NephroticSyndromeDepartmentofPrdiatrics,TongjiHospitalNephroticSyndrome

DefinitionEtiologyPathologyPathophysiologyClinicalManifestationLaboratoryDataDiagnosisTherapyandPrognosis

Male4yearsand6monthsoldComplaintofedemaandoliguriaDefinition:NephroticCriteria

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

causes―DIAMONDMinimalChangeNephropathy(MCN)LittleornomicroscopicabnormalityAbsenceofimmunecomplexesEffacementofepithelialfootprocessOccasionallymesangialhypercellurity

MCN:normalinLMMCN:effacementofepithelialfootprocessinEMMesangialproliferativeglomerulonephritis(MsPGN)

MesangialproliferationandexpansionIgG,C3andsometimesIgA,IgMdepositsinmesangialstalkElectron-densedepositsinmesangialorparamesangialareasMsPGN:

MesangialproliferationandexpansionIgGandC3depositsinmesangialMesangialproliferativeglomerulonephritis(MsPGN)

MesangialproliferationandexpansionIgG,C3andsometimesIgA,IgMdepositsinmesangialstalkElectron-densedepositsinmesangialorparamesangialareasFocalsegmentalglomerulosclerosis(FSGS)FocalandsegmentalcapillarycollapseandmesangialsclerosisDepositsofIgMorC3intheglomeruliLossofvisceralepithelialcellpodocytes,duplicationofthebasalGBMlamina,separationofepithelialcellfromGBMMembranousNephropathy(MN)DiffuseGBMthickening,characteristicGBMspikesSubepithelialdepositofIgGandC3Membraneproliferativeglomerulonephritis(MPGN)MesangialproliferationandexpansionSubendothelialmesangialinterposition,tramtrackapperanceMesangialandsubendothelialdepositsofIgGandC3Pathophysiologyofnephroticsyndrome

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

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

Edema

Proteinuria

Nareabsorptionindistalrenaltubules

Naandwaterretention

Edema

Hypoalbuminemia

intravascularoncoticpressure↓(25mmHg→6-8mmHg)

Fluidextravasation

hypovolemia

ADHandaldosterone

Waterandsaltretension

Edema

MCN:pathogenesisofhypoalbuminemiaMCN:pathogenesisofhyperlipidemiaHypoalbuminemia→hypaticsynthesisoflipid↑→hyperlipidemiaClinicalManifestation

Simplenephrosis:2--7y,massiveedemainfaceandparaorbitalareas,ascites,pleuraleffusion,lossofappetite,nauseaandvomiting,inertiaandlethargyNephriticnephrosis:>7y,moderateedema,grosshematuria,hypertensionComplications:Complications(1)Infection:URI,peritonitis,cellulitisandetc

IgG

,IgA

,Complement

WBCfunction

LackofZnandothertraceelementsHypercoagulablestateandthrombosis

HigherconcentrationofⅤ,Ⅶ,Ⅷ,ⅩLowerlevelofanticoagulantsubstance:antithrombinⅢ，proteinS,proteinCOvervigorousdiuresisHigherbloodviscosity,increasedplateletaggregationRoleofcorticosteroidsComplications(2)Electrolyteimbalance:hyponatrimia,hypokalemia,hypercalcemiaSalt-depleteddietOvervigorousdiuresisExtrarenallossProtein-boundcalciumlossfromurineSteroidsinducedhypocalcemiaARF:pre-renalHypovolemicshockOthers:growthfailureLaboratoryData(1)ESR:simplenephrosis>100mm/h,nephriticnephrosis<100mmHgSerumpreoteinelectrophoresis:

2

,

,

insimplenephrosisbut

innephriticNephrosisImmunoglobulin:IgG

,IgA

,IgM

IgA>IgM,C3

nephriticnephrosisIgM>IgA,normalC3

simplenephrosisLaboratoryData(2)Renalfunction:usuallynormalUrineproteinpattern:simplenephrosis

albuminnephriticnephrosis

IgG,albuminandothersRatioofUIgG/Ualbuminsimplenephrosis

<1nephriticnephrosis

>1DiagnosisanddifferentialdiagnosisIdiopathicorsecondaryMCNornon-MCNimportanceofrenalbiopsyTreatmentofNSGeneralprincipleAnticoagulationCorticosteroidsImmunosuppressiveagentsChinesetraditionalmedicineGeneralprincipleLowsaltdiet(2g/d),appropriateproteinintake(2-3g/kg/d)AvoidinginfectionDiuresis:Thiazide–DHCT2mg/kg/dAntisterone2-4mg/kg/dDextran10-20ml/kgfollowedbyLasixat2mg/kgAnticoagulation

Dipyridamole:5mg/kg/dHeparin:0.5-1mg/kg/d×7-10dWarfarin:initialdose:2.5mgTid×3-5dSubsequentdose:2.5-10mg/dbasedonPTCorticosteroidsShortcourse: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%Steroidstreatmentresponse

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

Immunosuppressiveagents(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/mlImmunosuppressiv