Randomized, Controlled Trial of Prednisone, Cyclophosphamide, and Cyclosporine in Lupus Membranous Nephropathy
Randomized, Controlled Trial of Prednisone, Cyclophosphamide, and Cyclosporine in Lupus Membranous Nephropathy
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DOI：
10.1681/asn.2008060665
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发表时间：
2009-04-01
影响因子：
13.6
通讯作者：
Balow, James E.
中科院分区：
文献类型：
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作者：
Austin, Howard A., III;Illei, Gabor G.;Balow, James E.
狼疮性膜性肾病（LMN）患者长期存在与包括终末期肾病在内的迁延性肾病综合征相关的发病率和死亡率风险。这种情况的最佳治疗方法是有争议的。42例LMN患者参加了一项随机对照试验，以比较连续免疫抑制药物与单独泼尼松。辅助治疗方案包括环孢素（CsA）11个月或隔月静脉冲击环磷酰胺（IVCY）6剂;对照组仅接受隔日泼尼松。中位蛋白尿为5.4 g/d（范围为2.7 - 15.4 g/d）。我们通过单变量生存分析评估了主要结局，即12个月方案中蛋白尿缓解的时间。在1年时，泼尼松的累积缓解概率为27%，IVCY为60%，CsA为83%。虽然IVCY和CsA在诱导蛋白尿缓解方面比泼尼松更有效，但CsA完成后肾病综合征复发的发生率明显高于IVCY。通过多变量生存分析，泼尼松治疗和高级别蛋白尿（> 5 g/d）与缓解概率降低独立相关，而与人种或种族无关。12个月方案期间的不良反应包括胰岛素依赖性糖尿病（泼尼松组1例，CsA组2例）、肺炎（泼尼松组1例，CsA组2例）和局部带状疱疹（IVCY组2例）。总之，在LMN患者中，含CsA或IVCY的治疗方案在诱导蛋白尿缓解方面均比单用泼尼松更有效。
Patients with lupus membranous nephropathy (LMN) are at substantial long-term risk for morbidity and mortality associated with protracted nephrotic syndrome, including ESRD. The optimal treatment for this condition is controversial. Forty-two patients with LMN participated in a randomized, controlled trial to compare adjunctive immunosuppressive drugs with prednisone alone. Adjunctive regimens included either cyclosporine (CsA) for 11 mo or alternate-month intravenous pulse cyclophosphamide (IVCY) for six doses; the control group received alternate-day prednisone alone. Median proteinuria was 5.4 g/d (range 2.7 to 15.4 g/d). We assessed the primary outcome, time to remission of proteinuria during the 12-mo protocol, by univariate survival analysis. At 1 yr, the cumulative probability of remission was 27% with prednisone, 60% with IVCY, and 83% with CsA. Although both IVCY and CsA were more effective than prednisone in inducing remissions of proteinuria, relapse of nephrotic syndrome occurred significantly more often after completion of CsA than after IVCY. By multivariate survival analysis, treatment with prednisone and high-grade proteinuria (> 5 g/d) but not race or ethnicity were independently associated with a decreased probability of remission. Adverse effects during the 12-mo protocol included insulin-requiring diabetes (one with prednisone and two with CsA), pneumonia (one with prednisone and two with CsA), and localized herpes zoster (two with IVCY). In conclusion, regimens containing CsA or IVCY are each more effective than prednisone alone in inducing remission of proteinuria among patients with LMN.