What is the initial treatment approach for patients with nephrotic syndrome?

Initial Treatment Approach for Nephrotic Syndrome

Begin corticosteroid therapy immediately with prednisone 60 mg/m²/day (maximum 60 mg) as a single daily dose for 4-6 weeks, followed by alternate-day dosing at 40 mg/m² for 2-6 months with gradual tapering, while simultaneously managing edema with loop diuretics and sodium restriction. 1, 2

Immediate Supportive Management

Edema and Fluid Management:

• Administer loop diuretics (furosemide) as first-line therapy for severe edema and anasarca 1
• Restrict dietary sodium to <2.0 g/day to reduce fluid retention 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 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 2
• Target systolic blood pressure <120 mmHg in adults using standardized office measurement 2

Corticosteroid Protocol

For Children (Pediatric Nephrotic Syndrome):

• Initial episode: Prednisone 60 mg/m²/day (maximum 60 mg) as a single daily dose for 6 weeks 3, 1
• Continuation phase: Switch to 40 mg/m² as a single morning dose on alternate days for another 6 weeks 3
• Tapering: Reduce by 10 mg/m² per week to 5 mg on alternate days 3
• Total duration: 16 weeks for initial episode 3, 1

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, 4
• Continue high-dose therapy for minimum 4 weeks if complete remission achieved, up to 16 weeks if remission not achieved 1, 4
• After achieving remission, taper slowly over 6 months 2, 4

Important Dosing Consideration:

• Note that 2 mg/kg/day is NOT equivalent to 60 mg/m²/day in children weighing <30 kg—the weight-based dosing delivers approximately 15% less medication 5
• Use body surface area (BSA) calculation for more accurate dosing in children 5

Management of Relapses

Infrequent Relapses:

• Prednisone 60 mg/m² or 2 mg/kg (maximum 60 mg/day) daily until remission for at least 3 consecutive days 1, 4
• Follow with alternate-day prednisone (40 mg/m²) for at least 4 weeks 1

Frequently Relapsing or Steroid-Dependent Disease:

• Treat relapses with daily prednisone until remission for at least 3 days 1
• Follow with alternate-day prednisone for at least 3 months 1
• Consider steroid-sparing agents: cyclophosphamide, levamisole, calcineurin inhibitors (cyclosporine or tacrolimus), or mycophenolate mofetil 3, 1, 4

Alternative First-Line Therapy (When Corticosteroids Contraindicated)

Consider calcineurin inhibitors as first-line therapy for patients with:

• Uncontrolled diabetes mellitus 1
• Severe psychiatric conditions 1
• Severe osteoporosis 1
• Morbid obesity with elevated HbA1c 1

Dosing:

• Cyclosporine: 3-5 mg/kg/day in divided doses 1, 4
• Tacrolimus: 0.05-0.1 mg/kg/day in divided doses (adults) or 0.1-0.2 mg/kg/day (children) 1
• Continue CNI therapy for minimum 6 months; if at least partial remission achieved, continue for minimum 12 months 4

Critical Infection Prevention

Vaccination (Before or Early in Immunosuppressive Therapy):

• Administer pneumococcal vaccination (23-valent or conjugate vaccine) 1, 4
• Give annual influenza vaccination to patients and household contacts 1, 4
• Live vaccines are contraindicated in children receiving immunosuppressive agents 4, 6
• Consider prophylactic trimethoprim-sulfamethoxazole for patients on high-dose immunosuppression 2

Monitoring Treatment Response

Daily Monitoring:

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

Regular Assessment:

• Assess proteinuria and kidney function regularly to evaluate treatment response 2, 4
• Monitor for medication side effects, particularly with long-term immunosuppressive therapy 2, 4
• In children, monitor blood pressure, weight, height, intraocular pressure, and evaluate for infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis 6

Diagnostic Workup (Parallel to Treatment Initiation)

Essential Investigations:

• Confirm nephrotic-range proteinuria with 24-hour urine collection or spot urine protein-to-creatinine ratio 2, 4
• Exclude secondary causes: diabetes mellitus, systemic lupus erythematosus, infections, medications review 2, 4

Kidney Biopsy Indications:

• Adults: Generally indicated before initiating immunosuppressive therapy 4
• Children: May defer biopsy if typical presentation and response to initial steroid therapy 2, 4
• Mandatory in children: Steroid-resistant nephrotic syndrome after 8 weeks of adequate therapy 2, 4

Critical Pitfalls to Avoid

Do not declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy completed 1, 4

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

Do not use intravenous albumin routinely—reserve for clinical hypovolemia, not low albumin levels 1

Do not prescribe prednisone by weight alone in children <30 kg—use body surface area calculation 5

Monitor growth velocity in children—this is a more sensitive indicator of systemic corticosteroid exposure than HPA axis testing 6