What is the initial management for a patient with nephrotic syndrome?

Initial Management of Nephrotic Syndrome

The initial management of nephrotic syndrome should include supportive care with sodium restriction, diuretics, and ACE inhibitors/ARBs, followed by corticosteroid therapy with prednisone at 1 mg/kg/day (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg) for idiopathic cases. 1, 2

Diagnostic Confirmation

• Confirm nephrotic-range proteinuria with 24-hour urine collection or spot urine protein-to-creatinine ratio 1
• Perform investigations to exclude secondary causes including diabetes mellitus, systemic lupus erythematosus, infections, and medication review 1
• In children with typical presentation, kidney biopsy may be deferred if there is response to initial steroid therapy 1
• In adults, kidney biopsy is typically indicated for diagnosis to determine the underlying pathology 3

Supportive Management

• Restrict dietary sodium to <2.0 g/day to reduce edema and help manage proteinuria 1
• Use loop diuretics (e.g., furosemide) as first-line agents for edema management 1, 4
• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria and blood pressure control 1
• Target systolic blood pressure <120 mmHg in adults using standardized office BP measurement 1
• Consider ambulatory management when possible to improve quality of life and reduce infection risk 1

Corticosteroid Therapy

For Children:

• Administer prednisone at 60 mg/m² per day (maximum 80 mg/day) or 2 mg/kg/day for 4-6 weeks 2, 5
• Follow with alternate-day prednisone at 40 mg/m² per dose (1.5 mg/kg) for at least 6-8 weeks 5
• Note that dosing by body weight (2 mg/kg/day) may result in lower doses than BSA-based dosing (60 mg/m²/day) for children weighing <30 kg 6

For Adults:

• Administer prednisone at 1 mg/kg/day (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg) 2
• Continue high-dose corticosteroids for a minimum of 4 weeks and up to 16 weeks as tolerated or until complete remission 2
• Taper corticosteroids slowly over a period of 6 months after achieving complete remission 2

Management of Complications

• Administer pneumococcal and influenza vaccines to prevent infections 1
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 1
• Monitor for thromboembolism risk, particularly in patients with membranous nephropathy 3
• Regularly assess proteinuria and kidney function to evaluate treatment response 1
• Monitor for side effects of medications, particularly with long-term immunosuppressive therapy 1

Alternative First-Line Therapy

• Consider calcineurin inhibitors (CNIs) as first-line therapy for patients with relative contraindications or intolerance to high-dose corticosteroids (e.g., uncontrolled diabetes, psychiatric conditions, severe osteoporosis) 2
• For cyclosporine, use 3-5 mg/kg/day divided into 2 doses with monitoring of drug levels 2
• For tacrolimus, use 0.1-0.2 mg/kg/day divided into 2 doses 2

Special Considerations

• Avoid intravenous fluids and saline; concentrate oral fluid intake if necessary 1
• Use albumin infusions based on clinical indicators of hypovolemia, not serum albumin levels 1
• In children with frequently relapsing or steroid-dependent nephrotic syndrome, consider steroid-sparing agents such as cyclophosphamide, levamisole, or calcineurin inhibitors 2
• For steroid-resistant cases, kidney biopsy is indicated to guide further management 1

Common Pitfalls and Caveats

• Avoid using weight-based dosing (2 mg/kg/day) in small children as it may result in underdosing compared to BSA-based dosing (60 mg/m²/day) 6
• Do not use prophylactic antibiotics routinely unless patients are receiving high-dose immunosuppression 1
• Avoid prolonged steroid therapy without considering steroid-sparing agents in frequently relapsing or steroid-dependent cases 2
• Do not delay kidney biopsy in adults or in children with atypical presentations or steroid resistance 1, 3
• Remember that response to steroids may take longer in adults (up to 16 weeks) compared to children (average 11 days) 7