ACUTEGLOMERULONEPHRITIS

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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:

Acute, self limiting, reversible conditions(Acute

GlomerulonephritisorAGN):
Postinfectious AGN : can occur afterstreptococcal
(most common) or other bacterial infection/ viralor
Mycoplasmainfection
HenochSchnoleinNephritis
Firstpresentationofchronicdisease:
IgAnephropathy
Membranoproliferativeglomerulonephritis(MPGN)
SLE,PAN,WGandotherchronicvasculitis
AlportsSyndrome

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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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