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 as clinical and laboratory tests cannot accurately predict histological findings 1
• Use the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system to guide therapy 1
• Treatment decisions should be based on lupus nephritis class:
  • Class III (focal) or IV (diffuse) proliferative nephritis requires aggressive immunosuppression
  • Class V (membranous) with nephrotic proteinuria requires specific treatment approaches
  • Mixed classes (III/V or IV/V) should be treated based on the proliferative component

First-Line Treatment Options

For Class III or IV Lupus Nephritis:

1. Induction Therapy (choose one option):

   • 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
   • Belimumab plus either MPAA or low-dose intravenous cyclophosphamide plus glucocorticoids 1
   • MPAA plus calcineurin inhibitor (when eGFR >45 ml/min/1.73 m²) plus glucocorticoids 1

2. Glucocorticoid Regimen:

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

For Pure Class V Nephritis with Nephrotic-Range Proteinuria:

• MMF (target dose 3 g/day) plus oral prednisone (0.5 mg/kg/day) 1
• Alternative options for non-responders: cyclophosphamide, calcineurin inhibitors, or rituximab 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
• Azathioprine may be considered as an alternative when MPAA or cyclophosphamide are contraindicated, not tolerated, or unavailable, but carries a higher flare risk 1

Adjunctive Treatments

• Hydroxychloroquine for all SLE patients (reduces flares and improves outcomes) 1, 2
• ACE inhibitors or ARBs for patients with proteinuria or hypertension 1
• Statins for persistent dyslipidemia 1
• Calcium and vitamin D supplementation 1
• Appropriate vaccinations (non-live vaccines) 1

Treatment Goals and Monitoring

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

Maintenance Therapy

After achieving improvement with initial treatment:

• Continue with MPAA at lower doses (MMF 2 g/day) or azathioprine (2 mg/kg/day) for at least 3 years 1
• Maintain low-dose prednisone (5-7.5 mg/day) 1
• Patients who responded to MPAA should remain on MPAA unless pregnancy is contemplated 1

Common Pitfalls to Avoid

1. Delaying treatment - Prompt diagnosis and treatment initiation are crucial for preserving renal function
2. Inadequate immunosuppression - Underdosing can lead to treatment failure
3. Excessive glucocorticoid exposure - Balance efficacy with minimizing long-term complications
4. Overlooking adjunctive therapies - Hydroxychloroquine, ACE inhibitors/ARBs are essential components
5. Insufficient monitoring - Regular assessment of disease activity and treatment response is necessary
6. Premature discontinuation - Maintenance therapy should continue for at least 3 years

By following this treatment algorithm, clinicians can optimize outcomes for patients with lupus nephritis, focusing on preserving renal function, preventing disease flares, and minimizing treatment-related toxicity.