IgA Nephropathy vs Post-Streptococcal GN: How to Tell Them Apart
Both IgA nephropathy and PSGN are immune complex–mediated glomerulonephritides that present with hematuria and RBC casts following an infection, making them classic look-alikes on exams. The single most decisive axis is the timing relative to the infection—synpharyngitic in IgA nephropathy versus a latent post-infectious interval in PSGN—reinforced by complement levels, which are normal in IgA and low in PSGN.
How to tell them apart
| Feature | IgA Nephropathy (Berger Disease) | Post-Streptococcal Glomerulonephritis (PSGN) |
|---|---|---|
| Timing of Hematuria | Synpharyngitic—gross hematuria appears during or within 1–2 days of the URI | Latent period—hematuria appears 1–3 weeks after pharyngitis or 3–6 weeks after skin infection |
| Preceding Infection | Mucosal (upper respiratory or GI) infection concurrent with hematuria | Group A strep pharyngitis or skin infection/impetigo preceding hematuria by a latent interval |
| Complement Profile | Normal C3 and C4 | Low C3 with normal C4 (alternative pathway activation); C3 normalizes by 6–8 weeks |
| Age Group | Young adults (20–30 years), male predominance | Children, peak age 6–10 years |
| Prognosis | Variable; 20–40% progress to ESRD over 20 years | Excellent in children (>95% full recovery) |
| Recurrence | Episodic gross hematuria recurring with each URI | Rare; usually a single, self-limited episode |
| Treatment | ACE-I/ARB for proteinuria control; steroids for severe/crescentic disease | Supportive care only (salt restriction, diuretics, antihypertensives) |
| Immunofluorescence | Mesangial IgA deposits (diagnostic), may also show IgG and C3 | "Starry sky" granular pattern with IgG and C3 |
| Electron microscopy | Mesangial deposits | Subepithelial "humps" |
The reasoning
Anchor on two features first: the temporal relationship of the hematuria to the infection and the complement profile. Hematuria that coincides with the sore throat (synpharyngitic) plus normal C3 and C4 nails IgA nephropathy, while hematuria that appears after a latent interval plus a low C3 with normal C4 (alternative pathway activation that consumes and then recovers) points to PSGN. The normal C4 in PSGN is a high-yield discriminator from classical-pathway diseases like lupus nephritis, which shows low C3 AND low C4. Age and clinical context add weight—a young adult with recurrent gross hematuria episodes suggests IgA, whereas a school-aged child with a single episode of cola-colored urine and periorbital edema suggests PSGN. When ambiguity persists, biopsy arbitrates: mesangial IgA deposits are diagnostic of IgA nephropathy, and subepithelial humps with a starry-sky IgG/C3 pattern confirm PSGN.
Key tests
- Serum complement: normal C3 and C4 in IgA nephropathy versus low C3 with normal C4 in PSGN, with C3 normalizing by 8 weeks—failure to normalize should prompt reconsideration of the diagnosis.
- Streptococcal serologies (ASO titer for pharyngitis, anti-DNase B for skin infection): elevated/positive in PSGN, not part of IgA nephropathy.
- Renal biopsy with immunofluorescence and electron microscopy: mesangial IgA deposits with mesangial proliferation in IgA nephropathy versus diffuse proliferative GN, "starry sky" IgG/C3, and subepithelial humps in PSGN.
- Urinalysis and history correlating the timing of hematuria to infection: hematuria concurrent with URI supports IgA nephropathy, whereas a 1–3 week (or 3–6 week for skin) delay supports PSGN.
What they share
- Nephritic presentation with hematuria, dysmorphic RBCs, and RBC casts confirming glomerular origin
- Both are triggered by antecedent infection (though the infection type and timing differ)
- Immune complex–mediated glomerular injury with C3 deposition seen on immunofluorescence
- Hypertension can occur in both
Pitfalls
- Assuming any post-URI hematuria is PSGN—the concurrent (synpharyngitic) timing and normal complement instead point to IgA nephropathy.
- Forgetting that C3 in PSGN should normalize by 8 weeks; persistently low complement should prompt consideration of an alternative diagnosis such as MPGN or lupus nephritis.
- Mislabeling PSGN complement consumption as classical pathway—PSGN activates the alternative pathway, giving low C3 with a normal C4, unlike lupus nephritis where both C3 and C4 fall.
- Overlooking that both conditions can show C3 on immunofluorescence—it is the presence of mesangial IgA versus subepithelial humps that distinguishes them.
- Confusing IgA nephropathy with IgA vasculitis (HSP), which has identical renal pathology but adds palpable purpura, arthritis, and abdominal pain in young children.
Practice this the way the exam tests it — on branching cases where your decisions shape the patient.