POS-455 RITUXIMAB IN MANAGEMENT OF PEDIATRIC NEPHROTIC SYNDROME

Abstract

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Many studies in the past decade have reported the effectiveness of rituximab for complicated FRNS/SDNS and refractory SRNS. Prospective study 1) To evaluate the efficacy of rituximab in glomerular diseases. 2) To evaluate response of rituximab by complete or partial remission of nephrotic syndrome after two to four doses of rituximab 375mg/m2, during the follow up period of 12 months and the outcome had been assessed using blood and urine biochemistry values (UPCR/24hr urine protein,serum albumin) i.e., Complete remission (UPCR < 0.2), Partial remission (> 50% decrease in proteinuria from base line), CD 19 cells (< 5%) 3)To look for safety of rituximab. The patients included in the study will be given the dosage of rituximab as per body surface area (BSA) i.e., 375 mg/m2 two to four doses and followed up for a period of 12 months.REGIMEN: 375 mg/m2 Rituximab (2 doses for SDNS, 4 doses for SRNS) after premedication. Inclusion criteria: Patients of age groups <18 yrs were included in the study. Patients with nephrotic syndrome who had received a trial of steroids, alkylating agent and at least 6 months therapy of calcineurin inhibitor had received the novel drug Rituximab. Exclusion criteria: Patients with active focus of infection (Acute/Chronic). Serological evidence of current or past HIV/Hepatitis B/Hepatitis C infection. Known allergic reaction to rituximab. Patients/Parents not willing to give informed consent. Out of 33 patients who received rituximab 18 patients were in SRNS group and 11 were SDNS. The mean age of the patients who used rituximab in SDNS was 13.7+- 9.1 and in SRNS was 10.7+-2.9. In SDNS, FSGS contributed 61% (n=11); MCD33% (n=3) while in SDNS, MCD 72% (n=8); FSGS 27% (n=3). The mean duration of the CNI therapy for SRNS was 20.7=-17.1 months while for SDNS was 18.7+-10.2 months. In SRNS group; Complete remission (CR) was seen in 50.0% while in FSGS 18.1%; partial remission (PR) attained in 33.3% in MCD and in FSGS 27.2% and no remission for 16.6% in MCD and 54.4% in FSGS. In SDNS group, CR was seen in 75.0% in MCD and 33.3% in FSGS; PR obtained in 12.5% in MCD and 66.6% in FSGS; no remission in 12.5% in MCD.The CD19 counts at baseline were 12.6 ± 3.4% of the leukocyte count. After rituximab therapy, CD19 levels were 0.2 ± 0.1 and 0.3 ± 0.2% after two and four doses in patients with SDNS and SRNS, respectively. This study confirm the efficacy of rituximab in patients with difficult nephrotic syndrome; remission was achieved in 50.0% patients with SRNS and a 72.72% patients achieved remission in patients with SDNS. There was a trend toward better response rates in patients with steroid-resistant MCD (83.3%) compared with FSGS (45.45%).