Acute Glomerulonephritis
Acute Glomerulonephritis
Acute Glomerulonephritis
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OUTLINE
Definition
Etiology
Pathology/pathogenesis
Riskfactors
ClinicalPresentation
Investigation
DifferentialDiagnosis
Management
Outcome/Prognosis
IndicationforRenalBiopsy
Summary
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DEFINITION
AcuteGlomerulonephritis(AGN)ischaracterizedby:
AbruptOnsetHematuria
Edema
Hypertension
OliguriaandRenalinsufficiency.
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ETIOLOGYNEPHRITICSYNDROME
PSGNfollowsinfectionofthethroatorskinby
certainnephritogenicstrainsofgroupA
hemolyticstreptococci.
Epidemicsofnephritishavebeendescribedin
associationwiththroat(serotypesM1,M4,
M25,M12)andskin(serotypeM49)infections.
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Glomerularinflammationandinjurydueto:
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PATHOLOGY
Glomeruliappearenlarged
Diffusemesangialcellproliferation
Polymorphonuclearleukocyteinfiltrationpresent
Crescentsandinterstitialinflammationinsevere
cases.
Immunofluorescencemicroscopyrevealsapatternof
lumpybumpydepositsofimmunoglobulinand
complementontheglomerularbasement
membraneandinthemesangium.
Electronmicroscopy,electrondensedeposits,or
humps,areobservedontheepithelialsideofthe
glomerularbasementmembrane
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Hypercellularglomeruluswith Granularbumpypatternof
proliferatingendothelialandmesangial immunedepositson
cells,andneutrophilinfiltration. immunofluorescence
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D
BS
Ep
P L
D
Electronmicrographinpoststreptococcalglomerulonephritisdemonstratingelectrondensedeposits(D)ontheepithelialcell
(Ep)sideoftheglomerularbasementmembrane.Apolymorphonuclearleukocyte(P)ispresentwithinthelumen(L)ofthe
capillary.BS,Bowmanspace;M,mesangium
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PATHOGENESIS
THEORIES
1. Trapping of circulating immune complexesin
glomeruli
2. Molecular mimicry between strep antigensand
renal antigens (glom tissue acts as autoantigen
reacts with circulating antibodies formedagainst
strepantigens)
3. In situ immune complex formation againstanti
strepantibodiesandglomeruli
4.Directcomplementactivation
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RISKFACTORS
Throatinfection:Winterorearlyspring
Pyoderma:latesummerorfall
Overallriskofinfection:15%,regardlessofsite
Riskofinfectionafterpyoderma:25%
Asymptomaticcarriers:20%,maythusoccurinabsenceof
prodrome
Peakincidenceinpreschoolchildren.ClinicallyapparentGN
occursin<2%ofchildreninfectedwithstrepinfection
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CLINICALMANIFESTATIONS
Abruptonset
Age412years,M>F
Latentperiod:Throatinfection:12weeks
Skininfection:36weeks
HEMATURIA
SmokybrownorColacolored
Glomerular:dysmorphicRBC,castsinfreshlyspunurine
PROTEINURIA
Mildtomoderatebutnephroticrangeisrare
OLIGURIA
Transient50%,Anuriarare
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EDEMA:85%
Mild:periorbitalorpedal
Severe:hypertension,pleuraleffusionorascites
Adolescents:morelikelyfaceandlegs
HYPERTENSION:in80%
Headache,Somnolence
Changesinmentalstatus
Anorexia,Nausea,Convulsions
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HYPERTENSIVEEMERGENCY:10%
BP>30%increasedforage&sex
Evidenceofencephalopathy
Heartfailureorpulmonaryedema
AZOTEMIA:varyingdegrees
CIRCULATORYCONGESTION:20%
Dyspnoea,Orthopnoea
Cough,Tachycardia,Galloprhythm
Basalcreps,CCF,Pulmonaryedema
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PSGN:ATYPICALPRESENTATION
Pulmonaryedema
Congestivecardiacfailure
Hypertensiveencephalopathy
Renalfailure
Nephroticsyndrome
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INVESTIGATIONS
URINE
DysmorphicorcrenatedRBCandRBCcasts
Moderateproteinuria;510%nephroticrange(Lastsfor
approximately5month)
Leukocyteorgranularorhyalinecasts
BLOOD
- Transientelevationofureaandcreatinine
- LowcomplementS.C3in>90%infirst2weeks(normalisesin68
weeks)
- SerumCH50iscommonlydepressed,C4ismostoftennormalor
mildlydepresedinPSGN.
- ASOtitreselevated15weeksafterinfectionin80%,fourfoldrise,
Returntonormalafterseveralmonths
- Thebestsingleantibodytitertodocumentcutaneousstreptococcal
infectionistheantideoxyribonucleaseBlevel
ChestXraymayshowpulmonarycongestion,cardiomegaly
Tubularfunctionispreserved,ormildlyreduced
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DIFFERENTIALDIAGNOSISOFACUTEGLOMERULONEPHRITIS
ClinicalfeaturesofAcuteGlomerulonephritis
NormalS.C3
DecreasedSerumcomplement(C3,CH50)
Systemicdiseases
Systemicdiseases
Polyarteritisnodosa,Hypersensitivityvasculitis,
Lupusnephritis(focal75%,diffuse90%)
HenochSchnleinpurpura
Subacutebacterialendocarditis(90%)
Goodpasturesyndrome
Shuntnephritis(90%)
Renaldiseases
Essentialmixedcryoglobulinemia(85%)
IgAnephropathy,RPGN
Visceralabscess,Renaldiseases
TypeI(antiGBMdisease)
AcutepostinfectiousGN(90%)
TypeII(immunecomplexCGN)
MembranoproliferativeGNTypeI(5080%)
TypeIII(pauciimmuneCGN)
PostinfectiousGN(nonstreptococcal)
Serologicevidenceofanantecedentstreptococcalinfection(ASO,antiDNaseB,streptozymetest)
Positiveand/orreturnoflowserumC3complement Negativeorfailureoflowserum
tonormalby68wk C3complementtoreturntonormalby68wk
Lupusnephritis(ANA+,AntidSDNAAb)
AcutepoststreptococcalGN Essentialmixedcryoglobulinemia(cryoglobulin,hepatitisCvirus)
Shuntnephritis,Visceralabscess(bloodculture)
MembranoproliferativeGN(C3NF)
Bacterialendocarditis,PostinfectiousGN(nonstreptococcal
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MANAGEMENTGENERAL
Saltrestricteddiet,lowK
Fluidintake(600ml/m2+previousdaysoutput)
Frusemideorloopdiureticsforpromptdiuresisin
fluidoverload,volumedependenthypertension,
cardiovascularcongestion
HypertensiveemergenciesAntihypertensives
Cachannelblockers
Loopdiuretics
ACEinhibitors
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MANAGEMENTSPECIFIC
Pulmonaryedema
Aggressivediuresis,Oxygen,Morphine,Ventilation
Hyperkalemia
Oral/ivRestriction,Kbindingresins
NebulisedSalbutamol,Glucoseinsulin
Calciuminfusion
Dialysis
Fluidoverload
Severeazotemia
Electrolyteabnormalities
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DAILYMONITORING
Clinical:Edema,JVP,BP
Fluidintakeandoutput
Weight
Respiratorystatus
Neurologicalstatus
ECGifhyperkalemic
Biochemical:Urinemicroscopy
BloodUrea,Creatinine
Electrolytes
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MOSTIMPORTANTINACUTENEPHRITIS
Clinicaldiagnosis
Antecedentstreptococcalinfection+
Serologicalmarkersofimmunemediatedinflammation
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RPGN
IfSuspected:
IsamedicalemergencycanprogressrapidlytoESR
Requireshistopathologicalconfirmation
Aggressiveimmunosuppressivetreatment
Optionsfortreatment:
Oralsteroids
ivMethylPrednisolone
ivCyclophosphamide
Plasmapheresis
Haemodialysis
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RPGNepithelialcellproliferationinsidetheBowmans
capsulecausingcrescentformationandcompressionof
underlyingglomerulartuft
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OUTCOMEPROGNOSIS
Usuallyselflimiting,goodprognosismortality<1%
Recoveryin710days
S.C3returnstonormalin68weeks
Hypertensionandhematuriamayresolveoverweeks
Proteinuriamaylastformonths
Microhematuriaforyears
RenalBiopsyrarelyneeded
ESRDoccurs<2%
Majorityhavelifelongprotection
Recurrentinfection:0.77%
LONGTERMFOLLOWADVOCTED
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INDICATIONSRENALBIOPSY
ATYPICALPRESENTATION
Nephroticrangeproteinuriainacutestage
Normalserumcomplement
ProgressivelyincreasingScreatinine
Prolongedhypocomplementemia>3m
Ongoingmacrohematuria
Longlastingproteinuria
Persistentazotemia
Associatedsymptomsofsystemicdisease
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INDICATIONSRENALBIOPSY
PostinfectiousGNandsecondarycauses
HepatitisBinfection
ShuntNephritis
Infectiveendocarditis
AssociatedwithHSP
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SUMMARY
Immunemediatedcondition
Mostcommonprototype:PSGN
SelflimitingrarelyprogressestoESRDorrecurs
Completerecoveryoccursin>95%ofchildren
Pathology governs treatment in atypical orsevere
cases.Outcomeisvariable
In secondary forms more specific treatmentmay
needed
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THANKYOU
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