Treatment of Lupus Nephritis
The recommended treatment for lupus nephritis includes mycophenolic acid (MPA) or low-dose intravenous cyclophosphamide combined with glucocorticoids and hydroxychloroquine, with treatment selection guided by renal biopsy classification and presence of adverse prognostic factors. 1, 2
Diagnostic Approach
- Renal biopsy is essential for guiding treatment decisions
- Any reproducible proteinuria ≥0.5 g/24h with glomerular hematuria and/or cellular casts warrants biopsy
- Use International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system
Initial Treatment Based on Biopsy Class
Class III (Focal) or IV (Diffuse) Proliferative LN:
First-line options:
- MPA (MMF target dose: 3 g/day for 6 months) OR
- Low-dose IV cyclophosphamide (total dose 3 g over 3 months)
- PLUS glucocorticoids: IV methylprednisolone 500-750 mg pulses for 3 days, followed by oral prednisone 0.5 mg/kg/day, tapering to ≤10 mg/day by 4-6 months
For patients with adverse prognostic factors (acute deterioration in renal function, substantial cellular crescents, fibrinoid necrosis):
- Higher-dose cyclophosphamide (0.75-1 g/m² monthly for 6 months)
Class V (Membranous) LN with nephrotic-range proteinuria:
- MPA (MMF target dose: 3 g/day for 6 months) with oral prednisone (0.5 mg/kg/day)
- Alternative options: cyclophosphamide, calcineurin inhibitors (ciclosporin, tacrolimus), or rituximab
Milder disease without adverse prognostic factors:
- Azathioprine (2 mg/kg/day) may be considered as an alternative to MPA or cyclophosphamide
- Note: Associated with higher flare risk 1
Maintenance Therapy
- Continue immunosuppression for at least 3 years after initial improvement
- Options:
- MPA at lower doses (MMF target dose: 2 g/day) OR
- Azathioprine (2 mg/kg/day)
- PLUS low-dose prednisone (5-7.5 mg/day)
- Patients who responded to MPA should remain on MPA for maintenance 1
- If pregnancy is contemplated, switch from MPA to azathioprine at least 3 months before conception 2
Treatment for Refractory Disease
- For patients failing MPA: Switch to cyclophosphamide
- For patients failing cyclophosphamide: Switch to MPA
- Rituximab can be considered for patients failing both agents 1
Adjunctive Treatments
- Hydroxychloroquine: Recommended for ALL patients with lupus nephritis to reduce renal flares and limit damage 1, 2, 3
- ACE inhibitors or ARBs: For patients with proteinuria or hypertension
- Statins: For persistent dyslipidemia (target LDL <100 mg/dl)
- Calcium and vitamin D supplementation: To prevent osteoporosis
- Immunizations: Non-live vaccines recommended
- Anticoagulation: Consider in nephrotic syndrome with serum albumin <20 g/L, especially with anti-phospholipid antibodies
Monitoring
- Initial monitoring: Every 2-4 weeks for first 2-4 months
- Regular assessment of:
- Body weight, blood pressure
- Serum creatinine, eGFR, albumin
- Proteinuria, urinary sediment
- Complement levels (C3, C4), anti-dsDNA antibodies
- Complete blood count
- Treatment goals:
- Partial renal response by 6 months
- Complete renal response (proteinuria <0.5 g/24h with normal/near-normal renal function) by 12 months
Common Pitfalls and Caveats
- Delayed biopsy: Don't rely on clinical parameters alone to guide treatment
- Inadequate initial immunosuppression: Undertreatment leads to worse outcomes
- Prolonged high-dose glucocorticoids: Aim to taper to ≤10 mg/day by 4-6 months
- Omitting hydroxychloroquine: Should be prescribed for all patients
- Premature discontinuation of maintenance therapy: Continue for at least 3 years
- Inadequate monitoring: Regular assessment is essential to detect flares early
- Failure to adjust medications before pregnancy: Switch from MPA to azathioprine at least 3 months before conception
The treatment approach to lupus nephritis has evolved significantly, with current guidelines emphasizing the importance of biopsy-guided therapy, combination treatment with immunosuppressants and glucocorticoids, and long-term maintenance therapy to prevent flares and preserve renal function.