What are the differences between post‑streptococcal glomerulonephritis (PSGN) and IgA nephropathy (Berger disease)?

Key Differences Between Post-Streptococcal Glomerulonephritis and IgA Nephropathy

Post-streptococcal glomerulonephritis (PSGN) is an acute, infection-triggered, self-limited disease requiring only supportive care and antibiotics, while IgA nephropathy (IgAN) is a chronic, progressive immunologic disease requiring long-term immunosuppressive therapy and RAS blockade.

Clinical Presentation & Timing

PSGN presents acutely 1-3 weeks after pharyngitis or 4-6 weeks after impetigo with classic nephritic syndrome: sudden onset edema, hypertension, gross hematuria, and oliguria 1. The disease follows a predictable temporal relationship to streptococcal infection.

IgAN typically presents with recurrent episodes of gross hematuria coinciding with or immediately following upper respiratory infections (synpharyngitic hematuria), or is discovered incidentally with persistent microscopic hematuria and proteinuria 2, 3. The presentation is more insidious and chronic.

Laboratory Findings

Complement Levels

• PSGN: Low C3 that normalizes within 8-12 weeks 1. Persistently low C3 beyond 12 weeks suggests an alternative diagnosis like C3 glomerulonephritis 4.
• IgAN: Normal complement levels in most cases 5. Hypocomplementemia C3 is an independent differentiating factor favoring infection-related disease over primary IgAN 5.

Serologic Markers

• PSGN: Elevated anti-streptolysin O (ASO), anti-DNAse B, and anti-hyaluronidase antibodies 4
• IgAN: No specific serologic markers; may have elevated serum IgA 1

Acute Kidney Injury

PSGN commonly presents with acute kidney injury that resolves with supportive care 5, 6. IgAN typically has preserved kidney function at presentation unless there is rapidly progressive disease with crescents 2, 3.

Kidney Biopsy Findings

Light Microscopy

• PSGN: Diffuse endocapillary proliferative pattern with neutrophilic infiltration 1, 7
• IgAN: Mesangial proliferation with variable endocapillary proliferation and crescents 2

Immunofluorescence

• PSGN: Granular deposits of C3 and IgG in capillary walls and mesangium; C3 typically more prominent than immunoglobulins 1
• IgAN: Dominant or co-dominant mesangial IgA deposits with C3 2, 8

Electron Microscopy

• PSGN: Characteristic subepithelial "hump-like" electron-dense deposits 1, 7, 5
• IgAN: Mesangial and paramesangial electron-dense deposits; subepithelial humps are absent 5

Critical Diagnostic Pitfall: IgA-Dominant Infection-Related GN

A crucial entity that must be distinguished from primary IgAN is IgA-dominant postinfectious glomerulonephritis, which occurs primarily in elderly and diabetic patients with staphylococcal infections (including MRSA) 1. This variant shows:

• Hypocomplementemia (present in majority of cases)
• IgA-dominant deposits on biopsy
• Association with poor renal outcomes
• Must NOT be treated with corticosteroids 1

The key differentiating features from primary IgAN include: hypocomplementemia C3, acute kidney injury, low serum albumin, diffuse foot process effacement, and higher Lupus Nephritis Activity Index scores 5.

Treatment Approach

PSGN Management 1, 4

1. Antibiotics: Penicillin (or erythromycin if allergic) to decrease antigenic load, even without persistent infection
2. Supportive care: Diuretics, antihypertensives, fluid/salt restriction
3. Dialysis: Only if necessary for severe complications
4. Corticosteroids: Reserved only for severe crescentic disease (anecdotal evidence only)
5. Duration: Symptoms typically resolve within weeks; proteinuria and hematuria may persist for months

IgAN Management 2, 3, 8

1. RAS blockade: Optimized maximally tolerated ACEi or ARB for all patients with proteinuria >0.5-1 g/day (1B recommendation)
2. Blood pressure targets: <130/80 mmHg if proteinuria <1 g/day; <125/75 mmHg if proteinuria >1 g/day
3. SGLT2 inhibitors: For patients at risk of progressive kidney function loss (2B recommendation) 3
4. Sparsentan: Dual endothelin-angiotensin receptor antagonist where approved (2B recommendation) 3
5. Immunosuppression: For high-risk patients with persistent proteinuria >1 g/day despite optimized supportive care
6. Long-term monitoring: Lifelong follow-up required due to chronic progressive nature

Prognosis

PSGN has excellent prognosis in children with >95% complete recovery 6. Adults may have residual proteinuria or hypertension requiring monitoring. IgA-dominant infection-related GN has much worse outcomes with <20% returning to baseline kidney function and frequent dialysis requirement 4, 5.

IgAN is a chronic progressive disease with 30-40% developing kidney failure over 20-30 years. Risk stratification based on proteinuria (>1 g/day), hypertension, reduced eGFR at presentation, and Oxford MEST-C histologic scores guides treatment intensity 2.

Superimposition Cases

Rarely, PSGN can occur in patients with pre-existing IgAN 9, 10, 11. In these cases, the second biopsy shows increased C3 deposition, decreased IgA deposits, endocapillary proliferation, and subepithelial humps superimposed on the original mesangial IgA pattern. Treatment focuses on the acute PSGN component with supportive care, followed by resumption of IgAN-specific therapy once the acute episode resolves.