What is the initial treatment for lupus nephritis?

Initial Treatment for Lupus Nephritis

The initial treatment for lupus nephritis should consist of mycophenolic acid (MPA) with a target dose of mycophenolate mofetil (MMF) 3 g/day for 6 months or low-dose intravenous cyclophosphamide, plus glucocorticoids and hydroxychloroquine. 1

Induction Therapy Components

First-Line Medications

1. Immunosuppressive agent (choose one):

   • Mycophenolate mofetil (MMF) at 3 g/day for 6 months
   • Low-dose intravenous cyclophosphamide

2. Glucocorticoids:

   • Initial IV methylprednisolone pulses: 500-750 mg for 3 consecutive days
   • Followed by oral prednisone: 0.5 mg/kg/day for 4 weeks
   • Taper to ≤10 mg/day by 4-6 months

3. Hydroxychloroquine:

   • 200-400 mg/day for all SLE patients
   • Continue indefinitely to reduce flares and improve outcomes

Treatment Modifications Based on Disease Severity

For patients with adverse prognostic factors:

• Acute deterioration in renal function
• Substantial cellular crescents
• Fibrinoid necrosis

Consider higher doses of cyclophosphamide (0.75-1 g/m² monthly for 6 months) 1

Alternative Therapies

When MMF or cyclophosphamide are contraindicated, not tolerated, or unavailable:

• Azathioprine (2 mg/kg/day) may be considered, especially if pregnancy is contemplated 1
• Note: Azathioprine is associated with a higher flare risk

Adjunctive Treatments

1. Renal and cardiovascular protection:

   • ACE inhibitors or ARBs for proteinuria or hypertension
   • Statins for persistent dyslipidemia (target LDL <100 mg/dL)
   • Calcium and vitamin D supplementation

2. Additional considerations:

   • Immunizations with non-live vaccines
   • Anticoagulation in nephrotic syndrome with serum albumin <20 g/L, especially with anti-phospholipid antibodies

Monitoring Protocol

• Initial monitoring: Every 2-4 weeks for first 2-4 months after diagnosis or flare
• Regular assessment of:
  • Body weight and blood pressure
  • Serum creatinine, eGFR, albumin
  • Proteinuria and urinary sediment
  • Complement levels (C3, C4)
  • Anti-dsDNA antibody levels
  • Complete blood count
  • Liver function tests
• Echocardiography: At baseline and every 3-6 months
• ECG monitoring for conduction abnormalities
• Regular ophthalmologic exams for hydroxychloroquine toxicity

Treatment Goals

• Partial renal response by 6 months
• Complete renal response by 12 months (proteinuria <50 mg/mol and normal/near-normal renal function)

Maintenance Phase

After achieving improvement (typically 6 months):

• Reduce MMF to maintenance dose (2 g/day)
• Continue for at least 36 months
• Maintain low-dose prednisone (5-7.5 mg/day)
• Continue hydroxychloroquine indefinitely

Important Considerations

• Avoid prolonged high-dose glucocorticoids due to toxicity concerns 1
• The combination of immunosuppressants with corticosteroids has significantly improved survival in lupus nephritis patients 2, 3
• Despite advances in treatment, approximately 10% of patients still progress to end-stage kidney disease 4
• Novel agents like belimumab, voclosporin, and obinutuzumab have shown promise in recent studies, but the standard initial approach remains MMF or cyclophosphamide with corticosteroids 4

Common Pitfalls to Avoid

• Delaying treatment initiation in active lupus nephritis
• Inadequate dosing of immunosuppressive agents
• Overly rapid tapering of corticosteroids
• Discontinuing hydroxychloroquine
• Insufficient monitoring of disease activity and medication side effects
• Failure to address cardiovascular risk factors and bone health