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，用于评估狼疮膜肾病患者免疫抑制药物治疗的有效性和毒性。 肾脏活检记录的膜性肾病的患者均接受替代日泼尼松的治疗，并随机接受：1。静脉内（对照组），2。静脉内环磷酰胺高达1.0 gm，每M2每M2的每隔一个月，每隔一个月，总剂量为6个月份，或者总剂量为6个月，或者3。Oral Cyclosporine for 200 mg to 200 m2 mg 2 m2 mg 2 mg 2个月份。 肾小球滤过率25至66 mL/min/1.73 m2的身体表面积仅随机分为泼尼松或泼尼松加环磷酰胺的患者。 在整个研究过程中监测肾功能和疾病活性。在研究进入和研究结束时检查了肾小球功能（肾小球滤过率和有效肾脏血浆流量）的生理测量。 比较肾小球功能的有利结果以及每个治疗组中观察到的与药物相关的毒性进行了比较。 辅助环磷酰胺和环孢菌素都比单独诱导蛋白尿的替代白天泼尼松更有效。 在完成环孢菌素后，高度蛋白尿的复发比环磷酰胺后发生的频率要高得多。 十名单独泼尼松或环孢菌素后耐药或复发的患者每隔一个月用静脉注射环磷酰胺治疗一年，然后进行季度脉搏静脉静脉静脉环磷酰胺2年的持续时间。 六名患者已得到部分缓解，2例完全缓解了蛋白尿。 我们已经发布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​​因素的详细多元分析。 该研究仍然有效，以促进对研究数据和标本的其他分析。