Laboratory Evaluation of Post-Streptococcal Glomerulonephritis
For suspected PSGN, obtain urinalysis with microscopy, serum creatinine, C3 and C4 complement levels, and streptococcal antibody titers (ASO, anti-DNAse B, anti-hyaluronidase) as your core diagnostic panel. 1
Essential Laboratory Tests
Urinalysis and Kidney Function
- Urinalysis with microscopy showing glomerular hematuria with red blood cell casts and proteinuria (measure albumin-creatinine ratio or protein-creatinine ratio) is the key diagnostic criterion 1
- Serum creatinine and eGFR to assess for acute kidney injury, which occurs in severe cases 1
- Microscopic or gross hematuria is the hallmark finding 2, 3
Complement Studies
- C3 complement level is low in more than 90% of PSGN cases and is the hallmark finding 1, 3
- C4 complement level typically remains normal, which helps differentiate PSGN from other forms of glomerulonephritis like lupus nephritis 1
- The decrease in C3 is typically seen earlier than the rise in streptococcal antibody titers 3
- C3 should normalize within 8-12 weeks; persistently low C3 beyond 12 weeks warrants kidney biopsy to exclude C3 glomerulonephritis 1
Streptococcal Serology
- Anti-streptolysin O (ASO) titers are valuable for confirming prior streptococcal infection 4, 2
- Anti-DNAse B antibodies should be measured when ASO is normal but clinical suspicion remains high, as ASO may be negative in up to 10% of cases 1
- Anti-hyaluronidase antibodies serve as an additional streptococcal marker 1
- These antibody titers reflect past immunologic events, not acute infection, and are most useful 1-3 weeks after the initial streptococcal infection 4
Additional Laboratory Tests to Exclude Other Diagnoses
When the diagnosis is uncertain or atypical, obtain the following to rule out alternative causes of glomerulonephritis:
- ANA and anti-dsDNA to exclude lupus nephritis (which causes low C3 AND low C4) 1
- ANCA (PR3-ANCA and MPO-ANCA) to exclude ANCA-associated vasculitis 1
- Anti-GBM antibodies to exclude anti-GBM disease 1
- Cryoglobulins and rheumatoid factor to exclude cryoglobulinemic glomerulonephritis 1
Monitoring Parameters
- Serum creatinine, urinalysis with microscopy, and urine protein-to-creatinine ratio should be monitored serially 1
- Blood pressure monitoring is critical as hypertension is a major sequela in the first 7-10 days 3
- Electrolytes to monitor for hyperkalemia, especially if using ACE inhibitors or ARBs 3
Common Pitfalls to Avoid
- Do not rely solely on ASO titers: Anti-DNAse B and anti-hyaluronidase antibodies may be positive when ASO is negative, particularly after skin infections 1
- Do not dismiss the diagnosis if C3 is normal initially: Complement activation may precede clinical onset, and C3 may drop after initial presentation 5
- Do not delay kidney biopsy if C3 remains low beyond 12 weeks: This suggests an alternative diagnosis such as C3 glomerulonephritis rather than PSGN 1
- Do not confuse carrier state with active infection: Streptococcal antibody titers confirm prior infection, not current pharyngitis 4
When to Consider Kidney Biopsy
Kidney biopsy is indicated when 6, 1:
- Diagnosis is uncertain or presentation is atypical
- C3 remains persistently low beyond 12 weeks
- Rapidly progressive glomerulonephritis is suspected
- Alternative diagnoses need to be excluded