A 6-year-old boy from rural India presents with acute nephritic syndrome (haematuria, hypertension, oedema, RBC casts) 2 weeks after pharyngitis. Serum C3 is low, and renal biopsy shows endocapillary proliferation with subepithelial humps. A 35-year-old man with a 10-year history of haematuria and proteinuria (2 g/day) presents with nephritic features and progressive renal insufficiency. Renal biopsy shows IgA deposits on immunofluorescence. Which finding best distinguishes IgA nephropathy from post-streptococcal GN?

Explanation

## Distinguishing IgA Nephropathy from PSGN ### Immunofluorescence Pattern: The Gold Standard Discriminator **Key Point:** The immunofluorescence (IF) pattern is the single most reliable discriminator. PSGN shows dominant C3 deposition (with minimal or no immunoglobulin), whereas IgA nephropathy shows **predominant IgA deposits with C3 co-deposition**. ### Comparison Table | Feature | IgA Nephropathy | PSGN | | --- | --- | --- | | **Immunofluorescence** | **Dominant IgA** (with IgG, IgM, C3) | **Dominant C3** (minimal Ig) | | **Serum C3** | Normal | Low (90% of cases) | | **Electron microscopy** | IgA-containing immune complexes in mesangium | Subepithelial "humps" (electron-dense) | | **Light microscopy** | Mesangial proliferation (IgA-dominant) | Endocapillary proliferation | | **Clinical course** | Chronic, progressive (50% ESRD in 20 years) | Acute, self-limited (90% recovery) | | **Age of onset** | Young adults (20–40 years) | Children (5–12 years) | | **Proteinuria** | Often >2 g/day at presentation | Usually <1 g/day | ### Why Immunofluorescence Is Pathognomonic **High-Yield:** IgA nephropathy is defined by **IgA-dominant** immunofluorescence. PSGN is defined by **C3-dominant** immunofluorescence with minimal or absent immunoglobulin staining. This distinction is diagnostic and cannot be inferred from clinical features alone. **Clinical Pearl:** The difference reflects the pathogenic mechanism: IgA nephropathy involves IgA1-dominant immune complexes (mucosal origin); PSGN involves circulating immune complexes with streptococcal antigen and complement activation via the classical pathway (hence C3 dominance). ### Why Other Features Are NOT Discriminators **Mnemonic:** **C3 vs IgA = Complement vs Immunoglobulin** - **Low C3 (Option A):** Present in ~90% of PSGN but normal in IgA nephropathy. However, absence of low C3 does not exclude PSGN, and IgA nephropathy can rarely show C3 deposition. IF pattern is more specific. - **Subepithelial humps (Option B):** Characteristic of PSGN but not pathognomonic; other post-infectious GN can show similar EM findings. - **Endocapillary proliferation (Option D):** Seen in both PSGN (endocapillary) and IgA nephropathy (mesangial, but can have endocapillary component). Light microscopy alone does not distinguish them.