NephrologyTier 1Disease (DEADMAN)

Post-streptococcal glomerulonephritis

Description

Immune-complex nephritic syndrome after an extrarenal streptococcal infection - not during it
Nephritogenic strains of *group A beta-haemolytic Streptococcus pyogenes***
- Pharyngitis: M types 1, 4, 12
- Impetigo/pyoderma: M types 2, 49, 55, 57, 60
The latent period is the diagnosis - it distinguishes PSGN from IgA nephropathy

Broader term post-infectious GN now preferred - staphylococcal (esp. MRSA) disease in diabetic and elderly adults is increasingly the dominant form in developed countries

Children 2-12 yrs; M:F ~2:1
Rare in developed urban settings; remains common in Aboriginal and Torres Strait Islander communities in remote Australia - alongside acute rheumatic fever and scabies-associated pyoderma
- A recognised contributor to the excess CKD burden in these communities
Global burden ~470,000 cases/yr, mostly in children in low-resource settings
In adults, post-infectious GN is now more often staphylococcal, in diabetics and the elderly - and it does much worse

Nephritogenic streptococcal antigens - NAPlr (nephritis-associated plasmin receptor) and SPeB (streptococcal pyrogenic exotoxin B)
- Planted in the glomerulus -> in-situ immune complex formation, plus deposition of circulating complexes
- -> alternative complement pathway activation
Low C3 with normal or near-normal C4 - the alternative pathway signature
- If C3 stays low beyond 12 weeks, the diagnosis is wrong - think C3 glomerulopathy or MPGN**
Endocapillary proliferation - neutrophil and monocyte infiltration -> nephritic syndrome (Na retention, oedema, HTN, haematuria)

Clinical - the nephritic syndrome

Latency: ~10-14 days after pharyngitis, ~21 days after skin infection (pyoderma), 2-4 weeks after other infections
Macroscopic haematuria - 'cola' or 'smoky' urine
Oedema (periorbital, on waking), hypertension, oliguria
Sub-nephrotic proteinuria usually; nephrotic-range in ~5-10% and predicts worse outcome
Malaise, loin ache, headache

Investigations

Urine: dysmorphic RBCs, RBC casts, proteinuria
Low C3 (and CH50); C4 normal or mildly low
- *C3 must normalise by 8-12 weeks* - persistent hypocomplementaemia mandates biopsy
Evidence of preceding streptococcal infection (throat swab often already negative)
- ASOT - rises after pharyngitis, poor after skin infection
- Anti-DNase B - the better test after pyoderma
- Streptozyme (multiple antibodies) most sensitive
Creatinine, UEC, FBE, albumin

Biopsy - only if atypical

Histology
- LM: diffuse endocapillary proliferation with neutrophils ('exudative')
- IF: granular IgG and C3 in a 'starry sky' or garland pattern
- EM: subepithelial 'humps' (large, dome-shaped deposits) with mesangial and subendothelial deposits too
Biopsy if: no latent period, C3 still low at >12 weeks, nephrotic-range proteinuria, rising creatinine or RPGN, age >50, systemic features, normal complement

Differential of low C3 nephritis

Low C3 + low C4: SLE, cryoglobulinaemia, shunt nephritis, endocarditis
Low C3 + normal C4: PSGN, C3 glomerulopathy (C3GN, dense deposit disease)

Supportive - and that is nearly all of it

Sodium and fluid restriction
Loop diuretic - treats both the oedema and most of the hypertension (volume-dependent)
Antihypertensives if needed - CCB or ACEi/ARB (watch K+ in AKI)
Dialysis rarely required

Antibiotics

Penicillin (or a macrolide if allergic) if there is ongoing streptococcal infection or in an outbreak/household contact setting
*Antibiotics do NOT alter the course of established nephritis* - the immune complexes are already deposited
Unlike acute rheumatic fever, PSGN is not prevented by treating the sore throat and does not warrant long-term prophylaxis

Immunosuppression

In staphylococcal (IgA-dominant) post-infectious GN

Treat the infection - the nephritis follows the source (endocarditis, osteomyelitis, deep abscess, infected line or prosthesis)
*Immunosuppression is harmful if the infection is not controlled*

Public health

Treat scabies and skin sores in remote Aboriginal and Torres Strait Islander communities - the modifiable upstream cause
Household contact screening in outbreaks

Group A streptococcal pharyngitis and pyoderma/impetigo; scabies
Overcrowding, remote Aboriginal and Torres Strait Islander communities, low-resource settings
Acute rheumatic fever - the other post-streptococcal sequela; the two rarely coexist and follow different nephritogenic/rheumatogenic strains
Staphylococcal (including MRSA) infection - IgA-dominant post-infectious GN in diabetes and the elderly
Infective endocarditis, ventriculoatrial shunt nephritis, deep abscess, osteomyelitis
Hepatitis B/C, HIV, syphilis, parasitic infection - other infection-related GN
C3 glomerulopathy - the key mimic when C3 stays low

The recovery sequence - in order

Renal function improves by ~4 weeks
C3 normalises by 8-12 weeks
Macroscopic haematuria clears within days-weeks; microscopic haematuria can persist 1-2 years
Proteinuria resolves last - up to 2 years
So persisting microhaematuria alone at 6 months is not failure; persisting low C3 is

Poorer outcome

~10-15% progress to ESKD across all ages (driven by the adult and staphylococcal cases)
Adults do much worse than children: persistent renal impairment in up to 30-50%
Predictors: adult onset, diabetes, nephrotic-range proteinuria, crescents on biopsy, persistent hypertension, staphylococcal aetiology

Complications

Hypertensive encephalopathy and seizures (children), pulmonary oedema, AKI
RPGN with crescents - rare, poor prognosis
Long-term hypertension and CKD - follow BP and urinalysis annually after an episode
Recurrence is rare - immunity to the nephritogenic M type

6 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.