What is the treatment for Lupus Nephritis (LN)?

Treatment of Lupus Nephritis (LN)

The recommended first-line treatment for active lupus nephritis is glucocorticoids plus mycophenolic acid analogs (MPAA), with the addition of belimumab or calcineurin inhibitors as effective options for improving outcomes and reducing mortality. 1, 2

Diagnosis and Classification

• Renal biopsy is essential for diagnosis and treatment planning when there is:

  • Reproducible proteinuria ≥0.5 g/24h (especially with glomerular hematuria/cellular casts)
  • Unexplained decrease in GFR 1, 2

• Treatment is guided by ISN/RPS classification:

  • Class III (focal) or IV (diffuse) proliferative LN
  • Class V (membranous) LN
  • Mixed classes (III/V or IV/V)

Initial Treatment Regimens

For Class III or IV LN (with or without membranous component):

1. Glucocorticoids:

   • IV methylprednisolone 500-750 mg daily for 1-3 days
   • Followed by oral prednisone 0.35-1.0 mg/kg/day (not exceeding 80 mg/day)
   • Taper to ≤10 mg/day by 4-6 months 1

2. Plus one of the following:

   • MPAA: Mycophenolate mofetil (MMF) 2-3 g/day divided in two doses or mycophenolic acid sodium at equivalent dose 1, 2
   • Low-dose IV cyclophosphamide: 500 mg every 2 weeks for 6 doses (total 3g) 1
   • MPAA + calcineurin inhibitor: Voclosporin 23.7 mg twice daily (for eGFR >45 ml/min/1.73m²) or tacrolimus 1, 2
   • Belimumab + MPAA or cyclophosphamide: Belimumab 10 mg/kg IV every 2 weeks for 3 doses then every 4 weeks 1

3. Additional therapy:

   • Hydroxychloroquine (improves outcomes and reduces mortality) 2
   • RAAS blockade (ACE inhibitors or ARBs) for proteinuria >500 mg/day or hypertension 2

For Pure Class V LN with nephrotic-range proteinuria:

• MPAA (MMF 3 g/day) + oral prednisone (0.5 mg/kg/day) as first-line therapy 1, 2
• Alternative options: cyclophosphamide, calcineurin inhibitors, or rituximab 1

Treatment Response Assessment

• Complete response: Proteinuria <0.5 g/g and stable/improved kidney function

• Partial response: ≥50% reduction in proteinuria to <3 g/g and stable/improved kidney function

• No response: Failure to achieve partial or complete response within 6-12 months 2

• Response should be achieved preferably by 6 months but no later than 12 months 1

Maintenance Therapy

• After improvement with initial treatment:
  • Continue MPAA at lower dose (1.5-2 g/day) or azathioprine (2 mg/kg/day)
  • Low-dose prednisone (5-7.5 mg/day)
  • Continue for at least 3 years 1, 2

Special Considerations

• Patients with adverse prognostic factors (acute renal function deterioration, cellular crescents, fibrinoid necrosis):

  • Higher-dose cyclophosphamide may be considered (0.75-1 g/m² monthly for 6 months) 1

• Pregnancy planning:

  • Delay until disease inactive for ≥6 months
  • Safe medications: hydroxychloroquine, glucocorticoids, azathioprine, tacrolimus, cyclosporine
  • Start low-dose aspirin before 16 weeks gestation 2

• Azathioprine considerations:

  • May be used as alternative when MPAA/cyclophosphamide contraindicated or unavailable
  • Associated with higher flare risk 1

Common Pitfalls to Avoid

• Delaying kidney biopsy
• Inadequate immunosuppression
• Rapid glucocorticoid tapering
• Discontinuing hydroxychloroquine
• Premature discontinuation of maintenance therapy (should continue ≥36 months)
• Ignoring non-immune risk factors for CKD progression 2

Monitoring

• Regular assessment of:
  • Renal function and proteinuria
  • Complement levels and anti-dsDNA antibody levels
  • Complete blood count
  • Blood pressure (target <130/80 mmHg) 2

Recent evidence supports using lower initial oral glucocorticoid doses following IV pulse therapy, as this approach demonstrates similar efficacy with fewer serious adverse events compared to traditional high-dose regimens 3.