge(<30years)Gender(F)Baselinediastolicpressure(<90mmHg)Baselineserumcreatinine(<1.4mg/dL)Baselineserumalbumin(<3g/dL)Baseline24hprotein
2、uria(<3g)WHOclasses(IIIorV)Activityindex(<10)Chronicityindex(<1)Treatment(HDIVCTX)ACEIused(yes)Serumcreatinineat6months(drop)0.0114.92.0~11.824hproteinuriaat6months(<1g)0.038.31.2~34.4LN選擇治療依據臨床表現(蛋白尿、血尿、管型)腎活檢(分型)腎活檢+臨床表現問題腎活檢少僅憑LN臨床表現:局限性,盲目性LN病理學分型演變1974年WHO(I~V)1982年WHO(I~VI)1995年WHO(I~VI)
3、2003年LN分型(I~VI)WeeningJJ,etal.KidneyInt2004,65:521-530.InternationalSocietyofNephrology/RenalPathologySociety(ISN/RPS)2003classificationoflupusnephritisClassIMinimalmesangiallupusnephritisClassIIMesangialproliferativelupusnephritisClassIIIFocallupusnephritisClassIII(A)ClassIII(A/C)ClassIII(C)C
4、lassIVDiffuselupusnephritisClassIV-S(A)ClassIV-G(A)ClassIV-S(A/C)ClassIV-(A/C)ClassIV-S(C)ClassIV-G(C)ClassVMembranouslupusnephritisClassVIAdvancedscleroticlupusnephritisClassIIClassIII(A)ClassIII(A)ClassIV-G(A)ClassIV-S(A)ClassIV-G(A)ClassIV-G(A/C)ClassIV-G(A/C)ThromboticmicroangiopathyClassV
5、IClassIVandV(A/C)ClassVLN治療問題Overtreatment!I,II,IIIUndertreatment!IV,VLN治療原則EarlyrecognitionCorrectevaluationStringentobjectivesPromptremissionMaintainremissionAvoidrenalimpairmentMinimaltoxicityLN治療誘導治療+維持治療誘導、維持治療藥物選擇?劑量?給藥途徑?療程?療效?毒性?復發(fā)?誘導治療GCCYC(NIH“highdose”,StThomasEULAR“l(fā)owdose”Cellcept
6、Rituximab?GC+CYC,GC+Cellcept,GC+?維持治療CYCGCAzaCellcept?CQ+MTX給藥途徑OP(continuousorpulse)CYCIV(pulse)Aza,Cellcept藥物劑量療程NIHGCOPandIV(1g/m2/m12~36月)CYC0.75~1g/m2/m×6月緩解后3月一次維持一年AustinHAetal.NEnglJMed,1986,314:614-619ELNTHDIVCYCLDIVCYC0.5g×6q2wAzaw44Azaw122mg/kg/d2mg/kg/dGC(MP)750mg/d×30.5mg/kg.d(4w)
7、2.5mg(2w)5~7.5mg/d(≥30months)HoussiauFAetal.ArthritisRheu,2002;8:2121-2131.藥物劑量療程藥物劑量療程GC0.8mg/kg/d10mg/dCYC2.5mg/kg/d×6月P10mg/d+Aza1~1.5mg/kg/dChanTMetal.Lupus2005,14:265-272.6月藥物劑量療程MMF2g/d×6mCYC2.5g/kg/d×6mvs1g/d×6mAza1.5g/kg/d×6mPre