Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Division for Clinical Trials, Department of Clinical Research, Center for Clinical Research and Development, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Pediatr Nephrol. 2020 Jan;35(1):17-24. doi: 10.1007/s00467-018-4166-1. Epub 2018 Dec 18.
Patients with steroid-resistant nephrotic syndrome (SRNS) who develop resistance to immunosuppressive agents, defined as refractory SRNS, have poor renal outcomes. Although the chimeric anti-CD20 monoclonal antibody rituximab has shown efficacy for frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome, its efficacy for refractory SRNS remains uncertain due to limited data. According to previous case reports, 50.4% of patients with refractory SRNS showed clinical improvements after rituximab treatment. Remission rates in patients with initial steroid resistance and late steroid resistance were 43.9 and 57.7%, respectively, and 41.5 and 63.6% in patients with focal segmental glomerulosclerosis and minor glomerular abnormalities, respectively. However, various factors (race, disease severity, number of rituximab doses, concomitant treatments, and observation period) differed among these observational studies and their consensus may also have been affected by potential publication bias. Rituximab monotherapy may have some degree of efficacy and lead to satisfactory outcomes in a subset of patients with refractory SRNS. However, administration of concomitant treatments during rituximab-mediated B cell depletion, such as methylprednisolone pulse therapy, daily oral prednisolone therapy, and immunosuppressive agents, may lead to better outcomes in these patients. Large-scale, multi-center prospective studies are needed to evaluate the efficacy and safety of such regimens.
患有激素抵抗性肾病综合征 (SRNS) 的患者，如果对免疫抑制剂产生耐药性（即难治性 SRNS），则肾脏预后较差。虽然嵌合抗 CD20 单克隆抗体利妥昔单抗已显示出对频繁复发的肾病综合征和激素依赖性肾病综合征有效，但由于数据有限，其对难治性 SRNS 的疗效仍不确定。根据之前的病例报告，50.4%的难治性 SRNS 患者在利妥昔单抗治疗后临床症状得到改善。对初始激素耐药和晚期激素耐药的患者，缓解率分别为 43.9%和 57.7%，对局灶节段性肾小球硬化和轻微肾小球病变的患者，缓解率分别为 41.5%和 63.6%。然而，这些观察性研究中的各种因素（种族、疾病严重程度、利妥昔单抗剂量、伴随治疗和观察期）存在差异，其共识也可能受到潜在的发表偏倚的影响。利妥昔单抗单药治疗可能在难治性 SRNS 的一部分患者中具有一定疗效，并带来令人满意的结果。然而，在利妥昔单抗介导的 B 细胞耗竭期间给予伴随治疗，如甲基强的松龙冲击治疗、每日口服泼尼松治疗和免疫抑制剂，可能会使这些患者获得更好的结果。需要进行大规模、多中心的前瞻性研究来评估这些方案的疗效和安全性。
