Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR; Paediatric Nephrology Centre, Department of Paediatric and Adolescent Medicine, Hong Kong Children's Hospital, Kowloon Bay, Hong Kong SAR.
Division of Nephrology, Department of Pediatrics, Indian Council of Medical Research Advanced Center for Research in Nephrology, India Institute of Medical Sciences, New Delhi, India.
Kidney Int. 2024 Dec;106(6):1146-1157. doi: 10.1016/j.kint.2024.09.011. Epub 2024 Oct 10.
The efficacy and safety of rituximab in childhood steroid-resistant nephrotic syndrome (SRNS) remains unclear. Therefore, we conducted a retrospective cohort study at 28 pediatric nephrology centers from 19 countries in Asia, Europe, North America and Oceania to evaluate this. Children with SRNS treated with rituximab were analyzed according to the duration of calcineurin inhibitors (CNIs) treatment before rituximab [6 months or more (CNI-resistant) and under 6 months]. Primary outcome was complete/partial remission (CR/PR) as defined by IPNA/KDIGO guidelines. Secondary outcomes included kidney failure and adverse events. Two-hundred-forty-six children (mean age, 6.9 years; 136 boys; 57% focal segmental glomerulosclerosis, FSGS) were followed a median of 32.4 months after rituximab. All patients were in non-remission before rituximab. (146 and 100 children received CNIs for 6 month or more or under 6 months before rituximab, respectively). In patients with CNI-resistant SRNS, the remission rates (CR/PR) at 3-, 6-, 12- and 24-months were 26% (95% confidence interval 19.3-34.1), 35.6% (28.0-44.0), 35.1% (27.2-43.8) and 39.1% (29.2-49.9), respectively. Twenty-five patients were in PR at 12-months, of which 22 had over 50% reduction in proteinuria from baseline. The remission rates among children treated with CNIs under 6 months before rituximab were 42% (32.3-52.3), 52% (41.8-62.0), 54% (44.3-64.5) and 60% (47.6-71.3) at 3-, 6-, 12-, and 24-months. Upon Kaplan-Meier analysis, non-remission and PR at 12-months after rituximab, compared to CR, were associated with significantly worse kidney survival. Adverse events occurred in 30.5% and most were mild. Thus, rituximab enhances remission in a subset of children with SRNS, is generally safe and CR following rituximab is associated with favorable kidney outcome.
利妥昔单抗治疗儿童激素耐药性肾病综合征（SRNS）的疗效和安全性尚不清楚。因此，我们在亚洲、欧洲、北美和大洋洲的 28 个儿科肾脏病中心进行了一项回顾性队列研究，以对此进行评估。根据利妥昔单抗治疗前环孢素抑制剂（CNI）的持续时间[6 个月或更长时间（CNI 耐药）和 6 个月以下]，对接受利妥昔单抗治疗的 SRNS 患儿进行分析。主要结局是根据 IPNA/KDIGO 指南定义的完全/部分缓解（CR/PR）。次要结局包括肾功能衰竭和不良事件。246 名儿童（平均年龄 6.9 岁；136 名男孩；57%为局灶节段性肾小球硬化症，FSGS）在接受利妥昔单抗治疗后中位随访 32.4 个月。所有患者在接受利妥昔单抗治疗前均未缓解（分别有 146 名和 100 名儿童接受 CNI 治疗 6 个月或更长时间或 6 个月以下）。在 CNI 耐药性 SRNS 患者中，3、6、12 和 24 个月时的缓解率（CR/PR）分别为 26%（95%置信区间 19.3-34.1）、35.6%（28.0-44.0）、35.1%（27.2-43.8）和 39.1%（29.2-49.9）。25 名患者在 12 个月时达到 PR，其中 22 名患者蛋白尿较基线降低 50%以上。在接受利妥昔单抗治疗前 CNI 治疗 6 个月以下的儿童中，3、6、12 和 24 个月时的缓解率分别为 42%（32.3-52.3）、52%（41.8-62.0）、54%（44.3-64.5）和 60%（47.6-71.3）。通过 Kaplan-Meier 分析，与 CR 相比，利妥昔单抗治疗后 12 个月时未缓解和 PR 与肾脏存活率显著降低相关。30.5%的患者发生不良事件，且大多数为轻度不良事件。因此，利妥昔单抗可增强部分 SRNS 患儿的缓解，总体安全性良好，且利妥昔单抗治疗后的 CR 与有利的肾脏结局相关。
