Nephrotic-Syndrome教学讲解课件

NephroticSyndromeNephroticSyndrome1NephroticSyndrome

DefinitionEtiologyPathologyPathophysiologyClinicalManifestationLaboratoryDataDiagnosisTherapyandPrognosis

NephroticSyndrome

Definition2Male4yearsand6monthsoldComplaintofedemaandoliguriaMale3Definition:NephroticCriteria

MassiveproteinuriaISKDC:>40mg/m2/hrCAN:>+++trice/2wor>50-100mg/kg/24hrMendoza:UrineProtein/Cr≥2.0Hypoalbuminemia:<30g/LHyperlipidemia:Cholesterol>5.72mmol/LEdemaDefinition:NephroticCriteri4Definition:NephriticCriteriaHematuria:RBC++(>10/HP),trice/2wHypertension:>130/90mmHginchildrenover7y>120/80mmHgin3-6ychildren>110/70mmHgin<3ychildrenAzotemia:BUN>6.4mmol/L,Cr>133umol/LHypocomplementemia:C3<0.8/LDefinition:NephriticCriteri5DefinitionNephriticNephrosis:nephroticcriteriawithatleastonenephriticcriteriaSimplenephrosis:nephroticcriteriawithoutnephriticcriteriaDefinitionNephriticNephrosis:6EtiologyCongenitalNS:rareIdiopathicNS:majoritySecondaryNS:manycausesespeciallyin<3yor>13ypatients

causes―DIAMONDEtiologyCongenitalNS:rare7SecondaryNS:DIAMONDInfection:APSGN,HBV,HIV,shuntnephropathy,refluxnephropathy,leprosy,syphilis,schistosomiasis,hydatiddiseaseDrug,Toxic,Allegy:mercury,snakevenom,vaccine,pellicillamine,Heroin,gold,NSAID,captopril,probenecid,volatilehydrocarbonsNeoplasma:Hodgkin’sdisease,carcinoma(renalcell,lung,neuroblastoma,breast,andetc)Autoimmuneorcollagen-vasculardiseases:SLE,Hashimoto’sthyroiditis,EMC,HSP,VasculitisGeneticDisease:Alportsyn.,Fabrysyn.,Nail-patellasyn.,Sicklecelldisease,Amyloidosis,CongenitalnephropathyMetabolicdisease:DiabetesmellitusOthers:Chronictransplantrejection,congenitalnephrosclerosisSecondaryNS:DIAMONDInfectio8Pathology

PrimaryNS:MinimalChangeNephropathy(MCN):80%

Mesangialproliferativeglomerulonephritis(MsPGN):10-12%Focalsegmentalglomerulosclerosis(FSGS):5%Others:MembranousNephropathy(MN)―mostcommoninadultsMembraneproliferativeglomerulonephritis(MPGN):2-5%Cresentglomerulonephritis:rare,Crescentglomeruli>50%SecondaryNS:dependentoncauses,APSGN,MN,FSGS,MsPGNorMPGN

Pathology

PrimaryNS:9MinimalChangeNephropathy(MCN)LittleornomicroscopicabnormalityAbsenceofimmunecomplexesEffacementofepithelialfootprocessOccasionallymesangialhypercellurity

MinimalChangeNephropathy(MC10MCN:normalinLMMCN:normalinLM11MCN:effacementofepithelialfootprocessinEMMCN:effacementofepithelial12Mesangialproliferativeglomerulonephritis(MsPGN)

MesangialproliferationandexpansionIgG,C3andsometimesIgA,IgMdepositsinmesangialstalkElectron-densedepositsinmesangialorparamesangialareasMesangialproliferativeglomer13MsPGN:

MesangialproliferationandexpansionIgGandC3depositsinmesangialMsPGN:Mesangialproliferation14Mesangialproliferativeglomerulonephritis(MsPGN)

MesangialproliferationandexpansionIgG,C3andsometimesIgA,IgMdepositsinmesangialstalkElectron-densedepositsinmesangialorparamesangialareasMesangialproliferativeglomer15Focalsegmentalglomerulosclerosis(FSGS)FocalandsegmentalcapillarycollapseandmesangialsclerosisDepositsofIgMorC3intheglomeruliLossofvisceralepithelialcellpodocytes,duplicationofthebasalGBMlamina,separationofepithelialcellfromGBMFocalsegmentalglomeruloscler16MembranousNephropathy(MN)DiffuseGBMthickening,characteristicGBMspikesSubepithelialdepositofIgGandC3MembranousNephropathy(MN)Dif17Membraneproliferativeglomerulonephritis(MPGN)MesangialproliferationandexpansionSubendothelialmesangialinterposition,tramtrackapperanceMesangialandsubendothelialdepositsofIgGandC3Membraneproliferativeglomeru18PathophysiologyofnephroticsyndromePathophysiologyofnephrotics19

MCN:InvolvementofimmunesystemNoIgorcomplementdepositAssociationbetweenallegyandidiopathicNSAbnormalitiesofhumuralandcellularimmunity:IgG↓,IgA↓,CD4/CD8↓RelapseofNStriggeredbyavarietyofminorinfectionsAutologousremissionaftermeaslesInductionofremissionbycorticosteroidsandakylatingagents

MCN:Involvementofimmunesy20MCN:pathogenesisofproteinuriaLymphacyte→29kdpeptide→glomerularpolyanion↓→proteinuriaConA→lymphacytes→60-160kdGPF→proteinurialymphacytes→13-18kdSIRS→proteinuriaGPF:glomerularpermeabilityfactorSIRS:solubleimmuneresponsesuppressorMCN:pathogenesisofproteinur21MCN:pathogenesisofedemaFFNa↓,CH2O↓

Edema

ProteinuriaNareabsorptionindistalrenaltubulesNaandwaterretention

Edema

Hypoalbuminemiaintravascularoncoticpressure↓(25mmHg→6-8mmHg)FluidextravasationhypovolemiaADHandaldosterone

WaterandsaltretensionEdema

MCN:pathogenesisofedemaFFNa22MCN:pathogenesisofhypoalbuminemia

LossofproteinfromultrafiltrationIncreasedcatabolismofproteininrenaltubulesLossfromintestineprovedby51Chromium-albumintracingMCN:pathogenesisofhypoalbum23MCN:pathogenesisofhyperlipidemiaHypoalbuminemia→hypaticsynthesisoflipid↑→hyperlipidemiaMCN:pathogenesisofhyperlipi24ClinicalManifestation

Simplenephrosis:2--7y,massiveedemainfaceandparaorbitalareas,ascites,pleuraleffusion,lossofappetite,nauseaandvomiting,inertiaandlethargyNephriticnephrosis:>7y,moderateedema,grosshematuria,hypertensionComplications:ClinicalManifestationSimple25Nephrotic-Syndrome教学讲解课件26Complications(1)Infection:URI,peritonitis,cellulitisandetc

IgG,IgA,ComplementWBCfunctionLackofZnandothertraceelementsHypercoagulablestateandthrombosis

HigherconcentrationofⅤ,Ⅶ,Ⅷ,ⅩLowerlevelofanticoagulantsubstance:antithrombinⅢ，proteinS,proteinCOvervigorousdiuresisHigherbloodviscosity,increasedplateletaggregationRoleofcorticosteroidsComplications(1)Infection:U27Complications(2)Electrolyteimbalance:hyponatrimia,hypokalemia,hypercalcemiaSalt-depleteddietOvervigorousdiuresisExtrarenallossProtein-boundcalciumlossfromurineSteroidsinducedhypocalcemiaARF:pre-renalHypovolemicshockOthers:growthfailureComplications(2)Electrolytei28LaboratoryData(1)ESR:simplenephrosis>100mm/h,nephriticnephrosis<100mmHgSerumpreoteinelectrophoresis:2,,insimplenephrosisbutinnephriticNephrosisImmunoglobulin:IgG,IgA,IgMIgA>IgM,C3

nephriticnephrosisIgM>IgA,normalC3simplenephrosisLaboratoryData(1)ESR:simpl29LaboratoryData(2)Renalfunction:usuallynormalUrineproteinpattern:simplenephrosisalbuminnephriticnephrosisIgG,albuminandothersRatioofUIgG/Ualbuminsimplenephrosis<1nephriticnephrosis>1LaboratoryData(2)Renalfunct30DiagnosisanddifferentialdiagnosisIdiopathicorsecondaryMCNornon-MCNimportanceofrenalbiopsyDiagnosisanddifferentialdia31TreatmentofNSGeneralprincipleAnticoagulationCorticosteroidsImmunosuppressiveagentsChinesetraditionalmedicineTreatmentofNSGeneralprincip32GeneralprincipleLowsaltdiet(2g/d),appropriateproteinintake(2-3g/kg/d)AvoidinginfectionDiuresis:Thiazide–DHCT2mg/kg/dAntisterone2-4mg/kg/dDextran10-20ml/kgfollowedbyLasixat2mg/kgGeneralprincipleLowsaltdiet33Anticoagulation

Dipyridamole:5mg/kg/dHeparin:0.5-1mg/kg/d×7-10dWarfarin:initialdose:2.5mgTid×3-5dSubsequentdose:2.5-10mg/dbasedonPTAnticoagulationDipyridamole:34CorticosteroidsShortcourse:2mg/kg/d→pro(-)1.5mg/kg/qod×4w→notaper,Course<8w,Relapserate(1y)=81%Standardcourse:2mg/kg/d×4w→2mg/kg/qod×4w→taper,

Course<6m,Relapserate(1y)=61%Longcourse:2mg/kg/d×4-6w→2mg/kg/qod×4-6w→taper,

Course<9-12m,Relapserate(1y)=31%CorticosteroidsShortcourse:35Steroidstreatmentresponse

highresponse:4w→proteinuria(-)response:8w→proteinuria(-)partialresponse:8w→proteinuria(+/++)steroiddependent:responsivebutrequirehighdoserelapse:proteinuria(-)→proteinuria(++orup)frequentrelapse:relapsetwice/6mortrice/1ySteroidstreatmentresponsehi36SideeffectofsteroidsGrowthfailureHypertensionposteriorsublenticularcataractsOsteoporoticbonediseaseGastriculcer→hematesis

SideeffectofsteroidsGrowth37Immunosuppressiveagents(1)CTX:2-2.5mg/kg/d×8-12w,maxiumsingledose0.1,maxiumcumulative200-250mg/kgChlorambucil:0.2mg/kg/d×8-12w,maxiumsingledose6mg,maxiumcumulativedose12-16mg/kgCyclosporinA:5-6mg/kg/d×2-6m,keepbloodconcentrationat50-150ng/mlImmunosuppressiveagents(1)CTX38Immunosuppressiveagents(2)Vincristine:0.075mg/kgweekly,maxiumsingledose<2mg6-TG(6-thioguanine):2mg/kg/d×8w,maxiumsingledose<75mgnitrogenmustard:0.1mg/kg/d×4d,mayberepeated1monthlaterazathioprine:1-2mg/kg/d×8-12wImmunosuppressiveagents(2)Vin39NewimmunosuppressiveagentsMycophenolatemofetilacid(MMF):CellceptFK506:Prograf,TacrolimusRapamycin:SirulimusSimulect,basiliximab,daclizumabFYT-720、Gusperimus、SDS-RAD

NewimmunosuppressiveagentsMy40Pulsetherapy

Methylprednisolone:15-30mg/kg×3dIndication:refractorynephrosis,LupusRPGN:cocktailprotocolFSGS:MendozaprotocolMN:Ponticelliprotocol

PulsetherapyMethylprednisolo41PrognosisGenerallygood,especiallyforMCNMsPGN:goodorpoorFSGS:50%toESRFPrognosisGenerallygood,espec42Male4yearsand6monthsoldComplaintofedemaandoliguriaMale43NephroticSyndromeNephroticSyndrome44NephroticSyndrome

DefinitionEtiologyPathologyPathophysiologyClinicalManifestationLaboratoryDataDiagnosisTherapyandPrognosis

NephroticSyndrome

Definition45Male4yearsand6monthsoldComplaintofedemaandoliguriaMale46Definition:NephroticCriteria

MassiveproteinuriaISKDC:>40mg/m2/hrCAN:>+++trice/2wor>50-100mg/kg/24hrMendoza:UrineProtein/Cr≥2.0Hypoalbuminemia:<30g/LHyperlipidemia:Cholesterol>5.72mmol/LEdemaDefinition:NephroticCriteri47Definition:NephriticCriteriaHematuria:RBC++(>10/HP),trice/2wHypertension:>130/90mmHginchildrenover7y>120/80mmHgin3-6ychildren>110/70mmHgin<3ychildrenAzotemia:BUN>6.4mmol/L,Cr>133umol/LHypocomplementemia:C3<0.8/LDefinition:NephriticCriteri48DefinitionNephriticNephrosis:nephroticcriteriawithatleastonenephriticcriteriaSimplenephrosis:nephroticcriteriawithoutnephriticcriteriaDefinitionNephriticNephrosis:49EtiologyCongenitalNS:rareIdiopathicNS:majoritySecondaryNS:manycausesespeciallyin<3yor>13ypatients

causes―DIAMONDEtiologyCongenitalNS:rare50SecondaryNS:DIAMONDInfection:APSGN,HBV,HIV,shuntnephropathy,refluxnephropathy,leprosy,syphilis,schistosomiasis,hydatiddiseaseDrug,Toxic,Allegy:mercury,snakevenom,vaccine,pellicillamine,Heroin,gold,NSAID,captopril,probenecid,volatilehydrocarbonsNeoplasma:Hodgkin’sdisease,carcinoma(renalcell,lung,neuroblastoma,breast,andetc)Autoimmuneorcollagen-vasculardiseases:SLE,Hashimoto’sthyroiditis,EMC,HSP,VasculitisGeneticDisease:Alportsyn.,Fabrysyn.,Nail-patellasyn.,Sicklecelldisease,Amyloidosis,CongenitalnephropathyMetabolicdisease:DiabetesmellitusOthers:Chronictransplantrejection,congenitalnephrosclerosisSecondaryNS:DIAMONDInfectio51Pathology

PrimaryNS:MinimalChangeNephropathy(MCN):80%

Mesangialproliferativeglomerulonephritis(MsPGN):10-12%Focalsegmentalglomerulosclerosis(FSGS):5%Others:MembranousNephropathy(MN)―mostcommoninadultsMembraneproliferativeglomerulonephritis(MPGN):2-5%Cresentglomerulonephritis:rare,Crescentglomeruli>50%SecondaryNS:dependentoncauses,APSGN,MN,FSGS,MsPGNorMPGN

Pathology

PrimaryNS:52MinimalChangeNephropathy(MCN)LittleornomicroscopicabnormalityAbsenceofimmunecomplexesEffacementofepithelialfootprocessOccasionallymesangialhypercellurity

MinimalChangeNephropathy(MC53MCN:normalinLMMCN:normalinLM54MCN:effacementofepithelialfootprocessinEMMCN:effacementofepithelial55Mesangialproliferativeglomerulonephritis(MsPGN)

MesangialproliferationandexpansionIgG,C3andsometimesIgA,IgMdepositsinmesangialstalkElectron-densedepositsinmesangialorparamesangialareasMesangialproliferativeglomer56MsPGN:

MesangialproliferationandexpansionIgGandC3depositsinmesangialMsPGN:Mesangialproliferation57Mesangialproliferativeglomerulonephritis(MsPGN)

MesangialproliferationandexpansionIgG,C3andsometimesIgA,IgMdepositsinmesangialstalkElectron-densedepositsinmesangialorparamesangialareasMesangialproliferativeglomer58Focalsegmentalglomerulosclerosis(FSGS)FocalandsegmentalcapillarycollapseandmesangialsclerosisDepositsofIgMorC3intheglomeruliLossofvisceralepithelialcellpodocytes,duplicationofthebasalGBMlamina,separationofepithelialcellfromGBMFocalsegmentalglomeruloscler59MembranousNephropathy(MN)DiffuseGBMthickening,characteristicGBMspikesSubepithelialdepositofIgGandC3MembranousNephropathy(MN)Dif60Membraneproliferativeglomerulonephritis(MPGN)MesangialproliferationandexpansionSubendothelialmesangialinterposition,tramtrackapperanceMesangialandsubendothelialdepositsofIgGandC3Membraneproliferativeglomeru61PathophysiologyofnephroticsyndromePathophysiologyofnephrotics62

MCN:InvolvementofimmunesystemNoIgorcomplementdepositAssociationbetweenallegyandidiopathicNSAbnormalitiesofhumuralandcellularimmunity:IgG↓,IgA↓,CD4/CD8↓RelapseofNStriggeredbyavarietyofminorinfectionsAutologousremissionaftermeaslesInductionofremissionbycorticosteroidsandakylatingagents

MCN:Involvementofimmunesy63MCN:pathogenesisofproteinuriaLymphacyte→29kdpeptide→glomerularpolyanion↓→proteinuriaConA→lymphacytes→60-160kdGPF→proteinurialymphacytes→13-18kdSIRS→proteinuriaGPF:glomerularpermeabilityfactorSIRS:solubleimmuneresponsesuppressorMCN:pathogenesisofproteinur64MCN:pathogenesisofedemaFFNa↓,CH2O↓

Edema

ProteinuriaNareabsorptionindistalrenaltubulesNaandwaterretention

Edema

Hypoalbuminemiaintravascularoncoticpressure↓(25mmHg→6-8mmHg)FluidextravasationhypovolemiaADHandaldosterone

WaterandsaltretensionEdema

MCN:pathogenesisofedemaFFNa65MCN:pathogenesisofhypoalbuminemia

LossofproteinfromultrafiltrationIncreasedcatabolismofproteininrenaltubulesLossfromintestineprovedby51Chromium-albumintracingMCN:pathogenesisofhypoalbum66MCN:pathogenesisofhyperlipidemiaHypoalbuminemia→hypaticsynthesisoflipid↑→hyperlipidemiaMCN:pathogenesisofhyperlipi67ClinicalManifestation

Simplenephrosis:2--7y,massiveedemainfaceandparaorbitalareas,ascites,pleuraleffusion,lossofappetite,nauseaandvomiting,inertiaandlethargyNephriticnephrosis:>7y,moderateedema,grosshematuria,hypertensionComplications:ClinicalManifestationSimple68Nephrotic-Syndrome教学讲解课件69Complications(1)Infection:URI,peritonitis,cellulitisandetc

IgG,IgA,ComplementWBCfunctionLackofZnandothertraceelementsHypercoagulablestateandthrombosis

HigherconcentrationofⅤ,Ⅶ,Ⅷ,ⅩLowerlevelofanticoagulantsubstance:antithrombinⅢ，proteinS,proteinCOvervigorousdiuresisHigherbloodviscosity,increasedplateletaggregationRoleofcorticosteroidsComplications(1)Infection:U70Complications(2)Electrolyteimbalance:hyponatrimia,hypokalemia,hypercalcemiaSalt-depleteddietOvervigorousdiuresisExtrarenallossProtein-boundcalciumlossfromurineSteroidsinducedhypocalcemiaARF:pre-renalHypovolemicshockOthers:growthfailureComplications(2)Electrolytei71LaboratoryData(1)ESR:simplenephrosis>100mm/h,nephriticnephrosis<100mmHgSerumpreoteinelectrophoresis:2,,insimplenephrosisbutinnephriticNephrosisImmunoglobulin:IgG,IgA,IgMIgA>IgM,C3

nephriticnephrosisIgM>IgA,normalC3simplenephrosisLaboratoryData(1)ESR:simpl72LaboratoryData(2)Renalfunction:usuallynormalUrineproteinpattern:simplenephrosisalbuminnephriticnephrosisIgG,albuminandothersRatioofUIgG/Ualbuminsimplenephrosis<1nephriticnephrosis>1LaboratoryData(2)Renalfunct73DiagnosisanddifferentialdiagnosisIdiopathicorsecondaryMCNornon-MCNimportanceofrenalbiopsyDiagnosisanddifferentialdia74TreatmentofNSGeneralprincipleAnticoagulationCorticosteroidsImmunosuppressiveagentsChinesetraditionalmedicineTreatmentofNSGeneralprincip75GeneralprincipleLowsaltdiet(2g/d),appropriateproteinintake(2-3g/kg/d)AvoidinginfectionDiuresis:Thiazide–DHCT2mg/kg/dAntisterone2-4mg/kg/dDextran10-20ml/kgfollowedbyLasixat2mg/kgGeneralprincipleLowsaltdiet76Anticoagulation

Dipyridamole:5mg/kg/dHeparin:0.5-1mg/kg/d×7-10dWarfarin:initialdose:2.5mgTid×3-5dSubsequentdose:2.5-10mg/dbasedonPTAnticoagulationDipyridamole:77CorticosteroidsShortcourse:2mg/kg/d→pro(-)1.5mg/kg/qod×4w→nota