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

Initial Treatment Approach for Nephrotic and Nephritic Syndrome

For patients with nephrotic and nephritic syndrome, the initial treatment should include corticosteroids, with prednisone or prednisolone given at a daily single dose of 1 mg/kg (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg) for adults, while children should receive 60 mg/m² per day (maximum 60 mg) for 4-6 weeks followed by alternate-day therapy. 1, 2, 3

Diagnostic Approach

• Confirm nephrotic-range proteinuria with 24-hour urine collection or spot urine protein-to-creatinine ratio 2
• Perform investigations to exclude secondary causes (diabetes, lupus, infections, medications) 2
• In adults, kidney biopsy is generally indicated before initiating immunosuppressive therapy 2
• In children with typical presentation, biopsy may be deferred if there is response to initial steroid therapy 2, 3
• Biopsy is indicated in steroid-resistant nephrotic syndrome in children 1

Initial Corticosteroid Protocol

For Adults:

• Administer prednisone/prednisolone at 1 mg/kg/day (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg) 1, 2
• Continue high-dose corticosteroids for a minimum of 4 weeks if complete remission is achieved, and up to 16 weeks if remission is not achieved 1
• After achieving remission, taper steroids slowly over a period of up to 6 months 1

For Children:

• Begin with oral prednisone 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) as a single daily dose 3
• Note: Using weight-based dosing (2 mg/kg/day) typically results in lower doses than BSA-based dosing (60 mg/m²/day), especially for children weighing <30 kg 4
• Continue daily dosing for 4-6 weeks 3
• After daily phase, transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg) 3
• Continue alternate-day dosing for 2-5 months with gradual tapering 3
• Total treatment duration should be at least 12 weeks to reduce relapse risk 3

Supportive Management

• Restrict dietary sodium to <2.0 g/day to reduce edema 2
• Use loop diuretics as first-line agents for edema management 2
• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria and blood pressure control 2
• Target systolic blood pressure <120 mmHg in adults using standardized office BP measurement 2
• Avoid intravenous fluids and saline; concentrate oral fluid intake if necessary 2
• Use albumin infusions based on clinical indicators of hypovolemia, not serum albumin levels 2

Management of Steroid-Resistant Nephrotic Syndrome

• Steroid resistance is defined after a minimum of 8 weeks of treatment with corticosteroids 1
• For steroid-resistant cases, calcineurin inhibitors (CNIs) are recommended as initial therapy 1
• CNI therapy should be continued for a minimum of 6 months and then stopped if remission is not achieved 1
• If at least partial remission is achieved by 6 months, continue CNIs for a minimum of 12 months 1
• Combine low-dose corticosteroid therapy with CNI therapy 1
• Add ACE inhibitors or ARBs for children with steroid-resistant nephrotic syndrome 1

Management of Frequently Relapsing Nephrotic Syndrome

• Treat relapses with daily prednisone at 60 mg/m² or 2 mg/kg (maximum 60 mg/day) until remission for at least 3 consecutive days 5
• After achieving remission, switch to alternate-day prednisone for at least 3 months 5
• Consider corticosteroid-sparing agents for children with frequent relapses or steroid dependence 5:
  • Levamisole (2.5 mg/kg on alternate days for at least 12 months) 5
  • Cyclophosphamide (2 mg/kg/day for 8-12 weeks, maximum cumulative dose 168 mg/kg) 5
  • Calcineurin inhibitors (cyclosporine or tacrolimus) 5
  • Mycophenolate mofetil (1200 mg/m²/day in two divided doses for at least 12 months) 5
  • Rituximab for steroid-dependent cases with continuing frequent relapses despite optimal therapy 5

Infection Prevention

• Administer pneumococcal vaccination 2
• Give annual influenza vaccination to patients and household contacts 2
• Defer vaccination with live vaccines until prednisone dose is below 1 mg/kg daily or 2 mg/kg on alternate days 1
• Live vaccines are contraindicated in children receiving immunosuppressive agents 1
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 2

Monitoring and Follow-up

• Regularly assess proteinuria and kidney function to evaluate treatment response 2
• Monitor for side effects of medications, particularly with long-term immunosuppressive therapy 2
• Regular assessment of kidney function is especially important in patients receiving calcineurin inhibitors 5

Common Pitfalls and Caveats

• Children younger than 1 year often have genetic forms of nephrotic syndrome and should be managed differently 3
• Avoid discontinuing steroids too rapidly as this increases relapse risk 3
• Second courses of alkylating agents should be avoided due to cumulative toxicity 5
• Approximately 80% of children will experience at least one relapse, and 50% will have frequent relapses or become steroid-dependent 3