What is the full initial secondary lab workup for a new presentation of suspected glomerulonephritis (GN)?

Initial Secondary Laboratory Workup for Suspected Glomerulonephritis

The full initial secondary laboratory workup for a new presentation of suspected glomerulonephritis should include serum creatinine, urinalysis with microscopy, 24-hour urine protein collection, serum complement levels (C3 and C4), antinuclear antibody, anti-double stranded DNA, ANCA (anti-MPO and anti-PR3), anti-GBM antibodies, serum protein electrophoresis, and hepatitis serologies. 1

Core Laboratory Tests

Kidney Function and Urinalysis

• Serum creatinine and eGFR (using CKD-EPI equation for adults, modified Schwartz for children) 1
• Complete urinalysis with microscopy (looking specifically for red cell casts, acanthocytes, and glomerular hematuria) 1
• 24-hour urine protein collection or spot urine protein-to-creatinine ratio 1
• Complete blood count with platelets 1

Immunologic Workup

• Serum complement levels (C3 and C4) 1
• Antinuclear antibody (ANA) and anti-double stranded DNA (anti-dsDNA) 1, 2
• ANCA panel with specificity for:
  • Anti-myeloperoxidase (MPO-ANCA)
  • Anti-proteinase 3 (PR3-ANCA) 1, 2
• Anti-glomerular basement membrane (anti-GBM) antibodies 1, 2

Additional Serologies

• Hepatitis B and C serologies 1
• HIV testing 1
• Serum protein electrophoresis and immunofixation 1
• Cryoglobulins 1
• Rheumatoid factor 1

Disease-Specific Testing

For Suspected Post-Infectious GN

• Anti-streptolysin O (ASO) titers
• Anti-DNAse B antibodies
• Anti-hyaluronidase antibodies
• Blood cultures if endocarditis suspected 1

For Suspected IgA Nephropathy

• No specific serologic marker, diagnosis requires kidney biopsy 1

For Suspected Rapidly Progressive GN

• All of the above tests should be expedited
• Kidney biopsy should be performed urgently but should not delay treatment if clinical suspicion is high with positive ANCA or anti-GBM antibodies 1, 2

Interpretation and Clinical Correlation

• Low C3 with normal C4: Suggests alternative complement pathway activation (seen in C3GN, post-infectious GN) 1
• Low C3 and C4: Suggests classical complement pathway activation (seen in lupus nephritis, cryoglobulinemia) 1
• Positive ANCA: Suggests ANCA-associated vasculitis 2
• Positive anti-GBM: Suggests anti-GBM disease (Goodpasture's syndrome) 2
• Tea-colored urine with proteinuria, RBC casts, and deformed RBCs suggests glomerular source of hematuria 1

Common Pitfalls to Avoid

1. Delaying treatment in rapidly progressive GN: In cases with high clinical suspicion and positive ANCA or anti-GBM antibodies, treatment should not be delayed while waiting for kidney biopsy results 1, 2

2. Incomplete serologic workup: Missing key serologies can lead to delayed diagnosis and treatment 1

3. Relying solely on dipstick urinalysis: Microscopic examination is essential to identify RBC casts and acanthocytes that confirm glomerular hematuria 1

4. Neglecting to rule out infections: Always exclude infection before initiating immunosuppression 1

5. Overlooking monoclonal gammopathies: Some cases of GN are associated with monoclonal gammopathies that require specific treatment approaches 3

Remember that kidney biopsy remains the gold standard for definitive diagnosis of glomerulonephritis and should be performed when feasible to guide treatment decisions and provide prognostic information 1, 2.