利妥昔单抗治疗儿童激素耐药性肾病综合征的疗效及预后不良的危险因素：一项多中心研究。

Efficacy of rituximab and risk factors for poor prognosis in patients with childhood-onset steroid-resistant nephrotic syndrome: a multicenter study.

机构信息

Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.

Division of Nephrology, Saitama Children's Medical Center, Saitama, Japan.

出版信息

Pediatr Nephrol. 2024 Oct;39(10):2979-2988. doi: 10.1007/s00467-024-06422-5. Epub 2024 Jun 4.

DOI:10.1007/s00467-024-06422-5

PMID:38834892

Abstract

BACKGROUND

The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown.

METHODS

This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated.

RESULTS

The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5.

CONCLUSION

Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS.

摘要

背景

利妥昔单抗治疗激素耐药性肾病综合征（SRNS）的疗效存在争议。我们之前曾报道过，利妥昔单抗联合甲基强的松龙冲击疗法（MPT）和免疫抑制剂治疗与良好的疗效相关。但是，利妥昔单抗治疗后反应不佳的风险因素仍不清楚。

方法

本回顾性研究纳入了在四家儿科肾脏科接受利妥昔单抗治疗的 45 例儿童起病的 SRNS 患者。在利妥昔单抗治疗 1 年后，根据治疗效果将患者分为完全缓解（CR）、部分缓解（PR）和无缓解（NR）。主要结局为 CR、PR 和 NR 的发生率。使用多变量逻辑回归计算非 CR 的风险因素。还评估了不良事件以及 1 年后疾病状态与长期预后之间的关系。

结果

1 年后 CR、PR 和 NR 的发生率分别为 69%、24%和 7%。利妥昔单抗治疗后达到 CR 的中位时间为 90 天。利妥昔单抗治疗后中位随访时间为 7.4 年。多变量分析显示，局灶节段肾小球硬化的病理表现和 SRNS 诊断与利妥昔单抗治疗之间的时间间隔较长是反应不佳的显著风险因素。在 SRNS 诊断后 6 个月内和 6 个月后接受利妥昔单抗治疗的患者中，CR 的发生率分别为 90.3%和 21.4%（p<0.001）。5 例患者发展为慢性肾脏病 G5 期，其中 2 例 PR 患者和所有 3 例 NR 患者均发展为慢性肾脏病 G5 期，而 31 例 CR 患者无一例发展为慢性肾脏病 G5 期。