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 Predominantly affects children from ages 2 to 12 Incubation period is 2 to 3 weeks

Autoimmune Reactions Some progress as either focal segmental glomerulosclerosis or tubulointerstitial nephritis 7

Possible Clinical Manifestations Proteinuria – asymptomatic Haematuria – asymptomatic Hypertension Nephrotic syndrome Nephritic syndrome Acute renal failure Rapidly progressive renal failure End stage renal failure 8

Presentation Hematuria Oliguria Volume overload Hypertension with Proteinuria with Dysmorphic rbcs with 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 Abnormalities Ab-Ag complexes Classical pathway C3 convertase Membrane attack complex Recruitment of PMNs Opsonization, phagocytosis Anaphylaxis, Chemotaxis (C4 + C2) (C4bC2a) C3 C3b C3a Microbial surfaces (polysaccharides) Alternative pathway C3 convertase

Differential Diagnosis Hypocomplementemia PIGN MPGN SLE Cryoglobulinemia Bacterial Endocarditis Shunt nephritis Normal complement HUS IgAN HSP Alport’s / TBMD

b-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 Presentation 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-up Gross hematuria resolves within 2 weeks Complement low for 6-8 weeks Proteinuria remains upto 6 months Hematuria remains upto 2 years

Renal Biopsy

Histopathology Diffuse = all glomeruli Generalized = all segments of glomeruli

IgG Immunofluorescence Starry Sky Pattern

Electron microscopy - Normal Basement membrane Foot processes

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 Classification D+ diarrhea associated Strep pneumo Atypical 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 tract Cramping, vomiting, diarrhea Skin rash Lower extremities, buttocks Joint involvement HSP nephritis Incidence 20-50% In 80%, occurs within 4 weeks of rash & GI upset In 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+

Vasculitides C-ANCA P-ANCA Anti-proteinase 3 antibodies Anti-myeloperoxidase antibodies 75% sensitive for Wegener’s 66% sensitive for Microscopic polyangiitis

Anti-GBM Disease Silver stain IgG immunofluorescence