What is the recommended treatment for a 7-year-old child with frequently relapsing nephrotic syndrome?

Treatment of Frequently Relapsing Nephrotic Syndrome in a 7-Year-Old Child

For a 7-year-old child with frequently relapsing nephrotic syndrome, the recommended treatment includes daily prednisone until remission for at least 3 days, followed by alternate-day prednisone for at least 3 months, with consideration of corticosteroid-sparing agents to reduce steroid-related adverse effects. 1, 2

Initial Management of Relapses

• Treat relapses with daily prednisone at 60 mg/m² or 2 mg/kg (maximum 60 mg/day) until the child achieves complete remission for at least 3 consecutive days 1, 2
• After achieving remission, transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg on alternate days) for at least 3 months 1
• Use the lowest dose of alternate-day prednisone necessary to maintain remission without major adverse effects 1
• If alternate-day prednisone is not effective in maintaining remission, consider daily prednisone at the lowest effective dose 1

Corticosteroid-Sparing Therapy Options

When frequent relapses continue or steroid toxicity develops, corticosteroid-sparing agents should be considered. These can be used in the following order (unbiased, based on clinical judgment):

• Calcineurin inhibitors (cyclosporine or tacrolimus) 1, 2
• Cyclophosphamide (2 mg/kg/day for 8-12 weeks, maximum cumulative dose 168 mg/kg) 2
• Levamisole (2.5 mg/kg on alternate days for at least 12 months) 2
• Mycophenolate mofetil (1200 mg/m²/day in two divided doses for at least 12 months) 2, 3
• Rituximab - for children with continuing frequent relapses despite optimal combinations of prednisone and other agents 1, 2

Management During Infections

• The 2025 KDIGO guidelines recommend against routinely giving daily glucocorticoids during episodes of upper respiratory tract infections to reduce relapse risk 1
• However, in selected cases with a history of infection-triggered relapses, consider giving three extra doses of low-dose (0.5 mg/kg per day) daily prednisone at the onset of an upper respiratory tract infection 1, 4

Duration of Therapy

• Corticosteroid-sparing agents should typically be continued for at least 12 months 2
• For calcineurin inhibitors, continue for a minimum of 6 months and stop if partial or complete remission is not achieved; continue for at least 12 months when at least partial remission is achieved by 6 months 1
• Mycophenolate mofetil has shown effectiveness in maintaining remission when used for at least 6 months, with some patients remaining in remission for 18-30 months after stopping therapy 3

Monitoring and Follow-up

• Regularly assess kidney function, especially in patients receiving calcineurin inhibitors 2
• Monitor for adverse effects of corticosteroids (obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, adrenal suppression) 5
• Quantify proteinuria to assess response to therapy 2

Common Pitfalls and Caveats

• Avoid prolonged daily corticosteroid use due to significant adverse effects; transition to alternate-day therapy as soon as remission is achieved 2, 5
• Do not start cyclophosphamide until the child has achieved remission with corticosteroids 2
• Avoid second courses of alkylating agents due to cumulative toxicity 2
• Children younger than 1 year are more likely to have a different (genetically definable) cause for their nephrotic syndrome and should be managed differently 1
• Single-dose daily administration of prednisone is as effective as divided doses and may improve compliance 6

By following this treatment algorithm, the goal is to maintain remission while minimizing steroid exposure and associated adverse effects in children with frequently relapsing nephrotic syndrome.