What is the recommended treatment for frequently relapsing minimal change disease in adults?

Treatment of Frequently Relapsing Minimal Change Disease in Adults

For adults with frequently relapsing minimal change disease (MCD), cyclophosphamide, rituximab, calcineurin inhibitors (CNIs), or mycophenolic acid analogs should be used as steroid-sparing agents to maintain remission and prevent further relapses. 1

First-Line Treatment Options

Cyclophosphamide

• Traditional first-line steroid-sparing agent for frequently relapsing MCD
• Dosage: 2.0-2.5 mg/kg/day for 8-12 weeks 1
• Effective in inducing longer remissions in frequently relapsing patients 1
• Consider when other options are unavailable or contraindicated

Calcineurin Inhibitors (CNIs)

• Cyclosporine: 3-5 mg/kg/day in divided doses 1
• Target blood levels: 80-120 ng/ml 1
• Continue for at least 12 months after remission, followed by slow taper 1
• Relapses are common (up to 80%) after discontinuation 1
• Consider as first option in patients with contraindications to steroids 1

Rituximab

• Emerging as an effective option with fewer side effects
• Significantly reduces relapse rate (from 4 to 0.4/year in one study) 2
• Dosing: 375 mg/m² (either as single dose or multiple doses)
• Extended protocol of 375 mg/m² every three weeks for 3 doses has shown effectiveness 3
• May allow complete withdrawal of steroids and other immunosuppressants 3
• Patients treated with rituximab may be less likely to require change of therapy 4

Mycophenolate Mofetil (MMF)

• Dosage: 500-1000 mg twice daily for 1-2 years 1
• Consider for patients intolerant of steroids, cyclophosphamide, and CNIs 1
• Less evidence compared to other options but included in recent guidelines 1

Treatment Algorithm

1. Initial Assessment:

   • Confirm diagnosis with kidney biopsy if not previously done
   • Define "frequently relapsing" (≥2 relapses within 6 months)
   • Evaluate for contraindications to specific therapies

2. Selection of Steroid-Sparing Agent:

   • First choice: Consider rituximab if available, especially in younger patients who wish to preserve fertility
   • Alternative options:
     • Cyclosporine or tacrolimus if rapid remission needed or rituximab unavailable
     • Cyclophosphamide if cost is a concern and fertility preservation not an issue
     • MMF for patients intolerant to other options

3. Monitoring and Follow-up:

   • Monitor for complete remission (proteinuria <0.3 g/day)
   • Regular assessment of kidney function
   • Monitor drug-specific adverse effects
   • Taper steroids once remission achieved

4. Management of Subsequent Relapses:

   • For rituximab: re-treatment typically effective 2
   • For CNIs: increase dose temporarily until remission, then taper 1
   • Consider switching to alternative agent if frequent relapses continue

Important Considerations

• Long-term prognosis: Overall excellent with <5% progression to end-stage renal disease 5

• Fertility concerns: Avoid cyclophosphamide in patients wishing to preserve fertility 1

• Duration of therapy:

  • Cyclophosphamide: typically 8-12 weeks
  • CNIs: at least 12 months after remission 1
  • MMF: 1-2 years 1

• Common pitfalls:

  • Too rapid tapering of immunosuppression
  • Inadequate duration of therapy
  • Failure to monitor for drug-specific toxicities
  • Not considering patient-specific factors (age, fertility concerns, comorbidities)

Emerging Evidence

Recent studies suggest tacrolimus monotherapy may be an effective alternative for patients wishing to avoid steroids 6. Extended rituximab protocols (multiple doses) appear to be effective in maintaining longer remissions and reducing steroid exposure 3.

The 2021 KDIGO guidelines now include rituximab and mycophenolic acid analogs as recommended options for frequently relapsing/steroid-dependent MCD, expanding treatment options beyond the traditional cyclophosphamide and CNIs 1.