What is the initial management for acute nephrotic syndrome?

Acute Nephrotic Syndrome Management

Begin immediate corticosteroid therapy with prednisone 60 mg/m²/day (maximum 60 mg) as a single daily dose for children, or 1 mg/kg/day (maximum 80 mg) for adults, while simultaneously implementing supportive measures including sodium restriction, loop diuretics for edema, and infection prevention strategies. 1, 2

Immediate Supportive Care

Edema Management:

• Administer loop diuretics (furosemide) as first-line therapy for severe edema and anasarca 1, 3
• Restrict dietary sodium to <2.0 g/day to reduce fluid retention 1, 3
• Avoid routine intravenous albumin infusions; reserve only for clinical indicators of hypovolemia (hypotension, tachycardia, poor perfusion), not based on serum albumin levels alone 1
• Do not administer intravenous saline, which worsens edema 1

Blood Pressure and Proteinuria Control:

• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria reduction and blood pressure control 3
• Target systolic blood pressure <120 mmHg in adults using standardized office measurement 3

Corticosteroid Therapy Protocol

For Children (>1 year old):

• Start prednisone 60 mg/m²/day (maximum 60 mg) as a single daily dose for 4-6 weeks 4, 1, 5
• After 4-6 weeks, transition to alternate-day dosing at 40 mg/m² per dose (maximum 40 mg on alternate days) for 2-5 months with gradual tapering 4
• Total initial treatment duration should be at least 12 weeks, with evidence supporting up to 6 months for reduced relapse rates 4

Important dosing consideration: Prednisone dosed at 2 mg/kg/day is NOT equivalent to 60 mg/m²/day in children weighing <30 kg, with the weight-based dosing providing approximately 15% less medication 6. Use body surface area calculation for accuracy 6.

For Adults:

• 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 minimum 4 weeks if complete remission achieved 1, 2
• If no remission, continue up to 16 weeks before declaring steroid resistance 1, 2
• After achieving remission, taper slowly over 6 months 2, 3

Alternative First-Line Therapy

When corticosteroids are contraindicated or not tolerated:

• Consider calcineurin inhibitors (CNIs) as first-line therapy for patients with uncontrolled diabetes mellitus, severe psychiatric conditions, severe osteoporosis, or morbid obesity with elevated HbA1c 1, 3
• Cyclosporine: 3-5 mg/kg/day in divided doses 1, 3
• Tacrolimus: 0.05-0.1 mg/kg/day in divided doses (adults) or 0.1-0.2 mg/kg/day (children) 1, 3

Infection Prevention (Critical Priority)

Vaccination:

• Administer pneumococcal vaccination (23-valent or conjugate vaccine) before or early in immunosuppressive therapy 1, 2
• Give annual influenza vaccination to patients and household contacts 1, 2
• Avoid live vaccines in children receiving immunosuppressive agents 2

Prophylaxis:

• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 3

Monitoring During Initial Treatment

Proteinuria Assessment:

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio 1, 3
• Complete remission defined as: urine protein <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 1

Treatment Response:

• Regularly assess proteinuria and kidney function to evaluate treatment response 2, 3
• Monitor for medication side effects, particularly with long-term immunosuppressive therapy 2, 3

Biopsy Considerations

Children:

• Defer kidney biopsy if typical presentation and response to initial steroid therapy within 4-6 weeks 2, 3
• Perform biopsy if steroid-resistant after 8 weeks of adequate therapy 2, 3

Adults:

• Kidney biopsy generally indicated before initiating immunosuppressive therapy 2, 3
• Exception: Positive serum anti-phospholipase A2 receptor antibodies are diagnostic of membranous nephropathy, eliminating need for biopsy 7

Critical Pitfalls to Avoid

Do not declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy completed 1, 2. Many patients show partial response that continues to improve through 16 weeks 1.

Do not stop therapy prematurely if partial response occurring—continue up to 16 weeks 1.

Do not use low-dose daily or alternate-day maintenance corticosteroids for steroid-dependent nephrotic syndrome when second-line agents (alkylating agents, levamisole, CNIs, or mycophenolate mofetil) are available, as these have higher quality evidence for efficacy 4.

Management of Relapse

For infrequent relapses:

• Treat with prednisone 60 mg/m² or 2 mg/kg (maximum 60 mg/day) until remission for at least 3 days 4
• Follow with alternate-day prednisone (40 mg/m² per dose) for at least 4 weeks 4

For frequently relapsing or steroid-dependent disease:

• Treat relapses with daily prednisone until remission for at least 3 days, followed by alternate-day prednisone for at least 3 months 4
• Consider steroid-sparing agents: alkylating agents (cyclophosphamide 2 mg/kg/day for 8-12 weeks), levamisole (2.5 mg/kg on alternate days for at least 12 months), calcineurin inhibitors, or mycophenolate mofetil 4, 3