Continuous B-cell depletion in frequently relapsing, steroid-dependent and steroid-resistant nephrotic syndrome
Continuous B-cell depletion in frequently relapsing, steroid-dependent and steroid-resistant nephrotic syndrome
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DOI：
10.1093/ckj/sfy067
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发表时间：
2019-04-01
影响因子：
4.6
通讯作者：
Niles, John L.
中科院分区：
文献类型：
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作者：
Cortazar, Frank B.;Rosenthal, Jillian;Niles, John L.
背景 患有频繁复发（FR）、类固醇依赖性（SD）和类固醇抵抗（SR）肾病综合征的患者是一个治疗挑战，治疗选择有限。在这里，我们回顾性分析了利妥昔单抗诱导的持续 B 细胞耗竭在这些人群中的疗效和安全性。方法纳入年龄至少 18 岁、患有 FR、SD 或 SR 微小病变 (MCD) 或原发性局灶节段性肾小球硬化症 (FSGS) 并接受持续 B 细胞耗竭策略治疗的患者。部分缓解 (PR) 定义为尿蛋白：肌酐比 (UPCR) 为 3.5g/g，且 UPCR 较基线降低 50%。完全缓解 (CR) 定义为 UPCR 0.3g/g。结果 我们确定了 20 名符合纳入标准的 MCD (n=13) 或 FSGS (n=7) 患者。所有患者均患有 SD (n=12)、SR (n=7) 或 FR (n=1) 疾病。患者接受中位 9 剂利妥昔单抗 [四分位距 (IQR) 7.5, 11]，中位治疗时间为 28 个月 (IQR 23, 41)。 12 个月时，泼尼松从开始使用利妥昔单抗时的中位剂量每天 60 mg (IQR 40, 60) 减至每天 4.5 mg (IQR 0, 5.5)。所有患者均达到 PR。 13 名 FR 或 SD 疾病患者中有 11 名发生 CR，但 7 名 SR 疾病患者中只有 1 名发生 CR（对数秩 P=0.01）。发生 4 例复发，全部发生在 SR 疾病患者中。 70.3 患者年发生了 3 次严重感染。 结论 持续 B 细胞耗竭是治疗复杂性肾病综合征的一种治疗选择。需要进行更多研究来阐明该策略的效用。
Background Patients with frequently relapsing (FR), steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome are a therapeutic challenge with limited treatment options. Here, we retrospectively analyze the efficacy and safety of rituximab-induced continuous B-cell depletion in these populations.Methods Patients were included if they were at least 18years of age and had FR, SD or SR minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) and were treated with a strategy of continuous B-cell depletion. Partial remission (PR) was defined as a urinary protein:creatinine ratio (UPCR) of 3.5g/g and a 50% reduction in the UPCR from baseline. Complete remission (CR) was defined as a UPCR 0.3g/g.Results We identified 20 patients with MCD (n=13) or FSGS (n=7) who fulfilled the inclusion criteria. All patients had either SD (n=12), SR (n=7) or FR (n=1) disease. Patients received a median of nine rituximab doses [interquartile range (IQR) 7.5, 11] and were treated for a median time of 28months (IQR 23, 41). Prednisone was weaned from a median of 60mg daily (IQR 40, 60) at rituximab initiation to 4.5mg daily (IQR 0, 5.5) by 12months. All patients achieved PR. CR occurred in 11 of 13 patients with FR or SD disease, but only 1 of 7 patients with SR disease (logrank P=0.01). Four relapses occurred, all in patients with SR disease. Three serious infections occurred over 70.3 patient-years.Conclusion Continuous B-cell depletion is a therapeutic option in the management of complicated nephrotic syndrome. Additional studies are needed to clarify the utility of this strategy.