Describe acute post-streptococcal glomerulonephritis with its pathogenesis and morphology.

Definition

• Chiefly affects children aged 6 to 10; still common in India
• Follows pharyngitis (1–2 weeks) or skin infection such as impetigo (3–6 weeks) — unlike rheumatic fever, which follows pharyngeal infection only
• Nephritogenic strains — M types 12 (throat) and 49 (skin)

Pathogenesis

Streptococcal infection with a nephritogenic strain → Antibody forms against streptococcal antigens (SPE B, nephritis-associated plasmin receptor) → immune complexes form — deposited from the circulation, or formed in situ against antigen planted in the glomerulus → Deposits lie subepithelially as characteristic "humps" → complement activation — serum C3 falls → Neutrophil and monocyte infiltration; endocapillary proliferation → Reduced filtration surface → oliguria, fluid retention, hypertension; capillary wall damage → haematuria

Morphology

• Where the deposits sit predicts the syndrome.
• subepithelial deposits in post-streptococcal disease are separated from the circulation by the basement membrane, so few inflammatory cells reach them — yet the humps are large and complement-activating, giving a nephritic picture.
• subendothelial deposits sit directly in contact with blood and provoke intense inflammation. Small, quiet subepithelial deposits without inflammation give membranous nephropathy and a nephrotic picture.

Clinical Features and Investigation

• Abrupt nephritic syndrome — "COCA-cola" or smoky urine, periorbital oedema on waking, hypertension, oliguria, malaise and headache
• Urine — dysmorphic red cells, red cell casts, mild proteinuria (usually under 3.5 g a day)
• Serum C3 is low and returns to normal within 6 to 8 weeks — a persistently low C3 suggests another diagnosis such as membranoproliferative glomerulonephritis or lupus
• Evidence of preceding streptococcal infection — raised ASO titre (better after throat infection) or anti-DNase B (better after skin infection); throat swab is often negative by presentation
• Renal biopsy is rarely needed in a typical child, and is reserved for atypical or non-resolving cases

Applied Aspects

• Prognosis in children is excellent — over 95% recover completely with supportive treatment alone: salt and fluid restriction, diuretics and antihypertensives
• Adults do less well, with a significant minority progressing to chronic kidney disease
• Antibiotics do not alter the course of established nephritis, but are given to eradicate the organism and limit spread to contacts
• Haematuria may persist microscopically for months and proteinuria for weeks; this is expected and does not by itself indicate progression
• Unlike rheumatic fever, there is NO recurrence and no need for prophylaxis — a contrast worth stating, since both follow the same organism
• Treating the sore throat does not reliably prevent nephritis, unlike rheumatic fever — another instructive difference between the two post-streptococcal diseases