What is the initial management for lupus nephritis?

Initial Management of Lupus Nephritis

The initial management for lupus nephritis should include glucocorticoids plus mycophenolic acid analogs (MPAA) as first-line therapy, with the addition of belimumab or calcineurin inhibitors as effective options for improving outcomes and reducing mortality. 1, 2

Diagnostic Approach

• Renal biopsy is essential before initiating treatment when there is:

  • Reproducible proteinuria ≥0.5 g/24h
  • Unexplained decrease in GFR
  • Active urinary sediment

• Pathological assessment using the ISN/RPS 2003 classification system helps determine treatment approach 1

Initial Treatment Algorithm

Step 1: Determine Lupus Nephritis Class

• Class III or IV (±V): Proliferative lupus nephritis - requires aggressive immunosuppression
• Pure Class V: Membranous lupus nephritis with nephrotic-range proteinuria
• Class II with proteinuria >1g/24h: Less aggressive approach

Step 2: Initial Immunosuppressive Regimen for Class III/IV (±V)

1. Glucocorticoids:

   • IV methylprednisolone pulses (500-750 mg daily for 3 days)
   • Followed by oral prednisone (0.5-0.6 mg/kg/day, maximum 40 mg)
   • Taper to ≤10 mg/day by 4-6 months 1

2. Plus one of the following:

   • MPAA (first choice): Mycophenolate mofetil 2-3 g/day divided in two doses 1
   • Low-dose IV cyclophosphamide: 500 mg every 2 weeks for 6 doses (total 3g) 1
   • MPAA + calcineurin inhibitor (when eGFR >45 ml/min/1.73m²) 1
   • Belimumab + MPAA or cyclophosphamide: Particularly beneficial for patients with high risk of progression 1, 3

Step 3: Adjunctive Treatments

• Hydroxychloroquine: Should be included in all treatment regimens unless contraindicated 2
• RAAS blockade (ACE inhibitors or ARBs): For proteinuria >500 mg/day or hypertension 1, 2
• Blood pressure control: Target <130/80 mmHg 2

Special Considerations

For Patients with Adverse Prognostic Factors

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

Consider higher-dose cyclophosphamide regimen (0.75-1 g/m² monthly for 6 months) 1

For Patients at High Risk of Infertility

• Prefer MPAA-based regimens over cyclophosphamide 1
• Consider fertility preservation before initiating cyclophosphamide 2

For Pure Class V Lupus Nephritis

• MPAA (MMF 3 g/day) with oral prednisone is recommended as first-line therapy 1
• Calcineurin inhibitors are effective alternatives 1

Monitoring Response

• Regular assessment of:

  • Renal function (serum creatinine, eGFR)
  • Proteinuria
  • Urinary sediment
  • Complement levels
  • Anti-dsDNA antibody levels

• Treatment goals:

  • Complete response: Proteinuria <0.5 g/g and normal/near-normal renal function
  • Partial response: ≥50% reduction in proteinuria to subnephrotic levels and stable renal function
  • Target achievement by 6-12 months 1

Common Pitfalls to Avoid

1. Delaying kidney biopsy
2. Inadequate immunosuppression
3. Rapid glucocorticoid tapering
4. Discontinuing hydroxychloroquine
5. Using azathioprine as initial therapy (associated with higher flare risk) 1
6. Premature discontinuation of maintenance therapy 2

Subsequent Treatment

After achieving response with initial therapy, transition to maintenance therapy with:

• MPAA at lower dose (1.5-2 g/day) or azathioprine (2 mg/kg/day) if MPAA is not tolerated
• Low-dose prednisone (5-7.5 mg/day)
• Continue for at least 3 years 1

Recent evidence suggests that lower initial oral glucocorticoid doses (≤0.5 mg/kg/day) following IV pulse therapy are as effective as higher doses (1.0 mg/kg/day) but with significantly fewer serious adverse events 4, supporting the trend toward glucocorticoid-sparing regimens.