兒科ppt課件 9-2北京醫(yī)院-Nephrotic Syndrome

NephroticSyndromeCapitalInstitutesofPediatricsChenChaoyingPurposeandRequirementMasterthedefinitionofNSMastertheclinicaltypesofNSMasterthetreatmentprinciplesofNS

NephroticSyndromeDefinition:1.Massiveproteinuria2.Hypoalbuminemia

Withorwithout3.Hypercholesterolemia4.Edema50mg/kg/dor3.5gm/day)+++~++++,2周3次尿蛋白/肌酐>2.0<25-30g/L>5.72mmol/L

NephroticSyndrome1.Primary2.Secondary3.Congenital

NephroticSyndrome90%-primaryglomerularabnormality(Idiopathic)Rest–partofrenalinvolvementindifferentdiseases

NephroticSyndromeIncidenceofIdiopathicForm2to7/100,000Male-to-female2-4:1inchildren1:1inadolescentsandadultsMCNS:2and5yearsofage92%remissionAdolescents:aggressiveClassification1.ClinicalSimpleNephriticHematuriaHypertensionAzotemiaComplementdecreaseClassification2.PathologicalMinimalChangeNS2.MesangialProliferationGlomeruerNephritis3.FocalSegmentalGlomerulosclerosis4.Membranousnephropathy(1%)5.MembranousProliferativeGlomeruerNephritis

PathologicalTypes

MCNSNephroticSyndrome–76%MCNS–Noglomerularabnormalitiesinlightmicroscope–

Effacementoffootprocessesinelectronmicroscopy–Minimaldepositionofmesangialmatrix–Serumcomplement(C3)normal–Circulatingimmunecomplexesabsent

PathogenesisofNS

InMCNS:

TCelldysfunctionleadstoalterationofcytokineswhichcausesalossofnegativelychargedglycoproteinswithincapillarywallInFSGS:AplasmafactorproducedbylymphocytesresponsibleMutationsinpodocyteproteins(podocin,a–actinin4)InSteroidresistantNS:MutationsinNPHS1(nephrin)&2(podocin)andWT1orACTN4(α-actinin)genes

Increasedpermeabilityofglomerularcapillarywall,whichleadstomassiveproteinuriaandhypoalbuminemia.

MassiveProteinuria-Mechanism?Lossofnegativelychargedsialoproteinsandglycoproteins?

Increasedsizeofpores?Lossoffootprocesses?Increasedexcretionordecreasedabsorption

ProteinLoss–Albumin–Thyroxine-bindingprotein–Cholecalciferol-bindingprotein–Transferrin–Metalbindingproteins–AntiThrombinIII,ProteinsC&S

Hypoproteinemia-MechanismIncreasedlossInadequatesynthesisIncreasedcatabolism

Hyperlipidemia-MechanismLossoflipoproteinlipaseenzymeinurinesynthesisoflipoproteins

Oedema-MechanismMassiveproteinuria–hypoalbuminemia-plasmaoncoticpressure->transudationoffluidfromintravascularcompartmenttointerstitialspace.Primaryretentionofwaterandsodium

ClinicalFeatures?Ageofonset:85-90%<6yrsyrs?30%adolescentsmayhaveMCNS?Onset:insidious?Initialepisode&subsequentrelapsesmayfollowminorinfectionsorinsectbites,beestings,poisonivy,etc.

ClinicalFeaturesCOMMON:

?Anorexia,irritability,abdominalpain,diarrhoeaandgenitaledema

?

Frothyurine(highconcentrationsofprotein)

?Edemamaycausedyspnea(pleuraleffusionorlaryngealedema),

?Chestdiscomfort(pericardialeffusion),arthralgia(hydrarthrosis),orabdominalpain(ascitesor,inchildren,mesentericedema).

?Edemamayobscuresignsofmusclewastingandcauseparallelwhitelinesinfingernailbeds(Muehrcke'slines).UNCOMMON:

?Hypertension,GrosshematuriaCOMPLICATIONSA.DuetoDiseaseB.DuetoTreatment

A.ComplicationsDuetoDisease

Infections:S.pneumonia,H.influenza–VPDsDisturbanceofelectrolytesThromboticcomplicationsAcuterenalfailureIron,copper,zinc,andvitaminDdeficienciesLaryngealedema-rarelyPEMduetoproteinloss1.感染類型呼吸道感染皮膚腹膜炎泌尿系感染病原

-細(xì)菌：肺炎球菌大腸桿菌

-病毒原因：

-免疫球蛋白、補(bǔ)體丟失，免疫功能低下

-蛋白營(yíng)養(yǎng)不良

-皮質(zhì)激素治療

-局部水腫引致易發(fā)感染處理：

-不主張預(yù)防用藥

-感染者積極治療2.電解質(zhì)紊亂不恰當(dāng)禁鹽或低鹽飲食利尿劑及激素應(yīng)用吐瀉丟失感染應(yīng)激低蛋白及VitD缺乏

低鈉腦水腫驚厥低鉀乏力、心律失常低鈣手足搐搦3.高凝狀態(tài)—血管栓塞栓塞部位

腎靜脈栓塞發(fā)熱、腰痛、血尿（非腎小球源性）腎衰

股動(dòng)脈栓塞

腦栓塞癱瘓等

肺栓塞胸痛、咯血4腎上腺危相

發(fā)病因素不恰當(dāng)長(zhǎng)期應(yīng)用激素對(duì)垂體-腎上腺皮質(zhì)軸的反饋抑制未合理減藥,感染誘發(fā)

主要表現(xiàn)皮膚濕冷及大理石花紋、肢端涼、精神差或煩燥

治療靜點(diǎn)激素、靜點(diǎn)白蛋白及生理鹽水?dāng)U容5急性腎衰低血容量所致腎前性腎小球病變腎間質(zhì)水腫間質(zhì)性腎炎誘因腎血流感染水腫藥物

B.ComplicationsDuetoTreatment

SteroidsCushingoidsyndromeHypertensionduetosaltretention

OsteoporosisSusceptibilitytoinfectionsGrowthfailureCateractsGlaucomaGastritisPepticulcerHypokalemiaBehaviouralchangesCrisisofadrenalglandCyclophosphamiAlopeciaLeucopeniaInfertilityHemorrhagiccystitisINVESTIGATIONS

UrineRoutineexam.:3+or4+proteinuria24hoururineprotein>3.5gmor50mg/kgUrineprotein/creatinineratio:>2.0UrineproteinselectivityHyalinecastsMicroscopichematuriain20%

HyalineCastinurine

BloodS.CholesterolS.AlbuminS.A/Gratio-reversalS.CreatinineBl.UreaS.C3andC4levelsDiagnosis4characteristics

RenalBiopsy-indications

Ageofonset<1yr.or>15yrs.FeaturessuggestiveofdiseaseotherthanMCNS[macroscopichematuria,HTN,LowC3,renalfailure]Steroidnon-responderFrequentrelapsesSteroiddependencySecondarysteroidresistancePriorcytotoxictherapyDD–Proteinlosingenteropathy–Hepaticfailure–CHF–AcuteorchronicGN–PEM

SecondaryNephroticSyndrome?

Vasculitides

–

SLE,Sarcoidosis,HSP,Rheumatoidarthritis,WagenersgranulomatosisGoofpasteursyndrome?

Metabolic

–

Amyloidosis,Myxoedema,DM?

Infections

–

Syphilis,Shuntnephritis,HepatitisBandC,CMV,HIV?

Parasitic

–

Plasmodiummalariae,Toxoplasma,Syphilis?

Drugs

–

Gold,Mercury,Penicillamine,Lithium,Ethosuccimide,NSAIDS?

Malignancies

–

Lymphomas,Carcinomas?

Congenital/Inherited

–

Alportsyndrome,Nail-Patellasyndrome

MINIMALCHANGENEPHROTICSYNDROMEFOCALSEGMENTALGLOMERULOSCLEROSISMEMBRANOUSNEPHROPATHYMEMBRANOPROLIFERATIVEGLOMERULONEPHRITIS

TypeITypeIIFREQUENCY

Children75%10%<5%10%10%Adults15%15%50%10%10%ClinicalManifestations

Age(yr)2–6,someadults2–10,someadults40–505–155–15Sex2:1male1.3:1male2:1maleM-FM-FNephroticsyndrome100%90%80%60%60%Asymptomaticproteinuria010%20%40%40%Hematuria10–20%60–80%60%80%80%Hypertension10%20%earlyInfrequent35%35%RateofprogressiontorenalfailureDoesnotprogress10yr50%in10–20yr10–20yr5–15yrMINIMALCHANGENEPHROTICSYNDROMEFOCALSEGMENTALGLOMERULOSCLEROSISMEMBRANOUSNEPHROPATHYMEMBRANOPROLIFERATIVEGLOMERULONEPHRITIS

TypeITypeIIAssociatedconditionsAllergy?Hodgkindisease,usuallynoneNoneRenalveinthrombosis,cancer,SLE,hepatitisBNonePartiallipodystrophyLaboratoryFindingsManifestationsofnephroticsyndromeManifestationsofnephroticsyndromeManifestationsofnephrotic

↑BUNin15–30%↑BUNin20–40%syndromeLowC1,C4,C3–C9NormalC1,C4,low

C3–C9ImmunogeneticsHLA-B8,B12(3.5)[?]Mutationsinpodocin,α-actinin-4,othergenesHLA-DRw3(12–32)[?]NotestablishedC3nephriticfactorNotestablishedMINIMALCHANGENEPHROTICSYNDROMEFOCALSEGMENTALGLOMERULOSCLEROSISMEMBRANOUSNEPHROPATHYMEMBRANOPROLIFERATIVEGLOMERULONEPHRITIS

TypeITypeIIRenalPathology

LightmicroscopyNormalFocalscleroticlesionsThickenedGBM,spikesThickenedGBM,proliferationLobulationImmunofluorescenceNegativeIgM,C3inlesionsFinegranularIgG,C3GranularIgG,C3C3onlyElectronmicroscopyFootprocessfusionFootprocessfusionSubepithelialdepositsMesangialandsubendothelialdepositsDensedepositsResponsetoSteroids90%15–20%MaybeslowprogressionNotestablishedNotestablished

Management-PrinciplesAdmission–Forestablishmentofdiagnosis–Forexclusionofinfection–TowaitforspontaneousremissionTreatinfectionsSupportivetherapySteroidtherapy

SupportiveCareDiet:Balancedadequateprotein(1.5–2gm/kg)Not>30%caloriesfromfatsAvoidsaturatedfatsReductioninsaltintake(1-2g/d)forthosewithpersistentedemaCalciumandVitaminDsupplementationEnsurephysicalactivity?

DiureticTherapy

TreatmentofInitialEpisodeSteroidTherapyPrednisalone2mg/kg/din2-3divideddosesfor6weeks[themostdosage80mg/d]After4-8wks,reducedose–

1.5mg/kg/dasasingledoseeveryotherdaymorningslowlytaperingin2-3months/6mons/9ThendiscontinueShorterdurationofinitialtherapyisnotrecommended.

ISKDCTerminologyRemission

Urinealbumin:NilorTracesor<4mg/m2/hrfor3consecutiveearlymorningspecimenResponseUrinefreeofproteinin4wks.(Steroidsensitive)LateResponse

Aresponsebeyond4weeks

ISKDCTerminologyRelapseProteinuria2+plusedemafor3consecutiveearlymorningspecimen(havingbeeninremissionpreviously)EarlyRelapseInitialearlyresponderswhorelapseduring8wksoftherapyFrequentRelapseTwoormorerelapsesin6mo.Or>3relapsesin1year

ISKDCTerminologySteroidDependentRelapsewhileonalternatedaysteroidtherapyorwithin14daysofstoppingprednisonetherapy,andresponsetomoresteroid.SteroidResistant:donotrespondtotheinitialtreatmentwithprednisonewithin4weeksoftherapy2mg/kg/d

(FSGS=80%,MPG=20%,MCNS–rarely)

TreatmentofRelapseRelapseoftenprecipitatedbyURIPrednisone2mg/kg/duntiltheurineisproteinfreefor3consecutivedaysThereafter–1.5mg/kg/donalternatedaysfor4wksandstop.(Totaldurationoftherapy=5to6wks.)

Managementof

FrequentRelapses,SteroidDependence,

Steroidresistance

1.Longtermalternatedayprednisone:0.5to0.25mg/kg/dasasinglemorningdoseonalternatedaysfor9–18months

Managementof

FrequentRelapses,SteroidDependence,

Steroidresistance

2.Levamisole2.0to2.5mg/kgonalternatedaysfor1-2yearsCo-treatmentwithprednisoneat1.5mg/kg/donalt.daysfor2-4weeks–graduallyreducingthedoseto0.15–0.25mg/kgfor6ormoremonths.AdverseEffects:LeucopeniaFlulikesymptomsLivertoxicityConvulsionsSkinrashes

Managementof

FrequentRelapses,SteroidDependence,

Steroidresistance

3.Cytotoxicdrugs–Cyclophosphamide(followingremission)2-3mg/kg/dfor8-12weekregimenwithalongwithprednisone(1-1.5mg/kg/d)AdverseEffects:LeucopeniaHemorrhagiccystitisAlopeciaGonadaltoxicityNausea&vomiting

Managementof

FrequentRelapses,SteroidDependence,

Steroidresistance

Cyclosporine:3-6mg/kg/dinq12hdoses(100-150mg/m2/d)combinedinitiallywithalt.dayprednisonefor12-24monthsAdverseEffects:NephrotoxicityHypertensionHypercholesterolemiaElevatedtransaminases

Managementof

FrequentRelapses,SteroidDependence,

Steroidresistance

Micophenlatemofetil(MMF):800-1200mg/m2alongwithtaperingdoseofprednisonefor12-24monthsAdverseEffects:GIdiscomfortDiarrhoeaLeucopenia

ManagementofNS

OtherDrugsUsed

ACEInhibitors:topreventproteinuriaActbyalterationofcapillarypermeabilityandreductioninglomerularhydrostaticpressureHMGcoenzyme-Areductaseinhibitorstoreduces.cholesterolAlbuminInfusion:controversialHypotensionSevereOliguriaHeperin

ManagementofNS

Immunization

Patientsonprednisonetherapyareconsideredimmunosuppressed–

avoidliveattenuatedvaccinesAllpatientsshouldreceivepneumococcalvaccine

InitialSteroidResistance

MesangialproliferativeGNFocalsegmentalglomerulosclerosis(FSGS)Membrano-proliferaiveGN(MPGN)Type1:withintactBMType2:(30%)withdensedeposits,-persistentlowserumC3,abundantimmunonglobulin&C3depositsMembranousnephropathy

InitialSteroidResistance

Trialofpulsemethylprednisone(15-30mg/kg)CTXCyclosporinAMycophenolatemofetilPROGNOSIS

OutcomeofMCNS

Moststopgettingrelapsesby11to15yrsFullrecoveryVerysmallproportion–developlatesteroidresistanceMortality:1-4%sec.toinfections&hypovolemiaPrognosisRelatedtopathologicaltypeandresponsetosteroid

90%MCNS30%non-relapse20%FSGSresponsive40%1-2relapse50%MsPGN30%freque