Rituximab for the second- and third-line therapy of idiopathic membranous nephropathy: a prospective single center study using a new treatment strategy
Rituximab for the second- and third-line therapy of idiopathic membranous nephropathy: a prospective single center study using a new treatment strategy
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DOI：
10.5414/cn107912
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发表时间：
2013-08-01
影响因子：
1.1
通讯作者：
Wolf, Gunter
中科院分区：
文献类型：
--
作者：
Busch, Martin;Ruester, Christiane;Wolf, Gunter
背景：特发性膜性肾病（Idiopathic membranous nephropathy，MN）是肾病综合征的主要病因.常规治疗策略诱导缓解，但复发率高。不同剂量的利妥昔单抗（RTX）在减少MN的蛋白尿方面似乎有效，但长期随访数据很少。研究方法：自2006年以来，共有14例活检证实的MN患者（中位年龄51（26 - 69）岁，4例女性，10例男性）（1 - 4次复发，MN自4（1 - 13）年起）接受RTX治疗（第0、30、60、90天4次剂量RTX 375 mg/m2）。所有患者既往均接受过环孢菌素A免疫抑制治疗，7例接受过烷化剂治疗。在11例患者中，在RTX前2（1 - 10）个月进行了额外的肾活检。结果如下：最后一次RTX输注后3个月，蛋白尿从基线5.5（2.9 - 11.9）g/24 h降至1.8（0.03 - 8.7）g/24 h（p = 0.012）。肌酐清除率保持稳定（3个月时为53（29 - 160）ml/min，基线时为44（29 - 159）ml/min）。到目前为止，患者的中位随访时间为3（1 - 6）年。1年后完全缓解3例（21.4%），部分缓解7例（50.0%）。两次复发发生在1年和3.5年后。RTX前存在肾小球硬化与预后较差相关。结论：每周4次输注RTX是MN二线和三线治疗的合理选择，与其他MN免疫抑制治疗相比，具有更好的安全性。
Background: Idiopathic membranous nephropathy (MN) is a major cause of nephrotic syndrome. Conventional treatment strategies induce remission but the relapse rates are high. Different doses of rituximab (RTX) appeared effective in reducing proteinuria in MN but long-term follow-up data are rare. Methods: Since 2006, a total of 14 patients (median age 51 (26 - 69) years, 4 women, 10 men) with biopsy-proven MN (1 - 4 relapses, MN since 4 (1 - 13) years) were treated with RTX (4 doses of RTX 375 mg/m(2) on Days 0, 30, 60, 90). All patients had prior immunosuppressive therapy with Cyclosporin A, 7 with alkylating agents. In 11 patients, an additional renal biopsy was performed 2 (1 - 10) months before RTX. Results: Three months after the last RTX infusion, proteinuria decreased from a baseline of 5.5 (2.9 - 11.9) g/24 h to 1.8 (0.03 - 8.7) g/24 h (p = 0.012). Creatinine clearance remained stable (53 (29 - 160) ml/min at 3 months vs. 44 (29 - 159) at baseline). Until now, patients could be followed for a median of 3 (1 - 6) years. After 1 year, 21.4% (n = 3) had a complete response, 50.0% (n = 7) partial response. Two relapses occurred after 1 and 3.5 years. The presence of glomerulosclerosis before RTX was associated with a poorer outcome. Conclusions: The 4 x 4-weekly infusion of RTX is a reasonable option for the second- and third-line therapy of MN providing a better safety profile compared to other immunosuppressive treatments of MN.