Initial Management of Nephrotic Syndrome
Begin with sodium restriction (<2.0 g/day), loop diuretics for edema, and ACE inhibitors/ARBs at maximally tolerated doses, while simultaneously initiating corticosteroid therapy with prednisone 1 mg/kg/day (maximum 80 mg) for adults or 60 mg/m²/day (maximum 80 mg) for children, continuing for at least 4 weeks before assessing response. 1, 2, 3
Immediate Supportive Management
Fluid and Edema Control
- Restrict dietary sodium to <2.0 g/day as the foundation of edema management 1, 2
- Administer loop diuretics (furosemide) as first-line agents for managing edema and anasarca 1, 2
- Avoid routine intravenous albumin infusions; use only when clinical indicators of hypovolemia are present (hypotension, tachycardia, poor perfusion), not based on serum albumin levels alone 2
- Avoid intravenous saline administration, which worsens edema 2
Blood Pressure and Proteinuria Management
- Initiate ACE inhibitors or ARBs at maximally tolerated doses for both proteinuria reduction and blood pressure control 1
- Target systolic blood pressure <120 mmHg in adults using standardized office BP measurement 1
Diagnostic Workup Before Treatment
Essential Investigations
- Confirm nephrotic-range proteinuria with 24-hour urine collection or spot urine protein-to-creatinine ratio 1, 3
- Exclude secondary causes including diabetes mellitus, systemic lupus erythematosus, infections, and medication review 1, 3
Kidney Biopsy Indications
- In adults, perform kidney biopsy before initiating immunosuppressive therapy 3
- In children with typical presentation (age 1-10 years, no hematuria, normal complement, normal blood pressure), defer biopsy if there is response to initial steroid therapy 1, 3
- Perform biopsy in steroid-resistant nephrotic syndrome in children after 8 weeks of adequate corticosteroid therapy 1, 3
Corticosteroid Therapy Protocol
Adults
- Administer prednisone 1 mg/kg/day (maximum 80 mg) as a single daily dose, or alternate-day dosing at 2 mg/kg (maximum 120 mg) 1, 2, 3
- Continue high-dose therapy for a minimum of 4 weeks if complete remission is achieved 2, 3
- Extend treatment up to 16 weeks if remission is not achieved, as response may take longer in adults 1, 3
- After achieving remission, taper steroids slowly over 6 months 1, 3
Children
- Administer prednisone 60 mg/m²/day (maximum 80 mg) as a single daily dose for 4-6 weeks, followed by alternate-day dosing at 40 mg/m² per dose (maximum 40 mg on alternate days) for 2-5 months with gradual tapering 2, 4
- Total initial treatment duration should be at least 12 weeks, with evidence supporting up to 6 months for reduced relapse rates 2
Critical Pitfall: Do not use 2 mg/kg/day dosing interchangeably with 60 mg/m²/day in children weighing <30 kg, as the weight-based dose is significantly lower and may lead to treatment failure 5
Alternative First-Line Therapy
When to Use Calcineurin Inhibitors Instead of Corticosteroids
Consider calcineurin inhibitors (CNIs) as first-line therapy for patients with relative contraindications or intolerance to high-dose corticosteroids, including: 1, 2
- Uncontrolled diabetes mellitus
- Severe psychiatric conditions
- Severe osteoporosis
- Morbid obesity with elevated HbA1c
CNI Dosing
- Cyclosporine: 3-5 mg/kg/day divided into 2 doses 1, 2
- Tacrolimus: 0.1-0.2 mg/kg/day divided into 2 doses (children) or 0.05-0.1 mg/kg/day (adults) 1, 2
Infection Prevention (Critical Priority)
Vaccination
- Administer pneumococcal vaccination (23-valent or conjugate vaccine) before or early in immunosuppressive therapy 2, 3
- Give annual influenza vaccination to patients and household contacts 2, 3
- Live vaccines are contraindicated in children receiving immunosuppressive agents 3
Prophylactic Antibiotics
- Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 1
Monitoring Treatment Response
Proteinuria Assessment
- Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio to assess treatment response 2
- Complete remission is defined as: urine protein <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 2
Kidney Function
- Regularly assess proteinuria and kidney function to evaluate treatment response 1, 3
- Monitor for medication side effects, particularly with long-term immunosuppressive therapy 1, 3
Management of Steroid Resistance
Defining Steroid Resistance
Do not declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy has been completed 2, 3
Second-Line Treatment
- For steroid-resistant cases, initiate calcineurin inhibitors (CNIs) 3
- Continue CNI therapy for a minimum of 6 months, then stop if remission is not achieved 3
- If at least partial remission is achieved by 6 months, continue CNIs for a minimum of 12 months 3
Special Considerations
Relapsing Disease
- For infrequent relapses, treat with prednisone 60 mg/m² or 2 mg/kg (maximum 60 mg/day) until remission for at least 3 days, followed by alternate-day prednisone (40 mg/m² per dose) for at least 4 weeks 2
- For frequently relapsing or steroid-dependent disease, consider steroid-sparing agents such as cyclophosphamide, levamisole, calcineurin inhibitors, or mycophenolate mofetil 1, 2