Immunosuppressive drug therapy in lupus membranous nephropathy

这是一项2期随机对照试验，旨在评估免疫抑制药物治疗狼疮膜性肾病的有效性和毒性。肾活检证实的膜性肾病患者均接受隔日强的松治疗，随机分为3组：1.不加用药(对照组)；2.环磷酰胺每隔月静脉注射至1.0g/m2体表面积，共6次；或3.口服环孢素200 mg/m2，共11个月。肾小球滤过率为25~66ml/min/1.73m2的患者被随机分为单用泼尼松组或泼尼松加环磷酰胺组。在整个研究过程中监测肾功能和疾病活动；在研究开始时和研究结束时检查肾小球功能的生理指标(肾小球滤过率和有效肾血浆流量)。比较各治疗组肾小球功能良好结果的数量和药物相关毒性反应。环磷酰胺和环孢素在诱导蛋白尿缓解方面均优于单用隔日强的松。在完成环孢素治疗后，重度蛋白尿的复发明显多于环磷酰胺治疗。对单用强的松或环孢素耐药或复发的10例患者，每隔一个月静脉注射环磷酰胺治疗1年，然后每季度静脉注射环磷酰胺，中位疗程为2年。6例部分缓解，2例蛋白尿完全缓解。我们已经发表了对治疗结果的分析，以及对影响这些患者结果的人口统计学和临床因素的详细多变量分析。这项研究仍在积极进行，以促进对研究数据和标本的进一步分析。

This is a phase 2 randomized controlled trial to evaluate the effectiveness and toxicity of immunosuppressive drug therapy in patients with lupus membranous nephropathy. Patients with renal biopsy documented membranous nephropathy were all treated with alternate day prednisone and were randomized to receive: 1. no additional therapy (control group), 2. intravenous cyclophosphamide up to 1.0 gm per m2 body surface area every other month for 6 total doses, or 3. oral cyclosporine up to 200 mg per m2 body surface area for a total of 11 months. Patients with glomerular filtration rates 25 to 66 ml/min/1.73 m2 body surface area were randomized only to prednisone alone or to prednisone plus cyclophosphamide. Renal function and disease activity were monitored throughout the study; physiologic measures of glomerular function (glomerular filtration rate and effective renal plasma flow) were examined at study entry and at the conclusion of the study. Comparison was made of the number of favorable outcomes of glomerular function as well as drug related toxicities observed within each treatment group. Both adjunctive cyclophosphamide and cyclosporine were more effective than alternate day prednisone alone in inducing remissions of proteinuria. Relapse of high-grade proteinuria occurred significantly more often after completing cyclosporine than after cyclophosphamide. Ten patients, who were resistant to or relapsed after prednisone alone or cyclosporine, were treated with intravenous cyclophosphamide every other month for a year, followed by quarterly pulse intravenous cyclophosphamide for a median duration of 2 years. Six patients achieved a partial remission and 2 achieved a complete remission of proteinuria. We have published the analysis of the treatment outcomes as well as a detailed multivariate analysis of the demographic and clinical factors that impact the outcomes of these patients. The study remains active to facilitate additional analyses of study data and specimens.