What is the management of nephrotic syndrome?

Management of Nephrotic Syndrome

The management of nephrotic syndrome should begin with corticosteroid therapy as first-line treatment, with prednisone given at 60 mg/m²/day (maximum 60 mg) as a single daily dose for 6 weeks, followed by 40 mg/m²/day (maximum 40 mg) on alternate days for 6 weeks with subsequent tapering. 1

Initial Corticosteroid Treatment

First Episode Management

• Dosage: Oral prednisone 60 mg/m²/day (maximum 60 mg) as a single daily dose
• Duration: 6 weeks of daily therapy
• Follow-up regimen: 40 mg/m²/day (maximum 40 mg) on alternate days for 6 weeks
• Tapering: Reduce by 10 mg/m² per week to 5 mg on alternate days for a total treatment duration of 16 weeks 1

Definition of Remission

• Trace/negative protein on urine dipstick for at least 3 consecutive days 1

Management of Relapses

Treatment Protocol for Relapses

• Dosage: Oral prednisone 60 mg/m²/day (maximum 60 mg) daily until remission
• After remission: Decrease to 40 mg/m²/day (maximum 40 mg) on alternate days for 1 week
• Tapering: Reduce by 10 mg/m² per week to complete a total of 4 weeks of treatment 1

Frequently Relapsing (FR) or Steroid-Dependent (SD) Nephrotic Syndrome

• Maintain on lowest possible alternate-day prednisone dose to prevent relapses while minimizing adverse effects 1
• Consider daily prednisone at lowest effective dose if alternate-day therapy is ineffective 1
• During upper respiratory infections, increase to daily prednisone to prevent relapse in patients already on alternate-day therapy 1

Steroid-Sparing Agents

When patients develop frequently relapsing or steroid-dependent nephrotic syndrome, steroid-sparing agents should be considered to reduce steroid-related toxicity:

First-Line Steroid-Sparing Agent

• Levamisole: 2.5 mg/kg on alternate days for 12-24 months 1
  • Monitor white blood cell count monthly for neutropenia
  • Preferred due to cost-effectiveness and favorable safety profile

Second-Line Options

1. Cyclophosphamide:

   • Oral dosage: 2 mg/kg/day for 8-12 weeks (maximum cumulative dose 168 mg/kg) 1, 2
   • IV alternative: 500 mg/m² monthly for 4 months 1
   • Monitoring: Regular complete blood counts
   • Caution: Risk of gonadal toxicity, especially with cumulative doses >200 mg/kg 3

2. Calcineurin Inhibitors:

   • Cyclosporine: 3-5 mg/kg/day divided into 2 doses for 6-24 months 1
   • Tacrolimus: 0.1-0.2 mg/kg/day divided into 2 doses 1
   • Monitoring: Drug levels, renal function, blood pressure
   • Target trough levels: 50-100 ng/ml for cyclosporine 1

3. Mycophenolate Mofetil:

   • Dosage: 600-1200 mg/m²/day divided into 2 doses for 6-24 months 1
   • Monitoring: Complete blood count every 4 weeks

Steroid-Resistant Nephrotic Syndrome

For patients who fail to respond to initial steroid therapy:

1. Kidney biopsy is indicated to determine histological subtype
2. Calcineurin inhibitors are the preferred treatment option 1
3. If CNIs are not available, consider cyclophosphamide 1

Supportive Care Measures

• Fluid management: Restrict fluid intake during edematous phase
• Sodium restriction: Limit dietary sodium intake
• Diuretics: Consider loop diuretics for significant edema
• Thromboprophylaxis: Consider in severe cases with hypoalbuminemia
• Infection prevention: Monitor for and promptly treat infections

Special Considerations

Adult Nephrotic Syndrome

• Adult patients may require longer treatment courses (up to 16 weeks) to achieve remission 4
• Response to steroids may take longer in adults compared to children (up to 16 weeks vs. 11 days) 3

Monitoring for Complications

• Short-term: Hypovolemia, acute kidney injury, infections, thrombosis
• Long-term: Growth retardation, hypertension, cataracts, osteoporosis, diabetes

Common Pitfalls and Caveats

1. Inadequate initial steroid duration: Ensure complete 12-16 week course for first episode
2. Rapid steroid tapering: Follow recommended tapering schedule to prevent early relapse
3. Delayed introduction of steroid-sparing agents: Consider early in frequently relapsing cases
4. Overlooking infections: Infections can trigger relapses; monitor and treat promptly
5. Inadequate monitoring of drug toxicity: Regular monitoring of side effects is essential for all immunosuppressive agents

The management approach should be adjusted based on response to therapy, with the goal of maintaining remission while minimizing medication-related adverse effects to improve long-term morbidity, mortality, and quality of life outcomes.