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Poststreptococcalglomerulonephritis

OfficialreprintfromUpToDate
www.uptodate.com2014UpToDate
Poststreptococcalglomerulonephritis
Author
PatrickNiaudet,MD

SectionEditor
FBruderStapleton,MD

DeputyEditor
MelanieSKim,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Nov2014.|Thistopiclastupdated:Jul18,2014.
INTRODUCTIONPoststreptococcalglomerulonephritis(PSGN)iscausedbypriorinfectionwithspecific
nephritogenicstrainsofgroupAbetahemolyticstreptococcus.TheclinicalpresentationofPSGNvaries
fromasymptomatic,microscopichematuriatothefullblownacutenephriticsyndrome,characterizedbyred
tobrownurine,proteinuria(whichcanreachthenephroticrange),edema,hypertension,andacutekidney
injury.Theprognosisisgenerallyfavorable,especiallyinchildren,butinsomecases,thelongterm
prognosisisnotbenign.
Theclinicalmanifestations,diagnosis,management,courseofdisease,andprognosisofPSGNwillbe
reviewedhere.
EPIDEMIOLOGYAlthoughPSGNcontinuestobethemostcommoncauseofacutenephritisinchildren
globally,itprimarilyoccursindevelopingcountries.Oftheestimated470,000newannualcasesofPSGN
worldwide,97percentoccurinregionsoftheworldwithpoorsocioeconomicstatus,withanannual
incidencethatrangesfrom9.5to28.5per100,000individuals[1,2].
Inmoredevelopedandindustrializedcountries,theincidencehasdecreasedoverthepastthreedecades
[24].BasedupondatafromtheItalianBiopsyregistry,theestimatedannualincidencewas0.3per100,000
individualsbetween1992and1994[5].TheriskofPSGNisincreasedinolderpatients(greaterthan60
yearsofage)andinchildrenbetween5and12yearsofage[5,6].PSGNisuncommoninchildrenlessthan
threeyearsofage.
PSGNcanpresentasasporadiccaseorduringanepidemicofgroupAstreptococcal(GAS)infection(ie,
skinandthroatinfections)[2].TheincidenceofclinicallydetectablePSGNinchildreninfectedduringaGAS
epidemicisabout5to10percentwithpharyngitisand25percentwithskininfections[7,8].
PATHOGENESISPoststreptococcalglomerulonephritis(PSGN)appearstobecausedbyglomerular
immunecomplexdiseaseinducedbyspecificnephritogenicstrainsofgroupAbetahemolyticstreptococcus
(GAS).Theresultingglomerularimmunecomplexdiseasetriggerscomplementactivationandinflammation.
(See"Mechanismsofimmuneinjuryoftheglomerulus"and"Overviewofthepathogenesisandcausesof
glomerulonephritisinchildren",sectionon'Pathogenesis'.)
ThefollowingareproposedmechanismsfortheimmunologicglomerularinjuryinducedbyGASinfection[9]:
Depositionofcirculatingimmunecomplexeswithstreptococcalantigeniccomponents
Insituimmunecomplexformationresultingfromdepositionofstreptococcalantigenswithinthe
glomerularbasementmembrane(GBM)andsubsequentantibodybinding
Insituglomerularimmunecomplexformationpromotedbyantibodiestostreptococcalantigensthat
crossreactwithglomerularcomponents(molecularmimicry)
Alterationofanormalrenalantigenthatelicitsautoimmunereactivity
Theavailableevidencesuggeststhatthemajorpathogeneticmechanismisinsituimmunecomplex
formationduetodepositionofstreptococcalnephritogenicantigenswithintheglomerulus[9].
NephritogenicantigensTherearetwoleadingcandidatesfortheputativestreptococcalantigen(s)
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responsibleforPSGN[9]:
Nephritisassociatedplasminreceptor(NAPlr),aglycolyticenzyme,whichhasglyceraldehyde3
phosphatedehydrogenase(GAPDH)activity
StreptococcalpyrogenicexotoxinB(SPEB),acationiccysteineproteinase
Resultsfromthefollowingstudiesprovidesupportfortheroleoftheseproteinsinthepathogenesisof
PSGN:
InastudyofJapanesepatientswithPSGN,NAPlrwaspresentinrenalbiopsysamplesobtainedwithin
thefirst14daysoftheirdisease[10].AntibodiestoNAPlrwerepresentintheseraof92percentof
patientswithPSGN,and60percentofpatientswithuncomplicatedgroupAstreptococcalinfections.
InanotherreportthatincludedpatientsfromLatinAmericaandSwitzerland,SPEBwasfoundin12of
17biopsies.SPEBdepositioncolocalizedwithcomplementdepositionandwithinthesubepithelial
electrondensedeposits(humps)thatarecharacteristicofPSGN(picture1)[11].AntibodiestoSPEB
weredetectedintheconvalescentserainall53patientswhoweretested.Incontrast,circulating
antibodiestoNAPlrwerefoundinonly5of47testedsera,andinonlyonebiopsysample.
AlthoughthefindingsfromthelaststudysupporttheroleofSPEBasthemorelikelynephritogenicantigen,
analternateexplanationisthatseparateantigensareresponsibleforPSGNindifferentpartsoftheworld
and/orinpatientswithvaryinggeneticbackgrounds[2,9].
Independentoftheimmuneresponse,bothSPEBandNAPlrcanactivatethealternatecomplement
pathway(acharacteristicfindinginPSGN)andenhancetheexpressionofadhesionmolecules.SPEBalso
canstimulatetheproductionofchemotacticcytokines[2].(See'Complement'below.)
PATHOLOGY
LightmicroscopyLightmicroscopyshowsadiffuseproliferativeglomerulonephritiswithprominent
endocapillaryproliferationandnumerousneutrophils(picture2andpicture3).Trichromestainmayshow
smallsubepithelialhumpshapeddeposits.Theseverityofinvolvementvariesandusuallycorrelateswiththe
clinicalfindings.Patientswhoareasymptomaticorhavemilddiseasemayhavebiopsiesthatshowlittle
glomerularinvolvement,whereaspatientswithdiffuseendocapillaryproliferativeglomerulonephritisare
morelikelytohavefullblownacutenephriticsyndrome(ie,redtobrownurine,proteinuria,edema,
hypertension,andacuterenalfailure).Crescentformationisuncommonandisassociatedwithapoor
prognosis.
ImmunofluorescencemicroscopyImmunofluorescence(IF)microscopyrevealsacharacteristicpattern
ofdepositsofimmunoglobulinG(IgG)andC3distributedinadiffusegranularpatternwithinthemesangium
andglomerularcapillarywalls(picture4)[12].Otherimmunereactants(eg,IgM,IgA,fibrin,andother
complementcomponents)mayalsobedetected.
ElectronmicroscopyThemostcharacteristicfeaturedetectedbyelectronmicroscopy(EM)arethe
domeshapedsubepithelialelectrondensedepositsthatarereferredtoashumps(picture1)[13].These
depositsalongwithsubendothelialdepositsareimmunecomplexesandcorrespondtothedepositsofIgG
andC3foundonIF[12].
Subendothelialimmunedepositsandsubsequentcomplementactivationareresponsibleforthelocal
influxofinflammatorycells,leadingtoaproliferativeglomerulonephritis,anactiveurinesediment,and
avariabledeclineinglomerularfiltrationrate[14].
Subepithelial"humps"areresponsibleforepithelialcelldamageandproteinuria,similartothatseenin
membranousnephropathy[15].(See"Causesanddiagnosisofmembranousnephropathy".)
IthasbeenproposedthattheclinicalcourseofPSGNisrelatedtothedifferentratesofclearanceofimmune
complexesatthesetwosites.(See'Correlationwithhistologicrecovery'below.)
CLINICALMANIFESTATIONSTheclinicalpresentationvariesfromasymptomatic,microscopic
hematuriatothefullblownacutenephriticsyndrome,characterizedbyredtobrownurine,proteinuria(which
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canreachthenephroticrange),edema,hypertension,andanelevationinserumcreatinine[1618].
However,mostchildrenareasymptomatic,asillustratedbyastudyof248childrenwithgroupAstreptococci
infection,ofwhom20developedurinaryabnormalitiesandatransientdecreaseinserumcomplement
activity,butonlyoneofwhomwasclinicallysymptomatic[17].
ThereisusuallyanantecedenthistoryofagroupAbetahemolyticstreptococcal(GAS)skinorthroat
infection[6,16,17].ThelatentperiodbetweenGASinfectionandpoststreptococcalglomerulonephritis
(PSGN)isdependentuponthesiteofinfection:betweenoneandthreeweeksfollowingGASpharyngitis
andbetweenthreeandsixweeksfollowingGASskininfection[19].
Thefollowingsymptomsarethemostcommonpresentingsignsinchildren[1618,20]:
EdemaGeneralizededemaispresentinabouttwothirdsofpatientsduetosodiumandwater
retention.Inseverecases,fluidoverloadleadstorespiratorydistressduetopulmonaryedema.
GrosshematuriaGrosshematuriaispresentinabout30to50percentofpatients.Theurinelooks
smoky,andteaorcocacolacolored.
HypertensionHypertensionispresentin50to90percentofpatientsandvariesfrommildtosevere.
Itisprimarilycausedbysaltandfluidretention.Hypertensiveencephalopathyisanuncommonbut
seriouscomplication.Resonancemagneticimagingmayshowposteriorreversible
leukoencephalopathy[21].Thesepatientsrequireemergentintervention.(See"Approachto
hypertensiveemergenciesandurgenciesinchildren",sectionon'Hypertensiveencephalopathy'and
"Managementofhypertensiveemergenciesandurgenciesinchildren".)
SubclinicalcasesofPSGNareprimarilycharacterizedbymicroscopichematuria[17,22,23].Such
patientswereoftendetectedduringepidemics.
PSGNisassociatedwithavariabledeclineinglomerularfiltrationratethatisdetectedbyariseinserum
creatinine.Acuterenalfailurerequiringdialysisisuncommon.(See"Acutekidneyinjuryinchildren:Clinical
features,etiology,evaluation,anddiagnosis".)
Laboratoryfindings
UrinalysisTheurinalysisinpatientswithPSGNrevealshematuria(someoftheredcellsaretypically
dysmorphic)withorwithoutredbloodcellcasts,varyingdegreesofproteinuria(picture5AC),andoften
pyuria.Nephroticrangeproteinuriaisuncommonandoccursinabout5percentofcasesatpresentation
[24].Theurinalysisshouldbeperformedonafreshlyvoidedspecimen.
ComplementInabout90percentofpatients,C3andCH50(totalcomplementactivity)are
significantlydepressedinthefirsttwoweeksofthediseasecourse[25,26].C4andC2levelsmaybelowin
somepatients,whichsuggestsactivationofbothclassicalandalternativepathways[27].TheC3andCH50
returntonormalwithinfourtoeightweeksafterpresentation.
ThecombinationofalowC3levelandanormaloronlyslightlydecreasedC4levelindicatesactivationof
thealternativepathwayofcomplement.Incontrast,lupusnephritisisassociatedwithactivationofthe
classicalpathwaywithreductionsinbothC3andC4.(See"Overviewandclinicalassessmentofthe
complementsystem",sectionon'Patternsassociatedwithactivationofspecificpathways'.)
CultureBecausePSGNpresentsweeksafteranantecedentGASinfection,onlyabout25percentof
patientswillhaveeitherapositivethroatorskinculture[6].Inpatientswithimpetigo,thereisanincreased
likelihoodofobtainingapositiveskinculture[16].
SerologyElevatedtitersofantibodiestoextracellularstreptococcalproductsisevidenceofarecent
GASinfection.(See"GroupAstreptococcus:Virulencefactorsandpathogenicmechanisms".)
Thestreptozymetest,whichmeasuresfivedifferentstreptococcalantibodies,ispositiveinmorethan95
percentofpatientsduetopharyngitisandabout80percentofthosewithskininfections[2830].Itincludes
thefollowingantibodies:
Antistreptolysin(ASO)
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Antihyaluronidase(AHase)
Antistreptokinase(ASKase)
Antinicotinamideadeninedinucleotidase(antiNAD)
AntiDNAseBantibodies

Theseantibodiescanalsobemeasuredindividually.Afterapharyngealinfection,theASO,antiDNAseB,
antiNAD,andAHasetitersarecommonlyelevated.Incomparison,onlytheantiDNAseBandAHasetiters
aretypicallyincreasedafteraskininfection.
IfonlytheASOtiterisusedtoscreenforGASinfection,itmaybefalselylowornegativeinpatientswithskin
infections[28].ItremainsausefultestinpatientswithPSGNduetoGASpharyngitisbutinsomecases,the
riseinASOtitermaybebluntedinpatientswithpharyngitiswhohavereceivedantimicrobialtherapy.(See
"GroupAstreptococcus:Virulencefactorsandpathogenicmechanisms".)
DIAGNOSISPoststreptococcalglomerulonephritis(PSGN)isusuallydiagnosedbaseduponclinical
findingsofacutenephritisanddemonstrationofarecentgroupAbetahemolyticstreptococcal(GAS)
infection.
Theclinicalfindingsofacutenephritisincludehematuriawithorwithoutredbloodcellcasts,variable
degreesofproteinuria,edema,andhypertension.(See'Clinicalmanifestations'above.)
DocumentationofarecentGASinfectionincludeseitherapositivethroatorskincultureorserologic
tests(eg,antistreptolysin[ASO]orstreptozymetest).(See'Serology'above.)
AlthoughalowC3and/orCH50(totalcomplement)levelareconsistentwithadiagnosisofPSGN,these
complementcomponentsmayalsobedecreasedinotherformsofglomerulonephritis,including
membranoproliferativeglomerulonephritis.(See'Differentialdiagnosis'below.)
AdelayinthediagnosisofPSGNismorecommoninchildrenwhodonothaveahistoryofanantecedent
GASinfectionandhavemicroscopichematuria.Thiswasillustratedinacaseseriesof57childrenwith
PSGNwhohadadelayindiagnosisofgreaterthan24hours[31].Inmostofthepatients,presenting
findingswereduetovolumeoverloadandincludedhypertension,edema,andpulmonaryedema.The
authorsconcludedthatacutenephritisneedstobeconsideredinanychildwhopresentswithsymptoms
secondarytovolumeoverloadandthataurinalysisshouldbeobtainedasaninitialdiagnostictest.
RenalbiopsyRenalbiopsyisnotperformedinmostpatientstoconfirmthediagnosisofPSGN,sincethe
resolutionofPSGNtypicallybeginswithinoneweekofpresentation.
Abiopsyisusuallyperformedinpatientsinwhomotherglomerulardisordersarebeingconsideredbecause
theydeviatefromthenaturalcourseofthePSGNortheypresentlatewithoutaclearhistoryofprior
streptococcalinfection.(See'Differentialdiagnosis'belowand'Course'below.)
PersistentlylowC3levelsbeyondsixweeksaresuggestiveofadiagnosisofmembranoproliferative
glomerulonephritis.
RecurrentepisodesofhematuriaaresuggestiveofIgAnephropathyandarerareinPSGN.
AprogressiveincreaseinserumcreatinineisuncharacteristicofPSGN,butthereareoccasional
patientswhodonotrecoverfromtheacuteepisode.(See'Course'below.)
DIFFERENTIALDIAGNOSISThediagnosisofPSGNisgenerallystraightforwardinpatientsoncethe
diagnosisofacutenephritisismade,thereisdocumentationofarecentgroupAbetahemolytic
streptococcal(GAS)infection,andthenephritisbeginstoresolvewithinoneortwoweeksofpresentation.
However,ifthereisprogressivediseasebeyondtwoweeks,persistenthematuriaorhypertensionbeyond
fourorsixweeks,orthereisnotadequatedocumentationofanantecedentGASinfection,thefollowing
causesofglomerulonephritis(GN)needtobeconsidered.Arenalbiopsymaybeneededtodifferentiate
PSGNfromtheseotherdisorders.
Membranoproliferativeglomerulonephritis(MPGN)ThepresentationofMPGNmaybe
indistinguishableinitiallyfromPSGN.Ittypicallypresentswithhematuria,hypertension,proteinuria,and
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hypocomplementemia,whichmayfollowanupperrespiratoryinfectioninsomepatients.However,
patientswithMPGNcontinuetohavepersistenturinaryabnormalitiesandhypocomplementemia
beyondfourtosixweeksandpossiblyafurtherelevationinserumcreatinine.Incontrast,patientswith
PSGNtypicallyhaveresolutionoftheirdiseaseandareturnofnormalC3andCH50levels.(See
"Clinicalpresentation,classification,andcausesofmembranoproliferativeglomerulonephritis".)
IgAnephropathyPatientswithIgAnephropathyoftenpresentafteranupperrespiratoryinfection,
similartothepresentationofpatientswithPSGN.PotentialdistinguishingfeaturesfromPSGNinclude
ashortertimebetweentheantecedentillnessandhematuria(lessthan5versusmorethan10daysin
PSGN)andahistoryofpriorepisodesofgrosshematuriasincerecurrenceisrareinPSGN.(See
"Differentialdiagnosisandevaluationofglomerulardisease",sectionon'Hematuriafollowingupper
respiratoryinfection'and"ClinicalpresentationanddiagnosisofIgAnephropathy".)
SecondarycausesofglomerulonephritisLupusnephritisandHenochSchnleinpurpura(IgA
vasculitis)nephritissharesimilarfeaturestoPSGN.However,extrarenalmanifestationsofthe
underlyingsystemicdiseasesandlaboratorytestingshoulddifferentiatethemfromPSGN.
Measurementofserumcomplementmayalsobehelpful.Hypocomplementemiaisnotobservedin
patientswithHenochSchnleinpurpura(IgAvasculitis)andthehypocomplementemiathatoccursin
lupusnephritisis,asmentionedabove,associatedwithreductionsinbothC3andC4,whereasC4
levelsareusuallynormalinPSGN.(See"RenalmanifestationsofHenochSchnleinpurpura(IgA
vasculitis)"and"Diagnosisandclassificationofrenaldiseaseinsystemiclupuserythematosus"and
'Complement'above.)
BothhepatitisBandendocarditisassociatedglomerulonephritissharecommonfeatureswithPSGN
andalsowillpresentwithreductionsinC3andC4.(See"RenaldiseaseassociatedwithhepatitisB
virusinfection"and"Renaldiseaseinthesettingofinfectiveendocarditisoraninfectedventriculoatrial
shunt".)
PostinfectiousGNduetoothermicrobialagentsAcutenephritisduetoviralandotherbacterial
agentshasbeenreported(table1).TheirclinicalpresentationissimilartothatofPSGNexceptthat
thereisnodocumentationofanantecedentGASinfection.
MANAGEMENTThereisnospecifictherapyforpoststreptococcalglomerulonephritis(PSGN).Thereis
noevidencethataggressiveimmunosuppressivetherapyhasabeneficialeffectinpatientswithrapidly
progressivecrescenticdisease[32].However,patientswithmorethan30percentcrescentsonrenalbiopsy
areoftentreatedwithmethylprednisolonepulses.(See"Overviewoftheclassificationandtreatmentof
rapidlyprogressive(crescentic)glomerulonephritis",sectionon'Treatment'.)
Managementissupportiveandisfocusedontreatingtheclinicalmanifestationsofthedisease,particularly
complicationsduetovolumeoverload.Theseincludehypertensionand,lesscommonly,pulmonaryedema.
Generalmeasuresincludesodiumandwaterrestrictionandloopdiuretics.(See"Evaluationand
managementofedemainchildren",sectionon'Generaltreatmentapproach'.)
Loopdiureticsgenerallyprovideapromptdiuresiswithreductionofbloodpressureandedema.Inour
practice,intravenousfurosemideisgivenataninitialdoseof1mg/kg(maximum40mg).
Infrequently,patientshavehypertensiveencephalopathyduetoseverehypertension.Thesepatientsshould
betreatedemergentlytoreducetheirbloodpressure.Oralnifedipineorparenteralnicardipineareeffective,
whileangiotensinconvertingenzymeinhibitorsshouldbeusedwithcautionduetotheriskofhyperkalemia.
(See"Managementofhypertensiveemergenciesandurgenciesinchildren",sectionon'Approach'.)
PatientswithPSGNhavevariablereductionsinrenalfunction,andsomepatientsrequiredialysisduringthe
acuteepisode.Themanagementofacutekidneyinjuryinchildren,includingindicationsfordialysis,is
discussedseparately.(See"Preventionandmanagementofacutekidneyinjury(acuterenalfailure)in
children",sectionon'Managementofacutekidneyinjury(AKI)'.)
PatientswithevidenceofpersistentgroupAstreptococcalinfectionshouldbegivenacourseofantibiotic
therapy.(See"Treatmentandpreventionofstreptococcaltonsillopharyngitis"and"Impetigo",sectionon
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'Treatment'.)
COURSEResolutionoftheclinicalmanifestationsofPSGNisgenerallyquiterapid,assumingconcurrent
resolutionoftheinfection.Adiuresistypicallybeginswithinoneweek,andtheserumcreatininereturnsto
thepreviousbaselinebythreetofourweeks[18,33].
Theurinaryabnormalitiesdisappearatdifferingrates.Hematuriausuallyresolveswithinthreetosixmonths.
Proteinuriaalsofallsduringrecovery,butatamuchslowerrate.Amildincreaseinproteinexcretionisstill
presentin15percentat3years,and2percentat7to10years[34].
Inseverecaseswithnephroticrangeproteinuria,thisdegreeofproteinuriamaypersistforsixmonthsor
more,longafterthehematuriahasdisappeared[35,36].Patientsfirstseenatthislatestageareoften
thoughttohaveoneofthecausesoftheidiopathicnephroticsyndrome(eg,membranousnephropathy,focal
segmentalglomerulosclerosis,orminimalchangedisease).
CorrelationwithhistologicrecoveryThehistologiccourseparallelstheimprovementsseenclinically.
Thereisamarkedreductioninthenumberofinflammatorycellsintheglomeruliandthenumberofimmune
depositsseenonelectronmicroscopyastheclinicalmanifestationsresolve[15,37].
Theprolongedresolutionofproteinuriacomparedwiththemorerapidreturnofrenalfunctionandremission
ofhematuriaprobablyreflectstheslowerrateofclearanceofsubepithelialcomparedwithsubendothelial
immunecomplexes.
Subendothelialimmunecomplexesarerapidlyclearedbytheinflammatorycellsfromthesystemic
circulation,therebyaccountingfortheresolutionofhematuriaandrenalinsufficiency[15].Theymay
notbeseenonrenalbiopsyunlessperformedearlyinthecourse.
Subepithelialdepositsareseparatedfromcirculatinginflammatorycellsbytheglomerularbasement
membrane,therebylimitingtheirrateofremoval[15,37].Ingeneral,thedegreeofproteinuriacorrelates
withthenumberofsubepithelialdeposits[35].
RecurrenceRecurrentepisodesofPSGNarerare[16].Thismaybeduetothelongtermpersistenceof
antibodiestonephritisassociatedstreptococcalantigens[38].(See'Nephritogenicantigens'above.)
PROGNOSISMostpatients,particularlychildren,haveanexcellentoutcome[2,14,18,34].Thisistrue
eveninpatientswhopresentwithacuterenalfailureandmayhavecrescentsontheinitialrenalbiopsy
[32,33,39].Areviewofthreecaseseriesof229childrenwithpoststreptococcalglomerulonephritis(PSGN)
foundthatapproximately20percenthadanabnormalurinalysis(proteinuriaand/orhematuria),butalmost
all(92to99percent)hadnormaloronlymodestlyreducedrenalfunction5to18yearsafterpresentation[2].
However,thelongtermprognosisofPSGNisnotalwaysbenign[40].Somepatients,particularlyadults,
develophypertension,recurrentproteinuria(witharelativelynormalurinesediment),andrenalinsufficiency
aslongas10to40yearsaftertheinitialillness[4144].AstudyfromAustraliainvolving200Aboriginal
childrenwhohadhadatleastoneepisodeofPSGN,with27havinghadmultipleepisodes,foundthatfive
yearsormorelater,thesepatientswerethreetofourtimesmorelikelytohavesignificantalbuminuria
comparedwithpeoplewithoutaprevioushistoryofPSGN[45].
Theselaterenalcomplicationsareassociatedwithglomerulosclerosisonrenalbiopsy,whichisthoughtto
behemodynamicallymediated.Accordingtothishypothesis,someglomeruliareirreversiblydamaged
duringtheacuteepisodeandcompensatoryhyperfiltrationintheremainingglomerulimaintainsarelatively
normalglomerularfiltrationrate.However,thisadaptiveresponseresultsinincreasesinglomerularpressure
andsize,bothofwhichmaythencontributetononimmunologicglomerularinjuryandprogressiverenal
dysfunction.Itispossiblethat,inthosepatientswhodevelopglomerulosclerosis,renaldamagecanbe
preventedoramelioratedbyantihypertensivetherapy(preferentiallywithanangiotensinconvertingenzyme
inhibitor).(See"Secondaryfactorsandprogressionofchronickidneydisease".)
AnalternateexplanationforthelatedevelopmentofrenalfailureinpatientsdiagnosedinitiallywithPSGNis
thatsomepatientsmayactuallyhavemembranoproliferativeglomerulonephritis[14].(See'Differential
diagnosis'above.)
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SUMMARYANDRECOMMENDATIONS
Poststreptococcalglomerularnephritis(PSGN)isthemostcommoncauseofacutenephritis
worldwide.Itprimarilyoccursinthedevelopingworld.TheriskofPSGNisgreatestinchildrenbetween
5and12yearsofage,andinolderadultsgreaterthan60yearsofage.(See'Epidemiology'above.)
PSGNiscausedbyglomerularimmunecomplexdiseaseinducedbyspecificnephritogenicstrainsof
groupAbetahemolyticstreptococcus(GAS).Thetwoleadingcandidatenephritogenicantigensare
nephritisassociatedplasminreceptorandstreptococcalpyrogenicexotoxinB.(See'Pathogenesis'
above.)
ThecharacteristicpathologicfeaturesofPSGNaredemonstratedbyelectronmicroscopy(dome
shapedsubepithelialdeposits)(picture4)andimmunofluorescence(depositionofIgGandC3ina
diffusegranularpatterninthemesangiumandglomerularcapillarywalls)(picture3).Thelight
microscopicfindingsofcellularinfiltrationandglomerularproliferationarenonspecific.(See'Pathology'
above.)
Although,themostcommonclinicalfindingsincludeedema,grosshematuria,andhypertension,the
presentationofPSGNvariesfromasymptomatic,microscopichematuriatothefullblownacute
nephriticsyndrome(grosshematuria,proteinuria,edema,hypertension,andacutekidneyinjury).(See
'Clinicalmanifestations'above.)
Laboratoryfindingsincludeanabnormalurinalysis(dysmorphicredbloodcells,varyingdegreesof
proteinuria,redbloodcellcasts,andpyuria),positiveserologyforantibodiestostreptococcalantigens,
andhypocomplementemia.(See'Laboratoryfindings'above.)
PSGNistypicallydiagnosedbaseduponthefindingsofacutenephritisanddemonstrationofarecent
GASinfection.(See'Diagnosis'above.)
Althoughseveralglomerulonephritides(eg,membranoproliferativeglomerulonephritisandIgA
nephropathy)havesimilarpresentationstoPSGN,specificclinicaldifferencesusuallycandifferentiate
amongthem.Incaseswherethediagnosisisuncertain,arenalbiopsymaybeneededtoidentifythe
specificrenaldisease.(See'Differentialdiagnosis'aboveand'Renalbiopsy'above.)
ThereisnospecifictherapytotreatPSGN.Managementissupportiveandisfocusedupontreatingthe
volumeoverloadthatcausestheclinicalcomplicationsofPSGN.Thesegeneralmeasuresinclude
sodiumandwaterrestriction,anddiuretictherapy.
Inpatientswithacuterenalfailure,dialysismayberequired.Theindicationsfordialysisare
discussedseparately.(See"Preventionandmanagementofacutekidneyinjury(acuterenal
failure)inchildren",sectionon'Managementofacutekidneyinjury(AKI)'.)
Inpatientswithhypertension,wesuggestadministrationoflasixtoprovideapromptdiuresisand
areductionofbloodpressure(Grade2C).Infrequently,patientsmayhavehypertensive
encephalopathyduetoseverehypertensionandrequireemergenttherapytoreducetheirblood
pressure.(See'Management'aboveand"Managementofhypertensiveemergenciesand
urgenciesinchildren",sectionon'Approach'.)
Mostpatients,particularlychildren,havecompleteclinicalrecovery,andresolutionoftheirdisease
processbeginswithinthefirsttwoweeks.However,thereisasmallsubsetofpatientswhohavelate
renalcomplications(ie,hypertension,increasingproteinuria,andrenalinsufficiency).(See'Course'
aboveand'Prognosis'above.)
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27. WyattRJ,ForristalJ,WestCD,etal.Complementprofilesinacutepoststreptococcal
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42. PintoSW,SessoR,VasconcelosE,etal.Followupofpatientswithepidemicpoststreptococcal
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GRAPHICS
Electronmicrographofpostinfectious
glomerulonephritis

Electronmicrographshowssubepithelialdeposits(D)withasemilunar,
humpshapedappearanceinpostinfectiousglomerulonephritis.The
humpssitontopoftheglomerularbasementmembrane(GBM).A
neutrophilisattachedtothedenudedGBM,contributingtothe
glomerularinflammation.Neutrophilattractionrequirestheinitial
presenceofsubepithelialimmunedepositssothatcomplement
chemoattractantshaveaccesstothesystemiccirculation.
CourtesyofHelmutRennke,MD.
Graphic76739Version4.0

Electronmicrographofanormalglomerulus

Electronmicrographofanormalglomerularcapillaryloopshowing
thefenestratedendothelialcell(Endo),theglomerularbasement
membrane(GBM),andtheepithelialcellswithitsinterdigitatingfoot
processes(arrow).TheGBMisthin,andnoelectrondensedeposits
arepresent.Twonormalplateletsareseeninthecapillarylumen.

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CourtesyofHelmutRennke,MD.
Graphic50018Version6.0

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Postinfectiousglomerulonephritis

Lowpowerlightmicrographshowingdiffuse,proliferative
glomerulonephritisasmaybeseeninpostinfectiousglomerulonephritis.
Theglomeruliaresohypercellular(arrows)thatopencapillarylumens
cannotbeseen,andtheglomerulimaybehardtodistinguishfromthe
surroundinginterstitium.
CourtesyofHelmutRennke,MD.
Graphic80304Version2.0

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PoststrepGNhighpower

Acutepostinfectiousglomerulonephritis.Theglomerulishowglobal
intracapillaryhypercellularitywithlargenumbersofpolymorphonuclear
leukocytesintheglomerularcapillarylumina(hematoxylinandeosin
stain,x400).
CourtesyofPeterDegrell,UniversityofPcsFacultyofMedicine,
NephrologicalCenter,Pcs,Hungary.
Reproducedwithpermissionfrom:KnoersNV,MonnensLA.Nephrogenic
diabetesinsipidus.In:PediatricNephrology,5thed,AvnerED,HarmonWE,
NiaudetP(Eds),LippincottWilliams&Wilkins,Philadelphia2004.Copyright
2004NineV.A.M.Knoers.
Graphic51022Version2.0

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Postinfectiousglomerulonephritis

Immunofluorescencemicroscopyshowsgranulardepositionof
complementintheglomerulartuftinpostinfectiousglomerulonephritis.
IgGcanalsobeseeninthesamedistribution.
CourtesyofHelmutRennke,MD.
Graphic56846Version1.0

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Phasecontrastmicrographshowingdysmorphic
redcellsinurinesediment

Phasecontrastmicroscopyshowingdysmorphicredcellsinapatient
withglomerularbleeding.Acanthocytescanberecognizedasringforms
withvesicleshapedprotrusions(arrows).
CourtesyofHansKhler,MD.
Graphic79440Version3.0

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Scanningelectronmicrographshowingdysmorphic
redcellsinurinesediment

Scanningmicroscopyshowingdysmorphicredcellsinapatientwith
glomerularbleeding.Acanthocytescanberecognizedasringformswith
vesicleshapedprotrusions(arrows).
CourtesyofHansKhler,MD.
Graphic62064Version3.0

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Photomicrographofurinesedimentwitharedcell
cast

Urinesedimentshowingfreeredcellsandaredcellcastthatistightly
packedwithredcells.Itismorecommonforredcellcaststohave
fewerredcellstrappedwithinahyalineorgranularcast.Redcellcasts
arevirtuallydiagnosticofglomerulonephritisorvasculitis.
CourtesyofHarvardMedicalSchool.
Graphic55778Version3.0

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Bacterialandviralagentsassociatedwithpostinfectious
glomerulonephritis
Bacterialinfections
Skinorthroat(StreptococcusgroupA)
Endocarditis(Staphylococcusaureus,Streptococcusviridans)
Visceralabcess(Staphylococcusaureus,E.coli,Pseudomonas,Proteusmirabilis)
Shuntnephritis(Staphylococcusaureus,Staphylococcusalbus,Streptococcusviridans)
Pneumonia(Diplococcuspneumoniae,Mycoplasma)
Typhoidfever(Salmonellatyphi)

Viralinfections
EpsteinBarrvirus
ParvovirusB19
Varicella
Cytomegalovirusinfection
Coxsackie
Rubella
Mumps
HepatitisB

Parasiticinfections
Schistosomamansoni
Plasmodiumfalciparum
Toxoplasmagondii
Filaria
Originalfiguremodifiedforthispublication.Reproducedwithpermissionfrom:NiaudetP.Nephritic
Syndrome.In:ComprehensivePediatricNephrology,GearyDF,SchaeferF(Eds),Mosby,
Philadelphia2008.IllustrationusedwiththepermissionofElsevierInc.Allrightsreserved.
Graphic76710Version3.0

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Disclosures
Disclosures:PatrickNiaudet,MDNothingtodisclose.FBruderStapleton,MDNothingto
disclose.MelanieSKim,MDEmployeeofUpToDate,Inc.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,these
areaddressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsfor
referencestobeprovidedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofall
authorsandmustconformtoUpToDatestandardsofevidence.
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