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

Initial Management of Nephrotic Syndrome

Begin with high-dose oral prednisone at 1 mg/kg/day (maximum 80 mg) for adults or 60 mg/m²/day (maximum 60-80 mg) for children as first-line therapy, combined with sodium restriction, loop diuretics for edema, and ACE inhibitors/ARBs for proteinuria control. 1, 2, 3

Immediate Diagnostic Confirmation and Workup

Before initiating treatment, confirm the diagnosis and exclude secondary causes:

• Confirm nephrotic-range proteinuria using 24-hour urine collection or spot urine protein-to-creatinine ratio 1, 3
• Exclude secondary causes including diabetes mellitus, systemic lupus erythematosus, infections (HIV, hepatitis B/C), hematologic malignancies, and medication-induced causes 1, 4
• Obtain kidney biopsy in adults before starting immunosuppression to identify the underlying pathology (minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy) 1, 3, 5
• Defer biopsy in children with typical presentation (age 1-10 years, no hematuria, normal blood pressure, normal renal function) if they respond to initial steroid therapy 1, 3

Corticosteroid Protocol

For Children:

• Prednisone 60 mg/m²/day (maximum 60-80 mg) as a single daily dose for 4-6 weeks 2, 3, 6
• After achieving remission (urine protein trace/negative for 3 consecutive days), switch to 40 mg/m² on alternate days (maximum 40 mg) for 2-6 months with gradual tapering 2, 6
• Total treatment duration should be at least 12 weeks, with evidence supporting up to 6 months to reduce relapse rates 2

For Adults:

• Prednisone 1 mg/kg/day (maximum 80 mg) as a single daily dose, or 2 mg/kg on alternate days (maximum 120 mg) 1, 2, 3
• Continue high-dose therapy for minimum 4 weeks if remission achieved, or up to 16 weeks if remission not yet achieved 1, 3
• After achieving complete remission, taper slowly over 6 months 1, 3

Critical pitfall: Do not declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy has been completed; partial responses may take up to 16 weeks in adults 2, 7

Supportive Management (Start Immediately)

Edema Control:

• Restrict dietary sodium to <2.0 g/day 1, 2
• Loop diuretics (furosemide) as first-line for managing severe edema and anasarca 1, 2
• Avoid routine IV albumin infusions; use only if clinical indicators of hypovolemia are present (hypotension, tachycardia, poor perfusion), not based on serum albumin levels alone 1, 2
• Avoid IV saline, which worsens edema 2

Proteinuria and Blood Pressure Management:

• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria reduction and blood pressure control 1
• Target systolic blood pressure <120 mmHg in adults using standardized office BP measurement 1

Infection Prevention (Critical Priority)

Patients with nephrotic syndrome are at high risk for serious bacterial infections, particularly encapsulated organisms:

• Administer pneumococcal vaccine (23-valent or conjugate) before or early in immunosuppressive therapy 2, 3
• Give annual influenza vaccination to patients and household contacts 2, 3
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 1
• Avoid live vaccines in children receiving immunosuppressive agents 3

Alternative First-Line Therapy

For patients with contraindications to high-dose corticosteroids (uncontrolled diabetes, severe psychiatric conditions, severe osteoporosis, morbid obesity):

• Calcineurin inhibitors (CNIs) as first-line therapy 1, 2, 3
  • Cyclosporine: 3-5 mg/kg/day divided into 2 doses 8, 1, 2
  • Tacrolimus: 0.1-0.2 mg/kg/day divided into 2 doses for children, or 0.05-0.1 mg/kg/day for adults 2

Monitoring Treatment Response

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio 2, 3
• Complete remission is defined as urine protein <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 2
• Regularly assess kidney function to evaluate treatment response 1, 3
• Monitor for medication side effects, particularly with long-term immunosuppressive therapy 1, 3

Management of Steroid-Resistant Disease

If no response after 8 weeks of adequate corticosteroid therapy:

• Confirm steroid resistance and perform kidney biopsy if not already done 3
• Switch to calcineurin inhibitors (cyclosporine or tacrolimus) as initial therapy for steroid-resistant cases 3
• Continue CNI therapy for minimum 6 months; stop if no remission achieved 3
• If at least partial remission by 6 months, continue CNIs for minimum 12 months 3

Special Considerations for Frequently Relapsing Disease

For children with frequent relapses (≥2 relapses in 6 months) or steroid-dependent disease:

• Consider steroid-sparing agents including cyclophosphamide (2 mg/kg/day for 8-12 weeks), levamisole (2.5 mg/kg on alternate days), or calcineurin inhibitors 8, 2, 6, 7
• Cyclophosphamide maximum duration: 12 weeks with maximum cumulative dose <200 mg/kg to minimize gonadal toxicity 8, 7

Common pitfall: In children, dosing prednisone at 2 mg/kg/day is not equivalent to 60 mg/m²/day for patients weighing <30 kg; the weight-based dosing results in significantly lower doses and may lead to treatment failure 9