What is the initial treatment for lupus nephritis?

Initial Treatment for Lupus Nephritis

For patients with active Class III or IV lupus nephritis, initial treatment should consist of glucocorticoids plus mycophenolic acid analogs (MPAA) or low-dose intravenous cyclophosphamide, as these regimens have the best efficacy/toxicity ratio for preserving renal function and improving survival. 1

Diagnostic Approach Before Treatment

• Renal biopsy is essential before initiating treatment
• International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system should guide therapy
• Clinical and laboratory tests alone cannot accurately predict histological findings 1

Induction Therapy Options

1. First-line options:

   • Mycophenolic acid analogs (MMF target dose: 3 g/day for 6 months) plus glucocorticoids 1
   • Low-dose intravenous cyclophosphamide (total dose 3 g over 3 months) plus glucocorticoids 1

2. Alternative options:

   • Belimumab plus either MPAA or low-dose IV cyclophosphamide plus glucocorticoids 1
   • MPAA plus calcineurin inhibitor (when eGFR >45 ml/min/1.73 m²) plus glucocorticoids 1
   • Azathioprine may be considered when MPAA or cyclophosphamide are contraindicated, not tolerated, or unavailable (note: higher flare risk) 1

Glucocorticoid Regimen

• Begin with IV methylprednisolone pulses (500-750 mg for 3 consecutive days)
• Follow with oral prednisone 0.5 mg/kg/day for 4 weeks
• Taper to ≤10 mg/day by 4-6 months
• Consider reduced-dose regimens when kidney and extrarenal manifestations show improvement 1

Important Adjunctive Therapies

• Hydroxychloroquine for all SLE patients to reduce flares and improve outcomes 1
• ACE inhibitors or ARBs for patients with proteinuria or hypertension
• Statins for persistent dyslipidemia
• Calcium and vitamin D supplementation
• Appropriate non-live vaccinations 1

Treatment Goals and Monitoring

• Aim for complete renal response (proteinuria <50 mg/mol and normal/near-normal renal function)
• Target partial response by 6 months and complete response by 12 months
• Regular monitoring of:
  • Serum creatinine and eGFR
  • Proteinuria
  • Urinary sediment
  • Complement levels (C3, C4)
  • Anti-dsDNA antibody levels
  • Complete blood count
  • Blood pressure 1

Special Considerations

• Patients with adverse prognostic factors (acute deterioration in renal function, substantial cellular crescents, fibrinoid necrosis) may benefit from higher-dose cyclophosphamide regimens 1
• Patients at high risk of infertility should preferentially receive MPAA-based therapy rather than cyclophosphamide 1
• Patients with adherence concerns may benefit from intravenous cyclophosphamide 1

Historical Context and Evolution of Treatment

While cyclophosphamide with high-dose corticosteroids was historically considered the gold standard treatment for lupus nephritis 2, 3, current guidelines favor either MPAA or low-dose cyclophosphamide with glucocorticoids as they offer improved efficacy-to-toxicity ratios 1. This shift reflects the evolving treatment goals from merely improving survival to also minimizing treatment-related toxicity while maintaining efficacy 2.

Common Pitfalls to Avoid

1. Delaying renal biopsy before treatment initiation
2. Using clinical parameters alone to guide therapy without histological confirmation
3. Failing to adjust glucocorticoid doses downward when improvement occurs
4. Neglecting adjunctive therapies like hydroxychloroquine and ACE inhibitors/ARBs
5. Inadequate monitoring for treatment response and potential toxicities
6. Not considering maintenance therapy after successful induction