What is the initial treatment for nephrotic syndrome in adolescents?

Initial Treatment for Nephrotic Syndrome in Adolescents

Begin oral prednisone at 60 mg/m²/day (or 2 mg/kg/day) with a maximum of 60 mg daily as a single morning dose for 6 weeks, followed by 40 mg/m² on alternate days for another 6 weeks, then taper over 4 weeks for a total treatment duration of 16 weeks. 1, 2

Treatment Protocol

Daily Phase (Weeks 1-6)

• Administer prednisone 60 mg/m²/day or 2 mg/kg/day as a single daily dose (maximum 60 mg/day) 1, 2
• Continue this daily dosing for the full 6 weeks regardless of when remission occurs 1
• Remission is defined as urine protein <1+ on dipstick for 3 consecutive days or urine protein-to-creatinine ratio <200 mg/g 2

Alternate-Day Phase (Weeks 7-12)

• Switch to prednisone 40 mg/m² or 1.5 mg/kg as a single morning dose on alternate days 1, 2
• Maximum dose is 40 mg on alternate days 1
• Continue for 6 weeks 1

Tapering Phase (Weeks 13-16)

• Taper prednisone by 10 mg/m² per week until reaching 5 mg on alternate days 1
• Round doses up to account for 5-mg tablets 1
• Total treatment duration is 16 weeks 1

Critical Considerations for Adolescents

Age-Specific Factors

• Adolescents diagnosed with nephrotic syndrome after age 12 years require kidney biopsy before initiating treatment, as they are more likely to have secondary causes or non-minimal change disease 1
• This differs from younger children (ages 1-12 years) who can be treated empirically without biopsy 1, 3

Defining Treatment Response

• If no remission is achieved by 6 weeks of daily prednisone, the diagnosis of steroid-resistant nephrotic syndrome (SRNS) is confirmed 1
• A minimum of 8 weeks of corticosteroid treatment is needed to definitively define steroid resistance 1
• Approximately 85% of children and adolescents with idiopathic nephrotic syndrome achieve complete remission with corticosteroids 3

Management of Relapses

Infrequent Relapses

• Treat with prednisone 60 mg/m²/day (maximum 60 mg/day) until remission for at least 3 consecutive days 1, 2
• Switch to alternate-day prednisone 40 mg/m² for 4 weeks 2, 4
• Taper by 10 mg/m² per week to complete treatment 1

Frequent Relapses or Steroid-Dependent Disease

• Consider steroid-sparing agents rather than continuing corticosteroids alone 2, 4
• First-line steroid-sparing agent is levamisole (if available), followed by cyclophosphamide 1
• Rituximab is also recommended for steroid-dependent or frequently relapsing disease 2, 4
• Approximately 70% of children experience at least one relapse, and 50% develop frequent relapses or steroid dependence 2

Steroid-Resistant Nephrotic Syndrome

Second-Line Treatment

• Use calcineurin inhibitors (cyclosporine or tacrolimus) as initial second-line therapy for steroid-resistant disease 4, 3
• Approximately 70% of patients with non-genetic SRNS achieve complete or partial remission with calcineurin inhibitors 3
• Require kidney biopsy in all children with SRNS except those with known infection/malignancy-associated disease or confirmed genetic causes 1

Genetic Testing

• One-third of patients with SRNS have mutations in key podocyte genes 3
• Genetic testing should be obtained as soon as possible, ideally within 2 weeks of confirming steroid resistance 1
• Children with genetic forms typically do not respond to immunosuppression 3

Common Pitfalls and Caveats

Duration of Treatment

• Do not use the shorter 8-week regimen (4 weeks daily + 4 weeks alternate-day) as this significantly increases relapse risk 1, 5
• Longer initial treatment courses (up to 6-7 months) further reduce relapse rates without increasing adverse effects 2, 5
• There is an inverse linear relationship between treatment duration and relapse risk 5

Monitoring and Adverse Effects

• Monitor for steroid side effects including obesity, growth suppression, hypertension, diabetes, osteoporosis, and adrenal suppression 6, 7
• Growth velocity may be the most sensitive indicator of systemic corticosteroid exposure in pediatric patients 6
• Titrate to the lowest effective dose to minimize growth effects 6

Infection Risk

• During upper respiratory tract infections in children with frequent relapses, consider daily prednisone 0.5 mg/kg/day for 5-7 days to reduce relapse risk 2
• Infection remains the most important cause of death in nephrotic syndrome despite corticosteroid therapy reducing mortality to approximately 3% 5
• Patients on corticosteroids may exhibit diminished response to vaccines and should defer routine vaccination until therapy is discontinued if possible 6

Adjunctive Therapy

• Add drugs that inhibit the renin-angiotensin axis for hypertension and reducing residual proteinuria 3
• Manage complications including dyslipidemia, infection risk, and thrombosis 7