What is the typical treatment for nephrotic syndrome?

Treatment of Nephrotic Syndrome

Corticosteroids are the first-line treatment for nephrotic syndrome, with prednisone 60 mg/m²/day (maximum 60 mg) for children or 1 mg/kg/day (maximum 80 mg) for adults, continued for at least 4-6 weeks followed by alternate-day dosing with gradual tapering over 12-16 weeks total. 1, 2, 3

Initial Corticosteroid Therapy

For Children

• Begin with prednisone 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) as a single daily dose 2, 3
• Continue daily dosing for 6 weeks to maximize initial response 4, 2
• Transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg on alternate days) 2, 3
• Continue alternate-day dosing for 6 weeks with gradual tapering 4
• Total treatment duration should be at least 12 weeks, with evidence supporting up to 6 months for reduced relapse rates 1, 2

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) 4, 1, 3
• Continue high-dose therapy for minimum 4 weeks, up to 16 weeks as tolerated or until complete remission 1, 3
• Adults typically require longer treatment duration (>16 weeks) to achieve remission rates of 80% compared to 50-60% with shorter courses 4
• After achieving complete remission, taper corticosteroids slowly over 6 months 3

Critical pitfall: Do not declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy has been completed; continue up to 16 weeks if partial response is occurring 1

Immediate Supportive Management

Edema Control

• Loop diuretics (furosemide) are first-line agents for managing 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; use only if clinical indicators of hypovolemia are present (hypotension, tachycardia, poor perfusion), not based on serum albumin levels alone 1, 3
• Avoid intravenous saline administration, which can worsen edema 1

Proteinuria Management

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

Management of Relapses

Infrequent Relapses

• Treat with prednisone 60 mg/m²/day or 2 mg/kg (maximum 60 mg/day) until remission for at least 3 days 1, 2
• After achieving remission, switch to alternate-day prednisone (40 mg/m² or 1.5 mg/kg) for at least 4 weeks 1, 2

Frequent Relapses 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 1
• Consider steroid-sparing agents including cyclophosphamide, levamisole, calcineurin inhibitors (cyclosporine, tacrolimus), mycophenolate mofetil, or rituximab 4, 1, 2, 3

Important note: More than half of all patients who are initially steroid responsive will experience relapses; those who relapse frequently (≥2 episodes within 6 months) have greater risk of becoming steroid-dependent 4

Alternative First-Line Therapy

For patients with contraindications to high-dose corticosteroids (uncontrolled diabetes mellitus, severe psychiatric conditions, severe osteoporosis, or morbid obesity with elevated HbA1c), consider calcineurin inhibitors as first-line therapy: 1, 3

• Cyclosporine: 3-5 mg/kg/day in divided doses 4, 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
• Cyclosporine produces complete remissions in 85% of children and 79% of adults with steroid dependence, and in 67% of children and 61% of adults with steroid resistance 5

Steroid-Sparing Agents for Relapsing Disease

Cyclophosphamide

• Dose: 2.0-2.5 mg/kg/day for 8-12 weeks 4
• Complete remission reported in 81% of adults, with partial remission in additional 8.5% 4
• Children with frequently relapsing nephrotic syndrome achieve longer remissions with cytotoxic agents than those with steroid dependency 4
• Risk of gonadal toxicity is minimized with total doses below 200 mg/kg 5

Levamisole

• Dose: 2.5 mg/kg given on alternate days 4
• Reduces relapses in children but efficacy limited to treatment period only 4

Mycophenolate Mofetil/Mycophenolic Acid

• Has induced stable remission in children and adults with frequent relapses, though patient numbers in studies were small 4
• A 2018 randomized controlled trial showed that low-dose prednisone (0.5 mg/kg/day) plus enteric-coated mycophenolate sodium was not superior to standard high-dose prednisone regimen 6

Infection Prevention

Critical for all patients on immunosuppressive therapy:

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

Monitoring During Treatment

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio to assess treatment response 1
• Complete remission is defined as: urine protein <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 1, 2
• Relapse is defined as: ≥3+ protein on urine dipstick for 3 consecutive days or uPCR ≥2000 mg/g (≥200 mg/mmol) 2
• Regularly assess kidney function and monitor for medication side effects, particularly with long-term immunosuppressive therapy 3

Special Populations

Children Under 1 Year

• Do not treat with standard regimen without further evaluation, as they are more likely to have genetically definable causes requiring different management 2, 3
• Refer to specialized pediatric nephrology units 3

Elderly Patients

• Particular risk of hip osteonecrosis with prolonged glucocorticoid therapy, especially in post-menopausal women 4
• Increased risk of severe acute tubular necrosis associated with minimal change disease in elderly patients with pre-existing severe hypertension 4

Common Pitfalls to Avoid

• Do not discontinue steroids too rapidly, as this increases relapse risk 2
• Do not stop therapy prematurely if partial response is occurring; continue up to 16 weeks 1
• Approximately 80% of children will experience at least one relapse, and 50% will have frequent relapses or become steroid-dependent 2
• During upper respiratory tract infections in children with frequent relapses, daily prednisone at 0.5 mg/kg/day for 5-7 days may reduce relapse risk 2
• Monitor for steroid side effects including glucose intolerance, cushingoid features, infections, and hip osteonecrosis 4, 7