What is the initial treatment for a patient with Systemic Lupus Erythematosus (SLE) and a kidney biopsy showing glomerulonephritis?

Initial Treatment for SLE with Glomerulonephritis

For patients with SLE and kidney biopsy showing glomerulonephritis, the initial treatment should be glucocorticoids plus mycophenolic acid analogs (MPAA) as this combination has the best efficacy/toxicity ratio for preserving kidney function and reducing mortality. 1

Treatment Algorithm Based on Biopsy Findings

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

1. Initial Immunosuppressive Therapy:

   • Glucocorticoids plus ONE of the following options 1:
     • Mycophenolic acid analogs (MPAA) - preferred first-line option
     • Low-dose intravenous cyclophosphamide
     • Belimumab with either MPAA or low-dose cyclophosphamide
     • MPAA with calcineurin inhibitor (if eGFR >45 ml/min/1.73m²)

2. Glucocorticoid Regimen 1:

   • Initial: IV methylprednisolone pulses (250-500mg/day for up to 3 days)
   • Followed by oral prednisone:
     • Weeks 0-2: 0.5-0.6 mg/kg/day (max 40 mg)
     • Weeks 3-4: 0.3-0.4 mg/kg/day
     • Progressive tapering to ≤7.5 mg/day within 3-6 months

3. MPAA Dosing:

   • Mycophenolate mofetil: Target dose 2-3 g/day divided into 2 doses 1, 2
   • Adjust based on body weight and renal function

Patient-Specific Considerations

Special Situations Affecting Treatment Choice:

• Poor medication adherence: Consider IV cyclophosphamide 1
• Fertility concerns: Prefer MPAA over cyclophosphamide 1
• Nephrotic-range proteinuria with preserved kidney function: Consider adding calcineurin inhibitor 1
• Repeated kidney flares or high risk of progression: Consider triple therapy with belimumab, glucocorticoids, and either MPAA or cyclophosphamide 1

Adjunctive Therapies

All patients should receive 1:

• Hydroxychloroquine (unless contraindicated)
• Infection prophylaxis (assess for TB, screen for HBV, HCV, HIV)
• Bone protection (calcium, vitamin D, consider bisphosphonates)
• Sun protection (sunscreen, limit UV exposure)
• Fertility preservation measures when appropriate

Treatment Goals and Monitoring

• Target outcomes: Complete renal response (proteinuria <0.5g/24h with normal or near-normal renal function) 1
• Timeline: Aim for partial response by 6 months and complete response by 12 months 2
• Monitoring parameters:
  • Proteinuria (goal: 25% reduction at 3 months, 50% at 6 months)
  • Renal function
  • Serological markers (complement levels, anti-dsDNA)

Important Caveats

• Maintenance therapy: After initial response, continue with MPAA for at least 3 years 1
• Treatment failures: If no response to MPAA, switch to cyclophosphamide or vice versa; rituximab may be considered for refractory cases 1
• Pregnancy planning: Medications should be adjusted without reducing treatment intensity 1
• Lifetime cyclophosphamide exposure: Should be limited to <36g to minimize cancer risk 1

Pitfalls to Avoid

1. Delaying treatment while awaiting biopsy results in patients with clear clinical signs of nephritis
2. Excessive glucocorticoid exposure leading to unnecessary adverse effects
3. Inadequate duration of maintenance therapy increasing risk of flares
4. Overlooking adjunctive therapies that can prevent complications
5. Failing to monitor for drug toxicities and adjust doses accordingly

The 2024 KDIGO guidelines provide the most current evidence-based approach to managing lupus nephritis, emphasizing the importance of early aggressive therapy to preserve kidney function and improve long-term outcomes 1.