Post-Infectious Glomerulonephritis: Complement and Serologic Profile
Post-infectious glomerulonephritis (PIGN) characteristically causes low C3 with normal C4, but ASO titers may be normal in up to 20-30% of cases, particularly when the infection is non-streptococcal or when the patient presents late after the initial infection. 1
Typical Complement Pattern in PIGN
The hallmark laboratory finding in PIGN is low C3 with normal C4, which indicates alternative complement pathway activation rather than classical pathway activation. 1
- Low C3 is present in approximately 90% of cases at presentation 1
- C4 typically remains normal, distinguishing PIGN from lupus and other classical pathway disorders 1
- C3 levels should normalize within 8-12 weeks after disease onset in uncomplicated cases 1
- Persistently low C3 beyond 12 weeks mandates kidney biopsy to exclude C3 glomerulonephritis (C3GN), which is a distinct disease entity requiring different management 2, 1
ASO Titers: Not Always Elevated
ASO titers are not universally elevated in PIGN, and normal titers do not exclude the diagnosis. 1
- ASO titers are elevated in only 70-80% of post-streptococcal cases, particularly when pharyngitis was the preceding infection 1
- Impetigo-associated PIGN has lower rates of ASO elevation because skin infections produce less robust ASO responses 1
- Non-streptococcal PIGN (from Staphylococcus, pneumococcus, or other organisms) will have normal ASO titers 3, 4
- Alternative streptococcal antibodies (anti-DNAse B, anti-hyaluronidase) should be measured when ASO is normal but clinical suspicion remains high 2, 1
Clinical Scenario: Low C3, Normal C4, Normal ASO
When you encounter low C3, normal C4, and normal ASO, consider this diagnostic approach:
First: Confirm PIGN Diagnosis
- Document recent infection history: pharyngitis 1-2 weeks prior or impetigo 4-6 weeks prior 2, 1
- Obtain anti-DNAse B and anti-hyaluronidase antibodies, which may be positive when ASO is negative 2, 1
- Culture any active skin or throat infections 2
- Consider non-streptococcal infections (Staphylococcus aureus, pneumococcus) which cause PIGN with normal ASO 3, 4
Second: Rule Out Alternative Diagnoses
- Exclude lupus nephritis: check ANA, anti-dsDNA (lupus causes low C3 AND low C4) 1, 5
- Exclude ANCA vasculitis: check PR3-ANCA and MPO-ANCA 2, 1
- Exclude anti-GBM disease: check anti-GBM antibodies 2, 1
- Exclude cryoglobulinemia: check cryoglobulins and rheumatoid factor 2, 1
Third: Monitor for C3GN
- If C3 remains low beyond 12 weeks, perform kidney biopsy to distinguish PIGN from C3 glomerulonephritis 2, 1
- C3GN is a distinct disease with ongoing complement dysregulation, poor prognosis, and requires different treatment 6, 7
- PIGN and C3GN can have overlapping pathologic features on biopsy, but clinical course distinguishes them 7
Common Pitfalls to Avoid
Do not withhold antibiotics even when ASO is normal or infection has resolved—the goal is to reduce antigenic load, not treat active infection. 1
Do not assume normal ASO excludes PIGN—obtain additional streptococcal antibodies and consider non-streptococcal causes. 1, 3
Do not delay kidney biopsy if C3 remains low beyond 12 weeks, as this indicates possible C3GN requiring immunosuppression rather than supportive care alone. 2, 1
Do not use immunosuppression for typical PIGN—the disease is self-limited with excellent prognosis, and corticosteroids are reserved only for severe crescentic disease with rapidly progressive glomerulonephritis. 1
Monitoring Strategy
- Recheck C3 and C4 every 2-4 weeks initially to confirm normalization trajectory 5
- Monitor serum creatinine, urinalysis with microscopy, and urine protein-to-creatinine ratio 1
- If C3 fails to normalize by 8-12 weeks, proceed to kidney biopsy 2, 1
- Continue monitoring blood pressure and manage hypertension with diuretics and sodium restriction 1