Immunosuppressive drug therapy in lupus membranous nephropathy

狼疮膜性肾病的免疫抑制药物治疗

• 批准号: 9148816
• 负责人: James Balow
• 金额: $ 31.1万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9148816
• 关键词: Accounting; Address; Adrenal Cortex Hormones; Alkylating Agents; Antiphospholipid Antibodies; Azathioprine; Biopsy; Body Surface Area; Clinical; Control Groups; Cyclophosphamide; Cyclosporine; Data; Deterioration; Disease remission; Dose; Effective Renal Plasma Flow; Effectiveness; Evolution; Glomerular Filtration Rate; Histologic; Immunosuppressive Agents; Incidence; Intravenous; Kidney; Kidney Diseases; Kidney Failure; Lupus; Lupus Nephritis; Measures; Membranous Glomerulonephritis; Monitor; Morbidity - disease rate; Multivariate Analysis; Myocardial Infarction; Nephrotic Syndrome; Oral; Outcome; Partial Remission; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiologic pulse; Physiological; Predictive Value; Prednisone; Prognostic Factor; Proteinuria; Publishing; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Relapse; Renal function; Reporting; Resistance; Risk; Safety; Specimen; Systemic Lupus Erythematosus; Therapeutic; Toxic effect; Treatment Protocols; Treatment outcome; base; clinically significant; design; glomerular function; mortality; mycophenolate mofetil; patient population; prospective

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.

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患者的有效性和毒性。 肾活检证实膜性肾病的患者均接受隔日泼尼松治疗，并随机接受：1. 不进行额外治疗（对照组），2. 每隔一个月静脉注射环磷酰胺，剂量为每平方米体表面积 1.0 gm，共 6 剂，或 3. 口服环孢素至每平方米体表面积 200 毫克，总共 11 个月。 肾小球滤过率 25 至 66 ml/min/1.73 m2 体表面积的患者被随机分配至单独使用泼尼松或泼尼松加环磷酰胺。 在整个研究过程中监测肾功能和疾病活动性；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）。 对每个治疗组内观察到的肾小球功能良好结果以及药物相关毒性的数量进行了比较。 辅助环磷酰胺和环孢素在诱导蛋白尿缓解方面比单独使用隔日泼尼松更有效。 完成环孢素治疗后重度蛋白尿复发的发生率明显高于环磷酰胺治疗后的复发率。 10 名对单用泼尼松或环孢素耐药或复发的患者，每隔一个月接受静脉注射环磷酰胺治疗，持续一年，然后每季度静脉注射环磷酰胺一次，中位持续时间为 2 年。 6 名患者蛋白尿部分缓解，2 名患者蛋白尿完全缓解。 我们发表了治疗结果的分析以及影响这些患者结果的人口统计和临床因素的详细多变量分析。 该研究仍然活跃，以促进对研究数据和样本的进一步分析。