Glomerulonephritis in children

Glomerulonephritis in children

Pavlyshyn H.A.

Acute glomerulonephritis is the inflammation of the glomeruli which causes the kidneys to malfunction

• It is also called Acute Nephritis, Glomerulonephritis and Post-Streptococcal Glomerulonephritis

• Predominantly affects children from ages 2 to 12

• Incubation period is 2 to 3 weeks

Some progress as either focal segmental glomerulosclerosis ortubulointerstitial nephritis

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• Proteinuria – asymptomatic• Haematuria – asymptomatic• Hypertension• Nephrotic syndrome• Nephritic syndrome• Acute renal failure• Rapidly progressive renal failure• End stage renal failure

Presentation

• Hematuria with Proteinuriawith Dysmorphic rbcswith Rbc casts

• Oliguria

• Volume overload

• Hypertension

Liquid Renal Biopsy

Urine Sediment Analysis

G4 cell

Other H&P findings

• Neurological changes• Pharyngitis• URI / sinusitis• Hemoptysis• Rash• Murmur• Arthritis• Edema

Complement AbnormalitiesAb-Ag complexes

Classical pathway C3 convertase

Microbial surfaces(polysaccharides)

Alternative pathway C3 convertase

C3 C3b

C3a

(C4 + C2) (C4bC2a) Membrane attack complex

Recruitment of PMNs

Opsonization, phagocytosis

Anaphylaxis,Chemotaxis

Differential Diagnosis

Hypocomplementemia

• PIGN• MPGN• SLE• Cryoglobulinemia• Bacterial Endocarditis• Shunt nephritis

Normal complement

• HUS• IgAN• HSP• Alport’s / TBMD

-hemolytic Streptococci

• Most common organism in PIGN

• 20% children are asymptomatic carriers

• Nephritic factor

• Host susceptibility factors (HLA-DR)

• Treatment of prodromal illness doesn’t prevent nephritis

• ASO titers are NOT helpful

Post Infectious GN

Pathogenesis• Strep antigens trigger antibodies that cross-react to glomeruli • Circulating immune complexes get filtered by glomerulus & get

stuck• Immune complexes activate complement• Diffuse & generalized damage to glomeruli• ↓ GFR due to inflammation, damage to BM• ↓ RBF in proportion to GFR, so filtration fraction normal• Tubular function is preserved• Plasma renin and aldosterone are normal

Presentation• 7-14 days after pharyngitis• 14-21 days after impetigo (upto 6 wks)• Abrupt onset

Manifestations of PIGN

• Edema 85%• HTN 60-80%• Gross hematuria 25-33%• CNS (i.e. Sz) 10%• Nephrotic syndrome rare• ARF not uncommon• C3 decreased• C4 typically normal

Management of PIGN

• Antibiotics do NOT prevent GN• Sodium & Fluid restriction• Antihypertensives, diuretics for HTN• Dialysis if necessary• Prognosis usually excellent

0.5% mortality due to pulmonary edema or pneumonia<1% progress to CKD stage 5

• Follow-upGross hematuria resolves within 2 weeksComplement low for 6-8 weeksProteinuria remains upto 6 monthsHematuria remains upto 2 years

Renal Biopsy

Histopathology

Diffuse = all glomeruli

Generalized = all segments of glomeruli

IgG Immunofluorescence

Starry Sky Pattern

Electron microscopy - Normal

Foot processes

Basementmembrane

Electron microscopy of PIGN

• Subepithelial immune deposits (humps) Mesangial, subendothelial, intramembranous deposits less common

• Effacement of foot processes

Hemolytic Uremic Syndrome

• 2 cases/100,000 annually

• Peak incidence <5yo (6/100,000)

• More common June-September

• ClassificationD+ diarrhea associatedStrep pneumoAtypical HUS ADAM-TS13, C1q

def

Presentation of D+ HUS

• Prodromal acute gastroenteritis Shiga toxin producing E.coli O157:H7 Transmission from beef, veggies, direct person-to-person, and

contaminated water all reported Incubation period 3-4 days Bloody diarrhea 2-3 days after cramping begins 50% with emesis, afebrile or low grade fever only

• Hemolytic anemia• Thrombocytopenia• ARF

Begins 2-14 days after diarrhea

• CNS disease Overlap with ITP in 33% HUS cases Somnolence, confusion, seizures, coma

Microangiopathic Hemolytic Anemia

Henoch Schönlein Purupura

Henoch Schönlein Purupura

• GI tractCramping, vomiting, diarrhea

• Skin rashLower extremities, buttocks

• Joint involvement• HSP nephritis

Incidence 20-50%In 80%, occurs within 4 weeks of rash & GI upsetIn 15%, occurs upto 1-3 months after rash & GI

upset

Pathogenesis of Alport’s

• Abnormality of type IV collagen

• Disordered basement membrane

• Splitting of lamina densa of GBM

Crescentic GN

Type Serology Primary Secondary

I Anti-GBM+ ANCA- Anti-GBM disease Goodpasture’s

II Anti-GBM- ANCA- idiopathic SLE, IgAN, MPGN

III Anti-GBM- ANCA+ Microscopic polyangiitis,

Wegener’s

Drug-induced

IV Anti-GBM+ ANCA+ Anti-GBM disease Goodpasture’s

Vasculitides

C-ANCA P-ANCAAnti-proteinase 3 antibodies Anti-myeloperoxidase antibodies

75% sensitive for Wegener’s 66% sensitive for Microscopic polyangiitis

Anti-GBM Disease

Silver stain IgG immunofluorescence