What is the workup for lupus nephritis?

Workup for Lupus Nephritis

All patients with suspected lupus nephritis require kidney biopsy to confirm diagnosis, determine histologic class, and guide treatment decisions, as clinical and serologic findings alone are insufficient to establish the diagnosis or predict disease severity. 1

Initial Clinical Assessment

Laboratory Evaluation at Diagnosis

Perform the following baseline tests at initial evaluation:

• Renal function markers: Serum creatinine, estimated GFR (eGFR), serum albumin 1
• Urinalysis: 24-hour urine collection for protein-creatinine ratio (PCR), microscopic urinary sediment evaluation for red blood cells and casts 1
• Complete blood count: Assess for anemia, leukopenia, lymphopenia, and thrombocytopenia 1, 2
• Blood pressure measurement: Hypertension is both a manifestation and predictor of poor outcomes 1

Immunologic Workup

Essential serologic markers include:

• Anti-dsDNA antibodies: Use quantitative assay (preferably same method/laboratory for monitoring); positive in approximately 70% of lupus nephritis cases 1, 2
• Complement levels: C3 and C4 (low levels indicate active disease and consumption) 1, 2
• ANA: Positive in ~95% of SLE patients, though not specific for nephritis 1, 2
• Anti-C1q antibodies: Found in nearly 100% of patients with active lupus nephritis; critical negative predictive value for flares 1
• Antiphospholipid antibodies: Measure at baseline to assess thrombotic risk and guide anticoagulation decisions 1

Important caveat: Some patients with biopsy-proven lupus nephritis (particularly membranous type) may be anti-dsDNA negative; in these cases, anti-nucleosome antibodies can be used for monitoring 1. Seronegative lupus nephritis exists and should not exclude the diagnosis when histopathology is consistent 3.

Additional Baseline Testing

• Lipid profile: Assess dyslipidemia requiring statin therapy 1
• Infectious disease screening: Test for hepatitis B, tuberculosis history, and herpes zoster 4
• ADAMTS13 activity and antibodies: If thrombotic microangiopathy is suspected 1, 4

Kidney Biopsy

Kidney biopsy is mandatory for:

• Confirming lupus nephritis diagnosis 1
• Determining WHO/ISN-RPS histologic class (I-VI) 1, 2
• Assessing activity and chronicity indices 1
• Distinguishing active inflammation from chronic damage 5
• Evaluating for concurrent pathologies (e.g., thrombotic microangiopathy, antiphospholipid syndrome-associated nephropathy) 1

Indications for kidney biopsy:

• Proteinuria >0.5 g/24 hours (or PCR >50 mg/mmol) 1, 2
• Active urinary sediment with red blood cells and/or casts 1, 2
• Rising serum creatinine without alternative explanation 1

Repeat biopsy should be considered when:

• Worsening or refractoriness to treatment (failure to decrease proteinuria by ≥50%, persistent proteinuria beyond 1 year, worsening GFR) 1
• Disease relapse to demonstrate histologic progression 1
• Uncertainty about diagnosis remains 5

Key histopathologic finding: "Full house" immunofluorescence pattern (granular deposition of IgG, IgA, IgM, C1q, and C3) is highly specific for lupus nephritis, even in seronegative cases 3.

Monitoring Parameters During Follow-Up

Schedule visits every 2-4 weeks for the first 2-4 months after diagnosis, then every 3-6 months lifelong: 1

• Body weight and blood pressure at each visit 1
• Serum creatinine, eGFR, and serum albumin 1
• Proteinuria (PCR) and urinary sediment 1
• Serum C3, C4, and anti-dsDNA antibody levels 1
• Complete blood count 1
• Lipid profile monitored intermittently 1

Do not use ANA for monitoring disease activity or progression, as repeating ANA after initial positive result is neither appropriate nor cost-effective. 1

Common Pitfalls

• Relying solely on serology: Approximately 30% of lupus nephritis patients may be anti-dsDNA negative, particularly those with membranous nephritis 1, 3
• Delaying biopsy: Clinical parameters alone cannot reliably predict histologic class or guide optimal treatment 1, 2
• Ignoring serologically active but clinically quiescent disease: Some patients maintain elevated anti-dsDNA without clinical manifestations long-term 1
• Missing concurrent thrombotic microangiopathy: Always test for ADAMTS13 and antiphospholipid antibodies when TMA is suspected, as management differs significantly 1, 4