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我们在成人原发性肾小球肾炎的利妥昔单抗治疗方面的经验及文献复习。

Our experience with rituximab therapy for adult-onset primary glomerulonephritis and review of literature.

机构信息

Department of Nephrology and Transplantation, Royal Perth Hospital, Level 6 South Block, Perth, WA, 6000, Australia.

出版信息

Int Urol Nephrol. 2013 Jun;45(3):795-802. doi: 10.1007/s11255-012-0206-0. Epub 2012 Jul 15.

Abstract

BACKGROUND

B cell-targeted immunosuppression with rituximab as primary treatment or when conventional therapy is contraindicated or unsuccessful can induce remission in idiopathic membranous nephropathy (IMN). We explored the efficacy and safety of rituximab therapy in an adult population with IMN and other primary glomerulonephritides.

METHOD

This study is a single-centre retrospective case review of 24 adult patients who received rituximab (RTX) for IMN (n = 11), minimal change disease (MCD, n = 7), focal segmental glomerulosclerosis (FSGS, n = 4), and membranoproliferative glomerulonephritis (MPGN, n = 2). Outcomes included the proportion of patients with complete and partial remission, frequency of relapse, the amount of post-RTX immunosuppression, and toxicity.

RESULTS

The median follow-up for all patients was 31.5 months (IQR: 15.0-44.0). Rituximab therapy induced remission in 19/24 (79.2 %) patients (IMN: 63.6 %, MCD: 100 %, FSGS: 75 %, and MPGN: 100 %). Disease recurrence in patients with ≥ 3 relapses pre-RTX therapy (MCD, n = 6 and FSGS, n = 1) decreased from 37.0 to 19.6 events per 1,000 patient-months. All patients with steroid maintenance, discontinued or achieved at least a 50 % dose reduction at 3.0 months (IQR: 1.5-8.0) post-treatment. One patient ceased CSA in addition to a 50 % steroid dose reduction 13 months post-RTX. Rituximab was well tolerated with a single serious infection (4.2 %) responsive to treatment.

CONCLUSIONS

Rituximab induced remission in IMN comparable with published reports but had an additional benefit in inducing remission in other common glomerulonephritides. Additional randomized studies are needed to confirm its potential therapeutic benefit and optimal dosing for adult-onset primary glomerulonephritis.

摘要

背景

利妥昔单抗作为原发性治疗或在常规治疗禁忌或无效时靶向 B 细胞的免疫抑制可以诱导特发性膜性肾病(IMN)缓解。我们探索了利妥昔单抗治疗特发性膜性肾病(IMN)和其他原发性肾小球肾炎成人患者的疗效和安全性。

方法

这是一项单中心回顾性病例研究,纳入了 24 名接受利妥昔单抗(RTX)治疗的成人患者,其中 11 例为特发性膜性肾病(IMN),7 例为微小病变性肾病(MCD),4 例为局灶节段性肾小球硬化(FSGS),2 例为膜增殖性肾小球肾炎(MPGN)。结局包括完全缓解和部分缓解患者的比例、复发频率、RTX 后免疫抑制的剂量和毒性。

结果

所有患者的中位随访时间为 31.5 个月(IQR:15.0-44.0)。利妥昔单抗治疗诱导缓解的患者有 19/24(79.2%)(IMN:63.6%,MCD:100%,FSGS:75%,MPGN:100%)。在接受 RTX 治疗前至少有 3 次复发的患者(MCD,n=6;FSGS,n=1),疾病复发率从每 1000 患者-月 37.0 次降至 19.6 次。所有患者在治疗后 3.0 个月(IQR:1.5-8.0)停用或至少减少 50%的激素剂量。1 例患者在 RTX 治疗后 13 个月停用 CSA 并减少 50%的激素剂量。利妥昔单抗耐受性良好,仅发生 1 例严重感染(4.2%),经治疗后得到控制。

结论

利妥昔单抗诱导 IMN 缓解的疗效与已发表的报告相当,但在诱导其他常见肾小球肾炎缓解方面具有额外的益处。需要进一步的随机研究来证实其对成人原发性肾小球肾炎的潜在治疗益处和最佳剂量。

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