What is the initial treatment for lupus nephritis class 4?

Initial Treatment for Lupus Nephritis Class IV

For patients with class IV lupus nephritis, the recommended initial treatment is mycophenolic acid (MPA) (mycophenolate mofetil [MMF] target dose: 2-3 g/day for 6 months) or low-dose intravenous cyclophosphamide (total dose 3 g over 3 months) in combination with glucocorticoids, as they have the best efficacy/toxicity ratio. 1

First-Line Treatment Options

Immunosuppressive Agents:

• Mycophenolic acid (MPA):

  • MMF target dose: 2-3 g/day for 6 months 1
  • MPA sodium at equivalent dose 1
  • Preferred for patients at high risk for infertility or with prior cyclophosphamide exposure 1

• Intravenous Cyclophosphamide (CY):

  • Low-dose regimen: 500 mg every 2 weeks for a total of 6 doses (total 3 g over 3 months) 1
  • Alternative dosing: monthly at higher doses (0.75-1 g/m² for 6 months) for patients with adverse prognostic factors 1
  • Can be considered for patients who may have difficulty adhering to an oral regimen 1

Glucocorticoid Regimen:

• Initial treatment should include three consecutive pulses of intravenous methylprednisolone (500-750 mg each) 1
• Followed by oral prednisone 0.3-0.5 mg/kg/day for up to 4 weeks 1
• Taper to ≤7.5 mg/day by 3-6 months 1

Alternative Treatment Options

• Combination therapy with MMF (target dose: 1-2 g/day) plus a calcineurin inhibitor (especially tacrolimus) is an alternative, particularly effective for patients with nephrotic-range proteinuria 1

• High-dose intravenous cyclophosphamide (0.5-0.75 g/m² monthly for 6 months) can be considered for patients at high risk for kidney failure, defined by:

  • Reduced GFR
  • Histological presence of crescents or fibrinoid necrosis
  • Severe interstitial inflammation 1

• Triple immunosuppressive regimen including belimumab with glucocorticoids and either MPAA or reduced-dose cyclophosphamide may be considered for patients with repeated kidney flares or at high risk for progression to kidney failure 1

Adjunctive Therapy

• Hydroxychloroquine should be co-administered (dose not to exceed 5 mg/kg/day and adjusted for GFR) 1

• Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are recommended for all patients with UPCR >500 mg/g or arterial hypertension 1

• Statins are recommended based on lipid levels and estimated 10-year cardiovascular disease risk 1

Treatment Goals and Monitoring

• Treatment aims for preservation or improvement of kidney function with:

  • Reduction in proteinuria of at least 25% by 3 months
  • 50% reduction by 6 months
  • UPCR target below 500-700 mg/g by 12 months (complete clinical response) 1

• Patients with nephrotic-range proteinuria at baseline may require an additional 6-12 months to reach complete clinical response 1

Subsequent Treatment (Maintenance)

After achieving improvement with initial therapy:

• Continue with MMF at lower doses (1-2 g/day) or switch to azathioprine (2 mg/kg/day) if pregnancy is contemplated 1
• Maintain low-dose prednisone (2.5-5 mg/day) when needed to control disease activity 1
• Continue maintenance therapy for at least 3-5 years 1

Important Considerations

• Renal biopsy is essential before initiating treatment as it guides therapy decisions 1

• Treatment failure: If there is inadequate response to initial therapy, consider:

  • Switching from MPA to cyclophosphamide or vice versa
  • Adding rituximab 1
  • Assessing adherence to treatment and therapeutic drug monitoring 1

• Pregnancy planning: Patients who plan to conceive should switch from MMF to azathioprine at least 3 months prior to conception 1

• Long-term outcomes: Complete or partial renal response has significant positive prognostic value for both kidney and patient survival 2