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

Initial Management of Nephrotic Syndrome

The initial management of nephrotic syndrome requires immediate supportive care with sodium restriction (<2.0 g/day), loop diuretics for edema, and ACE inhibitors/ARBs for proteinuria control, followed by corticosteroid therapy tailored to age and clinical presentation. 1, 2

Immediate Diagnostic Confirmation and Workup

• Confirm nephrotic-range proteinuria using 24-hour urine collection or spot urine protein-to-creatinine ratio before initiating treatment 1, 3
• Exclude secondary causes in all patients by investigating for diabetes mellitus, systemic lupus erythematosus, infections (hepatitis B/C, HIV), hematologic malignancies, and medication-induced causes 1, 4
• Assess for complications including hypovolemia (hypotension, tachycardia, poor perfusion), thromboembolism risk, and infection susceptibility 2

Supportive Management (Initiate Immediately)

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 if 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

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

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, 5
• Continue high-dose therapy for minimum 4 weeks if complete remission is achieved, and up to 16 weeks if remission is not achieved 1, 2, 3
• Do not declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy has been completed 2, 3
• After achieving remission, taper steroids slowly over a period of up to 6 months 1, 3

Children

• Administer prednisone 60 mg/m²/day (maximum 60-80 mg/day) as a single daily dose for 4-6 weeks 1, 2, 3
• Follow with alternate-day dosing at 40 mg/m² per dose (maximum 40 mg on alternate days) for 2-5 months with gradual tapering 2
• Total initial treatment duration should be at least 12 weeks, with evidence supporting up to 6 months for reduced relapse rates 2

Critical caveat: The dosage of 2 mg/kg/day versus 60 mg/m²/day is not equivalent for patients with weights <30 kg, with 2 mg/kg/day providing significantly lower doses 6. Use body surface area dosing (60 mg/m²/day) for children to ensure adequate treatment.

Kidney Biopsy Decision Algorithm

Children

• Defer biopsy if typical presentation (age 1-10 years, no hematuria, normal complement, normal renal function) and response to initial steroid therapy occurs 1, 3
• Perform biopsy if steroid-resistant after 8 weeks of adequate therapy 1, 3
• Consider genetic testing as first-line in congenital or early-onset cases (age <1 year) 1

Adults

• Kidney biopsy is generally indicated before initiating immunosuppressive therapy 3, 7
• Exception: Defer biopsy if serum anti-phospholipase A2 receptor antibodies are positive, which is diagnostic of membranous nephropathy 4

Alternative First-Line Therapy

Consider calcineurin inhibitors (CNIs) as first-line therapy for patients with relative contraindications or intolerance to high-dose corticosteroids, including uncontrolled diabetes mellitus, severe psychiatric conditions, severe osteoporosis, or morbid obesity 1, 2, 3

• Cyclosporine: 3-5 mg/kg/day divided into 2 doses 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

Infection Prevention (Critical Priority)

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

Monitoring During Initial Treatment

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio to assess treatment response 2, 3
• Define complete remission 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 and detect complications 1, 3
• Monitor for medication side effects, particularly with long-term immunosuppressive therapy 1, 3

Common Pitfalls to Avoid

• Do not stop therapy prematurely if partial response is occurring; continue up to 16 weeks in adults 2
• Do not use intravenous fluids routinely; concentrate oral fluid intake if necessary 1
• Do not base albumin infusion decisions on serum albumin levels alone; use only for clinical hypovolemia 2
• Do not underdose prednisone in children by using weight-based dosing (2 mg/kg/day) instead of body surface area dosing (60 mg/m²/day) for those <30 kg 6