Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate
Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate
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DOI：
10.1093/ndt/gfh036
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发表时间：
2004-05-01
影响因子：
6.1
通讯作者：
Wetzels, JFM
中科院分区：
文献类型：
--
作者：
du Buf-Vereijken, PWG;Branten, AJW;Wetzels, JFM
背景特发性膜性肾病（iMN）和肾功能不全患者进展为终末期肾病（ESRD）的风险较高。在短期内，口服环磷酰胺和类固醇治疗减轻了这些患者的肾功能恶化;然而，长期疗效尚不清楚。我们前瞻性研究了65例iMN和肾功能不全（血清肌酐> 135 mumol/l）患者，这些患者接受口服环磷酰胺（1.5 - 2.0 mg/kg/d，持续12个月）和类固醇（甲基强的松龙脉冲3 x 1 g，静脉注射，第1、3和5个月，口服强的松0.5 mg/kg/48 h，持续6个月）治疗。随访51（5 - 132）个月。所有患者的肾功能暂时改善或稳定。部分缓解（PR）56例，完全缓解（CR）17例。在随访期间，11例患者复发（5年后复发率为28%），其中9例因肾功能恶化而重新治疗。在随访结束时，16例患者达到CR，31例患者达到PR，8例患者患有持续性肾病综合征，1例患者出现轻度蛋白尿，4例患者进展为ESRD，5例患者死亡。5年后的总体肾脏存活率为86%，7年后为74%，而历史对照组的5年和7年后为32%。三分之二的患者发生了与治疗相关的并发症，主要包括骨髓抑制和感染。1例患者发生膀胱癌，另1例患者发生前列腺癌。如果iMN和肾功能不全患者接受口服环磷酰胺治疗，肾脏生存率良好。然而，在较长的随访期间，副作用频繁发生，复发率高。
Background. Patients with idiopathic membranous nephropathy (iMN) and renal insufficiency have a high risk for progression to end-stage renal disease (ESRD). In the short term, treatment with oral cyclophosphamide and steroids attenuates the deterioration of renal function in these patients; however, the long-term efficacy is unknown.Methods. We have studied prospectively 65 patients with iMN and renal insufficiency (serum creatinine > 135 mumol/l) who were treated with oral cyclophosphamide (1.5-2.0 mg/kg/day for 12 months) and steroids (methylprednisolone pulses 3 x 1 g, i.v. at months 1, 3 and 5, and oral prednisone 0.5 mg/kg/48 h for 6 months).Results. Follow-up was 51 (5-132) months. Renal function temporarily improved or stabilized in all patients. A partial remission (PR) occurred in 56 patients followed by a complete remission (CR) in 17. During follow-up, 11 patients had relapsed (28% relapse rate after 5 years), of whom nine were re-treated because of renal function deterioration. At the end of follow-up, 16 patients were in CR, 31 in PR, eight had a persistent nephrotic syndrome, one had mild proteinuria, four had progressed to ESRD and five had died. Overall renal survival was 86% after 5 years and 74% after 7 years, compared with 32% after 5 and 7 years in a historical control group. Treatment-related complications occurred in two-thirds of patients, mainly consisting of bone marrow depression and infections. One patient has developed bladder cancer, another patient prostate cancer.Conclusions. Renal survival is good if patients with iMN and renal insufficiency are treated with oral cyclophosphamide. However, side effects occur frequently and relapse rate is high during longer follow-up.