Anti-CD20 agent has been proposed as a rescue therapy for refractory nephrotic syndrome(NS) on the basis of favorable clinical observations. Yet the long-term effect on maintaining remission or the likelihood of becoming rituximab-dependent is unclear and the information on the safety profile of rituximab is limited. This trial was designed to investigate the safety and efficacy of Rituximab in children with refractory NS.

Inclusion Criteria:

(A)steroid/calcineurin inhibitor resistant nephrotic syndrome

1. steroid resistance: no remission after 4 weeks of daily oral corticosteroid (60mg/m2/day)
2. calcineurin inhibitor resistance: no remission after 3 months of therapeutic dose administration of cyclosporine and/or tacrolimus
3. no remission defined by persistent proteinuria of nephrotic range for the last 3 months
4. post-transplant patients were included in the study

(B)steroid-dependent nephrotic syndrome

1. Steroid-dependent patients who had been on various known medications (such as corticosteroids, cyclophosphamide, chlorambucil, calcineurin inhibitors, levamisole ..) continuously for more than 2 years

2. definition of dependency: more than two consecutive relapse events in 2 weeks after discontinuation of steroid or calcineurin inhibitor

   • no improvement in relapsing frequency with calcineurin inhibitor use
   • unable to continue with calcineurin inhibitor due to side effects
   • unable to continue with calcineurin inhibitor due to prolonged use (over 2 years)
   • other conditions in which the clinician considers difficult to control disease with steroids or calcineurin inhibitors only.

Exclusion Criteria:

• previous rituximab use
• secondary nephrotic syndrome
• estimated GFR <60mL/min/1.73m2 or under 50% of age-matched standard GFR
• chronic or acute active infection (e.g. hepatitis B,C, herpes, varicella zoster)
• prior live vaccine inoculation within 1 month (from the study enrollment)
• cardiovascular diseases, pulmonary or pleural diseases
• uncontrolled hypertension
• leukocytopenia (absolute neutrophil count <1500/mm3) or thrombocytopenia (<75000/mm3)
• pregnancy