What tests are required to check for renal involvement in a patient with systemic lupus erythematosus (SLE)?

Testing for Renal Involvement in Lupus

All patients with SLE should undergo regular screening with urinalysis (dipstick), quantified proteinuria, serum creatinine/eGFR, and complement levels (C3/C4) with anti-dsDNA antibodies, as kidney involvement can remain asymptomatic for prolonged periods and early detection significantly improves outcomes. 1

Initial Screening Tests

Urinary Assessment

• Dipstick urinalysis to detect proteinuria ≥2+ or hematuria 1
• Urine sediment microscopy looking specifically for:
  • Red blood cell casts 1
  • White blood cell casts 1
  • Acanthocytes (≥5%) 1
• Quantified proteinuria using either:
  • Spot urine protein-to-creatinine ratio (UPCR) 1, 2
  • 24-hour urine protein collection 2
  • Threshold for further investigation: ≥500 mg/24 hours or UPCR ≥500 mg/g 1

Renal Function Assessment

• Serum creatinine to calculate eGFR 1, 3
• Look for abnormal eGFR below expected level for age, or decreasing eGFR with no other attributable cause 1
• Serial monitoring is critical as a single normal value does not exclude lupus nephritis 1

Immunologic Testing

• Complement levels (C3 and C4): Low levels significantly associated with active renal disease 1, 3
• Anti-dsDNA antibodies: Correlates with lupus nephritis activity 1
• Anti-C1q antibodies (when available): Should be considered in suspected lupus nephritis 1
• Antiphospholipid antibodies (aPL): Essential testing as renal thrombotic microangiopathy may occur 1

When to Proceed to Kidney Biopsy

Kidney biopsy should be performed when there is persistent proteinuria ≥500 mg/24 hours (or UPCR ≥500 mg/g) and/or unexplained decrease in GFR, as clinical findings do not correlate reliably with histologic severity. 1

Biopsy Indications

• Proteinuria ≥500 mg/24 hours without alternative explanation 1
• Active urinary sediment (casts, acanthocytes) 1
• Rising creatinine or declining eGFR unexplained by other causes 1
• Nephrotic-range proteinuria (>3.5 g/day) 1, 3

Critical Biopsy Requirements

• Must be read by experienced kidney pathologist 1
• ISN/RPS classification system should be used 1
• Electron microscopy (when available) provides crucial ultrastructural details about podocyte injury and immune deposit location 1
• Assessment of both active and chronic lesions to guide treatment decisions 1

Important Clinical Pitfalls

Don't Miss These Key Points

• Proteinuria severity varies considerably in active nephritis and can appear "insignificant" despite severe disease 1
• Kidney involvement can be silent/asymptomatic for extended periods, requiring active surveillance 1
• Higher risk populations require heightened vigilance: Asian, African/Caribbean, Hispanic descent, and childhood-onset SLE 1
• Clinical findings do not correlate with histologic severity—biopsy remains indispensable 1
• ANA-negative lupus nephritis exists: Full-house nephropathy on biopsy may occur despite negative serologies 4

Monitoring Frequency

• Initial phase: Frequent monitoring (twice weekly to weekly) when renal impairment first suspected 5
• Stable chronic disease: Every 3-6 months for creatinine, urinalysis, and UPCR 5
• After medication changes: More frequent monitoring until stable 5
• Never use fixed schedules without considering individual factors like medication burden and comorbidities 5

Holistic Assessment Approach

A single test result is insufficient—serial measurements of clinical, urinary, and laboratory parameters over time are essential for accurate diagnosis and management decisions. 1

The combination of elevated creatinine, severe hypoalbuminemia, and low complement levels has established predictive value for kidney involvement and 5-year survival 3. However, the absence of these findings does not exclude lupus nephritis, particularly in early disease 1.