儿科ppt课件 9-2北京医院-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.感染类型呼吸道感染皮肤腹膜炎泌尿系感染病原

-细菌：肺炎球菌大肠杆菌

-病毒原因：

-免疫球蛋白、补体丢失，免疫功能低下

-蛋白营养不良

-皮质激素治疗

-局部水肿引致易发感染处理：

-不主张预防用药

-感染者积极治疗2.电解质紊乱不恰当禁盐或低盐饮食利尿剂及激素应用吐泻丢失感染应激低蛋白及VitD缺乏

低钠脑水肿惊厥低钾乏力、心律失常低钙手足搐搦3.高凝状态—血管栓塞栓塞部位

肾静脉栓塞发热、腰痛、血尿（非肾小球源性）肾衰

股动脉栓塞

脑栓塞瘫痪等

肺栓塞胸痛、咯血4肾上腺危相

发病因素不恰当长期应用激素对垂体-肾上腺皮质轴的反馈抑制未合理减药,感染诱发

主要表现皮肤湿冷及大理石花纹、肢端凉、精神差或烦燥

治疗静点激素、静点白蛋白及生理盐水扩容5急性肾衰低血容量所致肾前性肾小球病变肾间质水肿间质性肾炎诱因肾血流感染水肿药物

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