內(nèi)科學(xué)腎小球疾病

GlomerularDiseasesForInternalMedicine第1頁Theperipheralportionofaglomerularlobule第2頁GlomerularDiseasesClassificationPrimarySecondaryHereditary第3頁P(yáng)athogenesis第4頁ImmunologicglomerularinjuryHumoralantibody-mediatedCellularantibody-independent第5頁Antibody-mediatedCirculatingautoantibodieswithintrinsicautoantigens:eg.anti-GBMdiseaseInsituformationofimmunecomplexs/circulationgantibodieswithextrinsicantigensthathavebeen“planted”withintheglomerulus:eg.PostinfectiousglomerulonephritisANCA/AECAassociated:nodisernibleimmunecomplexesintheglomerularparenchyma第6頁Cellularantibody-independentglomerularinjuryLesswelldefinedInitiatorsofinjuryinpauci-immuneglomerulonephritis,whichsharethedownstreammediatorswiththeantibody-dependentinjurySolublefactorsfromTcells:inMCDandprimaryFSGS第7頁NonimmunologicglomerularinjuryMetabolicHemodynamictoxic第8頁

immunologichumoralcellularnon-immunologicinflammationGlomerularinjury第9頁Clinicopathologiccorrelatesinglomerulardisease第10頁Majorclinicopathologicentities(cont’d)NephroticsyndromeGlomerularfiltrationbarrieraffectedNephrotic-rangeproteinuria>=3.5g/24hHypoalbuminemia,edema,hyperlipidemia,andlipiduria,andaprothromboticstateMembranousglomerulopathyMinimalchangedisease(MCD)FSGSMembranoproliferative:hybridlesionofnephriticandnephroticfeatures第11頁OthersGlomerulardepositiondiseases:extravasculardepositionofparaproteinorfibrillarmaterialThromboticmicroangiopathies:thrombiwithintherenalmicrovasculature第12頁P(yáng)rimaryinsultInflammatory√Metabolic√Hemodynamicormechanic√ToxicInfectiousMayoverlapMayinducesimilarclinicopahtologicpresentations第13頁病變部位系膜mesangium系膜細(xì)胞mesangialcell系膜基質(zhì)mesangialmatrix基膜basementmembrane上皮細(xì)胞足細(xì)胞podocyte、足突footprocess內(nèi)皮細(xì)胞第14頁Theperipheralportionofaglomerularlobule第15頁

基本病變

增生proliferation硬化sclerosis第16頁1.輕微腎小球病變（MinorLesion)

無特異性病變

光鏡下可見輕度系膜細(xì)胞增生和

系膜基質(zhì)增多輕微病變腎病

minimalchangedisease，MCD輕度系膜增殖性腎小球腎炎毛細(xì)血管內(nèi)增殖性腎小球腎炎恢復(fù)期其他第17頁MCD

（左）正常，（右）上皮細(xì)胞足突廣泛融合、消失第18頁2.局灶節(jié)段性病變(1)局灶節(jié)段性增殖性腎小球腎炎focalandsegmentalproliferativeglomerulonephritis

(2)局灶節(jié)段性腎小球硬化

focalandsegmentalglomerulosclerosis,FSGS第19頁局灶性腎小球腎炎第20頁3.彌漫性腎小球腎炎

(diffusiveglomerulonephritis)(1)膜性腎病membranousnephropathy,MN

腎小球基底膜

第21頁membranousnephropathy

（左）正常，（右）上皮下免役復(fù)合物沉積（D），GBM增厚，釘突形成（S），上皮細(xì)胞足突融合第22頁(2)增殖性腎小球腎炎

proliferativeglomerulonephritis系膜增殖性腎小球腎炎

mesangialproliferativeglomerulonephritisMsPGN

腎小球系膜IgA腎病IgAnephropathy非IgA腎病IgG沉積為主IgM腎病第23頁mesangialproliferativeglomerulonephritis（左）正常，（右）系膜細(xì)胞和基質(zhì)增生，電子致密物（D）沉積第24頁毛細(xì)血管內(nèi)增殖性腎小球腎炎

endocapillaryproliferativeglomerulonephritis

系膜+內(nèi)皮細(xì)胞第25頁endocapillaryproliferativeglomerulonephritis

（左）正常，（右）內(nèi)皮（E）和系膜（M）細(xì)胞增生，上皮下駝峰狀電子致密物（D）沉積第26頁系膜毛細(xì)血管性腎小球腎炎

mesangiocapillaryglomerulonephritis

又稱膜增殖性腎小球腎炎

membranoproliferativeglomerulonephritis

系膜+基底膜致密沉積物性腎小球腎炎

densedespositglomerulonephritis

電子致密沉積物第27頁mesangiocapillaryglomerulonephritis

（左）正常，（右）系膜增生（M），電子致密物（D），廣泛插入（I）第28頁新月體性腎小球腎炎

cresenticglomerulonephritis又稱毛細(xì)血管外腎小球腎炎

extracapillaryglomerulonephritis

腎小球囊上皮細(xì)胞(3)硬化性腎小球腎炎

sclerosingglomerulonephritis第29頁cresenticglomerulonephritis

（左）正常，（右）GBM斷裂，纖維蛋白漏出(F)，上皮細(xì)胞增生(E)，單核巨噬細(xì)胞浸潤(rùn)(P)，新月體形成第30頁4.未分類旳腎小球腎炎u(yù)nclassifiedglomerulonephritis第31頁Clinicalpresentations第32頁ClinicalclassificationAcuteglomerulonephritis,AGNRapidlyprogressiveglomerulonephritis,RPGNChonicglomerulonephritis,CGNNephroticsyndrome,NSLatentglomerulonephritis,asymptomatichematuriaand/orproteinuria第33頁AcutenephriticsyndromeSuddenonset(daystoweeks)NephriticurinarysedimentHematuria:Redbloodcasts,dysmorphicredbloodcellsSubnephroticproteinuria(<3.0g/24h)Extracellularfluidvolumeexpansion,edema,andhypertensionAcuterenalfailureandoliguria第34頁Acutenephriticsyndrome(cont’d)ProliferativeglomerulonephritisInfiltrationoftheglomerulartuftbyneutropilsandmonocytes,followedbyproliferationofresidentendothelialandmesangialcellsEndocapillaryproliferativeGN第35頁Streptococcalinfection(PSGN)

-symptomsandsigns1-3weeksafterpharyngitisor1-4weeksafteraskininfection(impetigo)NephritogenicstrainofgroupAbeta-hemolyticstreptococcusNephriticsyndromewitholiguricARF,ormilderHeadache,anorexia,nausea,vomiting,andmalaise,flankorbackpain第36頁P(yáng)SGN–labinvestigationsSerumcreatinineoftenmildlyelevatedC3andCH50depressedwithin2weeksin~90%patients,C4characteristicallynormal;returntonormalwithin6-8weeksTransienthypergammaglobulinemiaandmixedcryoglobulinemiaCirculatingantibodiesagainststreptococcalexoenzymessuchasASO第37頁P(yáng)SGN-pathologyDiffuseproliferativeGNCrescentsuncommonExtraglomerularinvolvementmildIFmicroscopy:diffusegranulardepositionofIgGandC3EM:largeelectron-densedepositsinthesubendothelial,subepithelialandmesangialareas第38頁P(yáng)SGN-treatmentEliminatingthestreptococcalinfectionwithantibioticsDiureticsandantihypertensiveagentstocontrolECFvolumeandBPSpontaneousresolutionwithin6-8weeksinchildren>20%adultsmayhavepersistentproteinuriaand/orcompromiseofGFR第39頁RPGNOverweekstomonthsNephriticurinarysediment,subnephroticproteinuriaandvariableoliguria,hypervolemia,edema,andhypertensionCrescenticGNCrenscentscanalsodevelopconcomitantlywithproliferativeGN,membranousGNandotherGN第40頁RPGN-Immunofluorescencemicroscopyanti-GBMdis---morediscretelineardepositionofIgalongtheGBMimmunecomplexGN---scatteredgranulardepositsofimmunoglobulinpauci-immuneGN---paucityorabsenceofIg第41頁RPGN-SerologicmarkersDepressedC3level---TypeIIanti-GBMantibody---TypeIANCA---TypeIIIMayoverlap第42頁Anti-GBMdisease(Goodpasture’ssyndrome)Antibodytoa3chain(noncollagenousdomain)oftypeIVcollagen,whichpreferentiallyexpressedinglomerularandpulmonaryalveolarbasementmembraneRPGN/crescenticGN,hematuria,nephriticurinarysediment,subnephroticproteinuria50-70%havelunghemorrhagewithhemoptysisorseverealveolarhemorrhage第43頁Anti-GBM–labtestsAnti-GBMantibodiesRenalbiopsy,goldstandardfordiagnosisofanti-GBMnephritisDiffuseproliferativeGNFocalnecrotizinglesionsCrescentsin>50%ofglomeruliLinearribbon-likedepositionofIgGalongtheGBM第44頁pauci-immuneRPGNIdiopathicrenal-limitedcrescenticGNMicrosopicpolyangiitisnodosaWegener’sgranulomatosisChurg-strausssyndromeAll-encompassingterm:ANCA-associatedsmallvesselvasculitis第45頁ANCA-associatedrenaldiseaseLethargy,malaise,anorexia,weightloss,fever,arthralgias,myalgiasElevatedESR/CRP,leukocytosis,thrombocytosis,normochromicnormocyticanemia,complementleveltypicallynormalNephriticurinesedimentandsubnephroticproteinuriaRenaldysfunctionBiopsy:focalsegmentalnecrotizingGNwithcrescentformationPaucityorabsenceofIg,complementandimmunedeposits第46頁RPGN

I型II型

III型抗基膜抗體型免疫復(fù)合物型非免疫復(fù)合物型IF線樣、沿基膜顆粒樣、系膜（-）區(qū)和基膜

GBM抗體（+）C3、CIC

70%-80%為微血管炎ANCA陽性

青、中年中、老年中、老年

我國(guó)多見第47頁treatmentGlucocorticoid,pulsetreatmentandmaintenancetreatmentCTXorAZAplasmaphereses,immunoadsorptionBetterprognosisinrelativelyearlycases(Scr<442mmol/L)Relapsesnotunusual第48頁Nephroticsyndrome,NSProteinuria>3.5g/24hHypoalbuminemia<3.0g/LEdemaHyperlipidemia,lipiduriaandhypercoagulability第49頁MainentitiesofNSMinimalchangedisease,MCDFocalandsegmentalglomerulosclerosis,FSGSMembranousglomerulopathy,MNMsPGNMembranoproliferativeglomerulonephritis,MPGNDiabeticnephropahy,DNAmyloidosis,MM第50頁Complications---thrombosis

deepveinthrombosis

renalveinthrombosisSuddenonsetofflankorabdominalpainGrosshematuriaAleft-sidedvaricoceleIncreasedproteinuriaAcutedeclineinGFRPaticularlycommoninMN/MPGN/Amyloidosis第51頁OthercomplicationsProteinmalnutritioninfection第52頁NS-treatmentSpecifictreatmentoftheunderlyingdiseaseGlucocorticoid,immunosuppressionGeneralmeasuresofproteinuriacontrolACEI/ARBNephroticcomplicationscontrolandprevention第53頁Sensetivityofsteroidprednisone(prednisolone)1mg/kg/d8w

negetive

proteinuriaremainpositive

relapseduringtaper

sentsetiveSteroid-dependentresistance第54頁NScomplicationscontrolEdemaSaltrestriction1-2g/d;judicioususeofloopdiuretics;LipidloweringHMGCoAreductaseAnticoagulationIndications:deepvenousthrombosis,arterialthrombosis,pulmonaryembolism第55頁Minimalchangedisease,MCD80%ofNSinchildrenyoungerthan16yo,20%inadultsGlomerularsizeandarchitecturenormalbylightmicroscopyIFmicroscopynegativeforIgandC3EMcharacteristicdiffuseeffacementoffootprocessesofvisceralepithelialcells第56頁MCD-proteinuriaselectivitySelectiveproteinuriainchildrenwithalbuminprincipallyandminimalamountsofhighermolecularweightprotiensSelectivitypoorinadultssuggestingmoreextensiveperturbationofmembrane第57頁MCD-treatmentHighlysteroid-responsiveGenerallyexcellentprognosisRemissionafter8weeksofhigh-doseoralglucocorticoids:90%inchildrenand50%inadults第58頁MCD-treatment(cont’d)RelapsescommonfollowingwithdrawalofglucocorticoidsAlkylatingagentsreservedforsteroid-resistant,steroid-dependentorfrequentlyrelapsing:CTX,chlorambucil,azathioprine,cyclosporine第59頁Focalsegmentalglomerulosclerosis,FSGSSclerosiswithhyalinosisinvolvingportions(segmental)offewerthan50%(focal)ofglomeruliIdiopathicFSGS:Nephroticsyndrome(2/3)orsubnephroticproteinuria(1/3),nonselectiveHypertension,mildrenalinsufficiency,abnormalurinesediment第60頁FSGS(cont’d)IdiopathicSecondary:apotentiallong-termconsequenceofnephronloss(>50%)fromanycauseCongenitaloligomeganephronia,extensivesurgicalablationofrenalmass,refluxnephropathy,GN,interstitialnephritis,sicklecelldisease,ischemia,cyclosporinenephrotoxicity,rejectionofallograft第61頁FSGS-treatmentRenalprognosisrelativelypoorRemissionratesfor8weekglucocorticoids:20-40%,upto70%forprolongedtherapy(16-24weeks)Immunosuppressants:CTX,cyclosporine,MMFPoorprognosticfactors:hypertension,abnormalrenalfunction,persistentheavyproteinuria第62頁Membranousglomerulopathy(membranousnephropathy,MN)Peakincidence30-50yearsofageMale:femal2:1Namedafterlightmicrscopic:diffuseGBMthickening>80%representswithNS,nonselectiveMicroscopichematuria50%第63頁MN-pathologyLM:DiffusethickeningofGBMwithoutinflammationorcellularproliferationIF:granulardepositionofIgG,C3andterminalcomponentsofcomplementsalongtheglomerularcapillarywall第64頁MN-pathogenesisIdiopathicMNincompletelyunderstoodImmunedepositssuggestinganimmuneprocess1/3withsystemicdisease:SLE,infectionssuchashepatitisB,malignancy,drug(eg.goldandpenicillamine)第65頁MN-treatmentandprognosisremitsspontaneouslyandcompletelyinupto40%another30to40%repeatedrelapsesandremissionsThefinal10to20%slowprogressivedeclineinGFRthattypicallyculminatesinESRDafter10to15yearsPoorprognosisindicators:malegender,olderage,hypertension,severeproteinuriaandhyperlipidemia,andimpairedrenalfunctionControlledtrialsofglucocorticoidshavefailedtoshowconsistentimprovementinproteinuriaorrenalprotection.Cyclophosphamide,chlorambucil,andcyclosporinehaveeachbeenshowntoreduceproteinuriaand/orslowthedeclineinGFRinpatientswithprogressivediseaseinsmalloruncontrolledstudies.第66頁Membranoproliferativeglomerulonephritis,MPGNthickeningoftheGBMandproliferativechangesonlightmicroscopytypeIMPGN:subendothelialandmesangialdepositsonelectronmicroscopythatcontainC3andIgGorIgM;rarely,IgAdepositstypeIIMPGN(densedepositdisease):electron-densedepositswithintheGBMandotherrenalbasementmembranes(shownbyelectronmicroscopy)thatstainforC3,butlittleornoimmunoglobulin.第67頁MPGNtypeI-clinicalfeaturesTypeIAnimmune-complex(IC)GNnephroticsyndrome,activeurinarysediment,andnormalormildlyimpairedGFR.C3levelsusuallydepressed,andC1qandC4levelsborderlineorlowAssociatedwithinfections,systemicICdiseases(SLE,cryoglobulinemia),malignancies50%ofpatientsreachESRDby10years第68頁MPGNtypeII-clinicalfeaturesTypeIIanautoimmunediseasewithan