What is the recurrence rate of minimal change disease (MCD) and how is it managed?

Minimal Change Disease Recurrence Rate

More than half of all patients with minimal change disease who initially respond to steroids will experience relapses, with recurrence rates ranging from 34% to 85% in adults and up to 71% in children. 1

Recurrence Rates by Population

Adults

• 34% to 85% of adult patients experience at least one relapse after achieving initial remission 2, 3
• Using life-table analysis, approximately 84% remain in remission at 6 months, 75% at 1 year, and 63% during extended follow-up 3
• Younger adults (under 30-45 years) have significantly higher relapse rates compared to older patients 3, 4
• Relapses most commonly occur within the first 6-12 months after achieving remission 2

Children

• Up to 71% of pediatric patients experience relapses after initial steroid-induced remission 2
• Children under 5 years have the highest incidence of MCD (90% of nephrotic syndrome cases) and correspondingly high relapse rates 1

Risk Factors for Relapse

Key predictors that increase relapse risk include: 4

• Younger age at disease onset (most consistent predictor across studies)
• More severe nephrotic features at presentation:
  • Lower serum albumin levels
  • Higher cholesterol levels
• Shorter initial treatment duration (less than 12 weeks of corticosteroids)
• Lower grade of mesangial proliferation on biopsy (paradoxically protective)
• Monotherapy with corticosteroids alone versus combined treatment with cyclophosphamide

Patterns of Relapse

Frequent Relapsers and Steroid Dependency

• More than 50% of relapsing patients become frequent relapsers (≥2 relapses within 6 months) or steroid-dependent 1
• Those who relapse frequently have greater risk of becoming steroid-dependent, defined as two consecutive relapses during therapy or within 14 days of completing steroids 1
• Up to 40% of patients develop a frequent relapsing/steroid-dependent course requiring alternative immunosuppression 5

Secondary Steroid Resistance

• A very small subset of initially steroid-sensitive patients develop secondary steroid resistance, which carries a poor prognosis with potential progression to end-stage renal disease 5
• This represents a distinct clinical entity from primary steroid resistance

Management of Relapses

First Relapse

Restart the same corticosteroid regimen that induced initial remission: 1

• Prednisone 1 mg/kg/day (maximum 80 mg) or 2 mg/kg alternate-day (maximum 120 mg)
• Maintain high-dose for minimum 4 weeks if remission achieved
• Taper slowly over 6 months total treatment duration

Frequent Relapses or Steroid Dependency

Steroid-sparing agents are indicated to avoid cumulative corticosteroid toxicity: 1

First-line steroid-sparing options:

1. Cyclophosphamide (CYC):

   • Dose: 2.0-2.5 mg/kg/day for 8-12 weeks in adults 1
   • Achieves longer remissions in frequently relapsing patients compared to steroid-dependent patients 1
   • Combined initial treatment with corticosteroids plus cyclophosphamide reduces relapse frequency 4
   • Major limitation: cumulative gonadal toxicity and oncogenicity risk 1

2. Calcineurin Inhibitors (CNIs):

   • Cyclosporine: 3-5 mg/kg/day in divided doses, target trough 60-150 ng/mL 1
   • Tacrolimus: 0.05-0.1 mg/kg/day in divided doses, target trough 5-10 ng/mL 1
   • Complete remission achieved in 73-82% of steroid-dependent adults 1
   • Continue for at least 12 months, then taper slowly 1
   • Critical pitfall: "CNI dependency" - rapid relapse upon discontinuation occurs frequently 1
   • Longer uninterrupted treatment duration (27 months vs 7 months) and gradual tapering reduce CNI dependency 1
   • Low-dose maintenance (1-3 mg/kg/day cyclosporine) can maintain remission long-term 1

3. Rituximab:

   • Emerging as effective option providing long-term remission off-therapy in some patients 6
   • Particularly useful for patients wishing to avoid fertility complications from cyclophosphamide 1

4. Mycophenolate Mofetil (MMF):

   • Dose: 500-1000 mg twice daily for 1-2 years 1
   • Reserved for patients intolerant of corticosteroids, cyclophosphamide, and CNIs 1
   • Evidence quality is lower compared to other agents 1

Monitoring During Long-Term Therapy

For patients on CNIs beyond 12 months: 1

• Monitor serum creatinine closely - discontinue if creatinine rises >30% above baseline and doesn't plateau after dose reduction
• Consider repeat renal biopsy at 12-24 months to assess for CNI nephrotoxicity, especially if creatinine elevated or maintenance dose >3.5 mg/kg/day 1
• Specify exact brand of cyclosporine to avoid bioavailability variations from brand switching 1

Prognosis Despite Relapses

The long-term renal prognosis remains excellent: 2, 4

• Fewer than 5% progress to end-stage renal disease 2, 4
• Patient survival is 83-98% at 15 years 2
• Forms that respond to steroids usually do not lead to chronic renal damage, unlike steroid-resistant forms which may represent unrecognized FSGS 6

However, the morbidity from recurrent disease is substantial due to repeated immunosuppression requirements and cumulative drug toxicity 6