Proposed Topic (Most preferred): :
Research and Innovations (new projects / technology / innovations / service models)
Authors (including presenting author) :
Eugene Yu-hin Chan, Alison Lap-tak Ma, Aditi Sinha, Ellen LM Yu, Naureen Akhtar, Andrea Angeletti, Arvind Bagga, Sushmita Banerjee, Olivia Boyer, Chang-Yien Chan, Anna Francis, Gian Marco Ghiggeri, Riku Hamada, Pankaj Hari, Nakysa Hooman, Luke Sydney Hopf, Mohamad Ikram I, Iftikhar Ijaz, Dmytro D. Ivanov, Suprita Kalra, Hee Gyung Kang, Laura Lucchetti, Francesca Lugani, William Morello, María Dolores Camargo Muñiz, Subal Kumar Pradhan, Larisa Prikhodina, Reem H. Raafat, Rajiv Sinha, Sharon Teo, Kouki Tomari, Marina Vivarelli, Hazel Webb, Hui Kim Yap, Desmond Yat-hin Yap, Kjell Tullus
Affiliation :
Paediatric Nephrology Centre, Hong Kong Children’s Hospital, Hong Kong SAR
Introduction :
Children with steroid-resistant nephrotic syndrome (SRNS) are at high risk of developing kidney failure.
Objectives :
To evaluate the efficacy and safety of rituximab as rescue therapy in SRNS through an international, multi-centre study.
Methodology :
We initiated and conducted a retrospective cohort study at 28 paediatric nephrology centres from 19 countries in Asia, Europe, North America and Oceania. Children with SRNS treated with rituximab were analysed according to the duration of calcineurin inhibitors (CNIs) treatment before rituximab [≥6 months (CNI-resistant) and <6 months]. Primary outcome was complete/partial remission (CR/PR) as defined by international definitions. Secondary outcomes included kidney survival and adverse events.
Result & Outcome :
Two-hundred-forty-six children (age, 6.94.2 years; 136 boys; 57% focal segmental glomerulosclerosis, FSGS) were followed for 32.4 (IQR, 18.6-64.9) months after rituximab. All patients were in non-remission before rituximab. 146 and 100 children received CNIs for ≥ and <6 months before rituximab, respectively. Patients with CNI-resistant SRNS, compared to those treated with CNIs for <6 months, had lower rates of NS remission (CR/PR) at 6- (36% vs 52%) and 12-months (35% vs 55%) post-rituximab (ps<0.01). Among CNI-resistant patients, multivariable analysis demonstrated that subnephrotic-range proteinuria at rituximab (ORadj 5.6, 95%CI 1.1-37.1, p=0.049) and late SR (ORadj 2.6, 95%CI 1.1-6.2, p=0.03) were predictive of CR/PR at 12-months. Non-response to rituximab (HRadj 7.0, 95%CI 2.2-21.8, p<0.001), pre-existing CKD (HRadj 2.4, 95%CI 1.0-5.6, p=0.04), and FSGS (HRadj 4.3, 95%CI 1.4-13.2, p=0.01) were predictors for kidney failure and/or death. Adverse events occurred in 30.5% and most were mild. In conclusion, rituximab enhances remission in a subset of children with SRNS. Late SR and subnephrotic-range proteinuria predict favourable response to rituximab in children with CNI-resistant SRNS.
