A 35-year-old woman from rural India presents with progressive hematuria and proteinuria over 6 months. Serum creatinine is 2.1 mg/dL. Kidney biopsy shows IgA-dominant immunofluorescence with mesangial proliferation. What is the most common primary glomerulonephritis in the Indian subcontinent and Asia overall?

Explanation

## Most Common Primary Glomerulonephritis in Asia and India **Key Point:** IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with particularly high prevalence in Asia (especially East Asia, Southeast Asia, and the Indian subcontinent) and the Mediterranean region. It accounts for 20–50% of all primary GN cases depending on geographic region. ### Epidemiology and Geographic Variation | Region | IgA Prevalence | Most Common Cause of Acute GN | | --- | --- | --- | | **East Asia (Japan, China, Korea)** | 40–50% | IgA nephropathy | | **Southeast Asia & India** | 20–40% | IgA nephropathy (or PSGN in endemic areas) | | **Mediterranean** | 20–30% | IgA nephropathy | | **North America/Europe** | 10–15% | IgA nephropathy (primary GN overall) | | **Sub-Saharan Africa** | Lower | PSGN (acute), focal segmental GS (chronic) | **High-Yield:** In India and the Asian subcontinent, IgA nephropathy is the **most common primary glomerulonephritis** when considering all presentations (both acute and chronic), though post-streptococcal GN remains the most common **acute nephritic** syndrome in endemic areas. ### Pathophysiology of IgA Nephropathy 1. **Abnormal IgA1 glycosylation:** Galactose-deficient IgA1 (Gd-IgA1) is produced in excess 2. **Immune complex formation:** Gd-IgA1 complexes circulate and deposit in glomeruli 3. **Mesangial proliferation:** IgA deposition → complement activation (alternative pathway) → mesangial expansion 4. **Progressive glomerulosclerosis:** Over years, segmental sclerosis and crescent formation may occur ### Clinical Features **Mnemonic: IgA = Insidious, Gross/microscopic hematuria, Asymptomatic (often)** - **Presentation:** Recurrent gross hematuria (often after URI) or persistent microscopic hematuria - **Proteinuria:** Mild to moderate (usually <3.5 g/day); nephrotic syndrome is uncommon - **Renal function:** Variable; ranges from normal to progressive renal insufficiency - **Hypertension:** Present in ~50% at diagnosis - **Serum C3:** **Normal** (distinguishes from PSGN and MPGN) - **No systemic disease:** Isolated kidney involvement (primary IgAN) **Clinical Pearl:** IgA nephropathy can present with **episodic gross hematuria** coinciding with upper respiratory tract infections (URI), a pattern rarely seen in other GN types. This is called **synpharyngitic hematuria** and is highly suggestive of IgAN. ### Histologic Findings | Microscopy | Finding | | --- | --- | | **Light microscopy** | Mesangial proliferation (most common), focal segmental GN, or diffuse proliferation; crescents in severe disease | | **Immunofluorescence** | **IgA-dominant** (>IgG, >IgM) in mesangium; may have C3 co-deposition | | **Electron microscopy** | Electron-dense deposits in mesangium; subepithelial "humps" are absent (unlike PSGN) | ### Prognosis and Risk Factors **High-Yield:** IgA nephropathy has a **variable and unpredictable course**: - ~30% progress to ESRD within 10 years - ~50% remain stable or improve - Worse prognosis with: heavy proteinuria (>1 g/day), hypertension, reduced GFR at presentation, severe histologic lesions (crescents, sclerosis) ### Differentiation from PSGN ```mermaid flowchart TD A[Hematuria + Proteinuria]:::outcome --> B{Recent streptococcal infection?}:::decision B -->|Yes, 1–3 weeks prior| C[Check serum C3]:::action B -->|No or >3 weeks| D[Check serum C3]:::action C --> E{C3 level?}:::decision D --> E E -->|Low C3| F[PSGN likely]:::outcome E -->|Normal C3| G[IgA nephropathy likely]:::outcome G --> H[Confirm with kidney biopsy]:::action H --> I[IgA-dominant IF]:::outcome ``` **Warning:** Do not assume all hematuria after infection is PSGN — IgA nephropathy can also present with hematuria after URI, but C3 levels remain normal and the latency is not as stereotyped as PSGN.