What is the recommended approach for a nephritis screen?

Nephritis Screen: Recommended Diagnostic Approach

A nephritis screen should include urinalysis with microscopy (looking for proteinuria >0.5g/24h or spot protein/creatinine ratio >0.5, hematuria >5 RBC/hpf, and cellular casts), serum creatinine, and in most cases with confirmed abnormalities, proceed directly to renal biopsy for definitive diagnosis and classification. 1

Initial Laboratory Evaluation

The cornerstone of nephritis screening involves specific urinary findings:

• Proteinuria threshold: Persistent proteinuria ≥0.5 g/24 hours (or spot urine protein/creatinine ratio >0.5) is the primary screening threshold that should prompt suspicion of glomerulonephritis 1
• Active urinary sediment: Look for >5 RBC/hpf, >5 WBC/hpf (without infection), or presence of RBC/WBC casts 1
• Cellular casts: Red blood cell or white blood cell casts are highly specific for glomerular inflammation and significantly increase suspicion 1, 2

When to Proceed to Renal Biopsy

Renal biopsy is the definitive diagnostic test and should not be delayed when clinical criteria are met. 1

Clear Indications for Biopsy:

• Proteinuria ≥1.0 g/24 hours alone 1
• Proteinuria ≥0.5 g/24 hours PLUS hematuria or cellular casts 1
• Increasing serum creatinine without compelling alternative causes 1
• GFR <30 mL/min with normal kidney size and evidence of active disease 1

Timing Considerations:

• Perform biopsy within the first month after disease onset, preferably before starting immunosuppressive treatment 1
• Do not delay biopsy even with advanced GFR decline if kidney size is normal and active disease is present 1

Adequate Biopsy Requirements

For proper evaluation, the biopsy must include 1:

• Minimum 10 glomeruli for light microscopy evaluation
• Light microscopy stains: H&E, PAS, Masson's trichrome, and silver stain
• Immunofluorescence: IgG, C3, IgA, IgM, C1q, κ and λ light chains
• Electron microscopy for ultrastructural evaluation

Critical Pitfalls to Avoid

Do not rely solely on clinical parameters or serological tests to rule out nephritis—they cannot accurately predict histological findings. 1 The threshold for biopsy should be low because:

• Clinical presentation alone is insufficient for diagnosis 1
• Serological markers (complement levels, autoantibodies) provide supportive but not definitive information 3, 2
• Histological classification (ISN/RPS Classes I-VI for lupus nephritis) is essential for guiding treatment decisions 1

Imaging Has Limited Role

Imaging is NOT part of the standard nephritis screen. 4

• Ultrasound, CT, and MRI are not beneficial for diagnosing glomerulonephritis 4
• Imaging may be useful only to exclude obstruction or assess kidney size before biopsy 5
• Do not confuse nephritis (glomerular disease) with pyelonephritis (infection), which has different diagnostic algorithms 5, 6

Additional Serological Testing

While not replacing biopsy, consider these tests based on clinical context 3, 2:

• Complement levels (C3, C4) for post-infectious GN or lupus nephritis
• ANA and anti-dsDNA if lupus nephritis suspected
• ANCA panel if vasculitis suspected
• Anti-GBM antibodies if rapidly progressive GN
• Serum and urine protein electrophoresis if monoclonal gammopathy suspected

Clinical Context Matters

The most common causes of nephritic syndrome include 2:

• Post-infectious glomerulonephritis
• IgA nephropathy
• Lupus nephritis
• ANCA-associated vasculitis

The specific histological diagnosis from biopsy determines treatment strategy, as different classes require vastly different immunosuppressive regimens. 1 For example, lupus nephritis Class III/IV requires aggressive immunosuppression, while Class I/II does not require specific therapy 1.