glomerulonephritis in children
DESCRIPTION
Glomerulonephritis in children. Pavlyshyn H.A. Definition. 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 - PowerPoint PPT PresentationTRANSCRIPT
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