What is the recommended workup and treatment for a patient with suspected Systemic Lupus Erythematosus (SLE) nephritis?

Workup for SLE Nephritis

Initial Clinical Assessment

All patients with SLE should undergo routine screening for lupus nephritis with urinalysis, urine protein-to-creatinine ratio (UPCR), serum creatinine, and blood pressure at every visit. 1

Key Laboratory Investigations

• Urinalysis with microscopy: Assess for proteinuria, hematuria, cellular casts (red blood cell casts are highly specific for glomerulonephritis), and pyuria 1
• Quantify proteinuria: 24-hour urine collection or spot UPCR (preferred for convenience) 1
• Serum creatinine and eGFR: Establish baseline kidney function and detect acute changes 1
• Complete blood count: Evaluate for cytopenias (anemia, thrombocytopenia, leukopenia/lymphopenia) which associate with disease activity and infection risk 1
• Serum albumin: Low levels indicate nephrotic syndrome and provide prognostic information 1

Immunologic Workup

• Anti-dsDNA antibodies: Associated with lupus nephritis activity, though limited predictive value for treatment response 1
• Complement levels (C3, C4): Low levels correlate with active disease and predict lupus nephritis, though not reliably predictive of flares 1, 2
• ANA testing: While typically positive in SLE, recognize that ANA-negative lupus nephritis exists and should not exclude the diagnosis if clinical suspicion is high 3
• Antiphospholipid antibodies: Essential for assessing thrombosis risk and pregnancy complications 1
• ANCA and anti-MPO: Consider in atypical presentations, as pauci-immune crescentic glomerulonephritis can rarely occur in SLE 4

Kidney Biopsy Indications

Kidney biopsy is essential for any SLE patient with proteinuria ≥0.5 g/24h (or ≥500 mg/g UPCR) with or without hematuria, cellular casts, or unexplained decline in kidney function. 1, 5

Expanded Biopsy Considerations

• Lower thresholds may be appropriate: Recent evidence shows 76% of patients with isolated proteinuria <1000 mg/24h had histologic lupus nephritis, including 35% with proliferative (Class III/IV) disease requiring aggressive therapy 2
• Risk factors for progression from low-grade proteinuria (0.2-0.5 g/g) include: low complement levels, shorter SLE duration, hypertension, diabetes, younger age, and hematuria 6
• Biopsy provides critical information: Determines ISN/RPS histologic class (I-VI), activity and chronicity indices, and excludes alternative diagnoses (thrombotic microangiopathy, ANCA-associated vasculitis, drug-induced injury) 1

Common Pitfall

Do not rely solely on serologic markers to exclude lupus nephritis—up to 50% of patients with low-grade proteinuria progress to overt nephritis within 1.2 years, and many have active treatable disease on biopsy despite minimal laboratory abnormalities 6, 2

Additional Diagnostic Considerations

Thrombotic Microangiopathy Evaluation

When lupus nephritis is suspected with concurrent thrombocytopenia and microangiopathic hemolytic anemia:

• ADAMTS13 activity and antibodies: Distinguish thrombotic thrombocytopenic purpura (activity <10%) 1
• Calculate PLASMIC score: Risk-stratify for TTP (score >5 indicates moderate/high risk) 1
• Antiphospholipid antibodies: Identify antiphospholipid syndrome-associated TMA 1
• Initiate plasma exchange and glucocorticoids while awaiting results in adults with high clinical suspicion 1

Cardiovascular and Metabolic Assessment

• Blood pressure monitoring: Target ≤130/80 mmHg in all lupus nephritis patients 1
• Lipid panel: Initiate statin therapy for LDL >100 mg/dL 1
• Assess for diabetes and other cardiovascular risk factors: Critical for long-term outcomes 1

Monitoring Parameters

Response Assessment Timeline

Treatment response should be evaluated at 3-4 months, with expectations of ≥25% proteinuria reduction by 3 months, ≥50% reduction by 6 months, and target <0.5-0.7 g/g by 12 months. 1, 7, 5

• Complete response: Proteinuria <0.5 g/g (50 mg/mmol) with stable/improved kidney function (±10-15% of baseline) within 6-12 months 1
• Partial response: ≥50% proteinuria reduction to <3 g/g (300 mg/mmol) with stable kidney function within 6-12 months 1
• No response: Failure to achieve partial or complete response by 6-12 months 1

Ongoing Surveillance

• Urine sediment, UPCR, serum creatinine: Monitor at each visit for early detection of flares 1
• Immunologic markers (anti-dsDNA, C3, C4): Supplemental information only, as changes have limited ability to predict treatment response 1
• CRP elevation: Should prompt evaluation for superimposed infection, especially if >50 mg/L 1