Focal Segmental Glomerulosclerosis in Young Patients

描述（由申请人提供）： 原发性局灶节段性肾小球硬化症（FSGS）是一种器官特异性自身免疫性疾病，对免疫调节剂反应不良，预后不良。相对较少的儿童和年轻成人与FSGS和缺乏令人信服的前瞻性双盲随机多中心治疗研究，阻碍了制定一个循证治疗方法。环磷酰胺和钙调磷酸酶抑制剂作用于细胞毒性T细胞周期的不同位点，支持联合治疗协同有效性的假设。我们提出了一项双盲、随机、对照试验，比较A）环磷酰胺序贯给药后他克莫司联合口服类固醇和血管紧张素转换酶抑制剂（ACEI）与B）他克莫司联合口服类固醇和ACEI。我们将建立一个数据库，比较每个治疗组在主要终点（蛋白尿减少）方面的反应。次要结局将是缓解率、复发频率、通过肾小球滤过率测量的肾衰竭进展、皮质类固醇累积总剂量和不良事件。患者年龄、种族、性别、肾组织学分类、podocin突变状态、基线蛋白尿和基线肾排泄功能将与主要和次要结局相关。我们已经成立了一个西方儿科肾脏病临床试验组，由28个儿科中心与合作的成人肾脏病学家组成。这些中心在过去有着丰富的成功合作研究历史。从我们过去两年的初步患者调查来看，我们有足够的患者人群基础进行招募，以确保在我们地区招募至少100例研究受试者。我们将作为区域中心参与合作、多中心随机对照临床试验，以改善RFA中所述原发性FSGS儿童和年轻成人的临床病程。

DESCRIPTION (provided by applicant): Primary focal segmental glomerulosclerosis (FSGS) is an organ-specific autoimmune disease with poor response to immunomodulating agents and a poor prognosis. The relatively small number of children and young adults with FSGS and the lack of compelling prospective double-blind randomized multi-center therapeutic studies have hampered the formulation of an evidenced-based therapeutic approach. Cyclophosphamide and calcineurin inhibitors act on different sites of the cytotoxic T cell cycle and support the hypothesis of synergistic effectiveness of combination therapy. We propose a double-blind, randomized, controlled trial comparing A) sequential cyclophosphamide followed by tacrolimus with oral steroids and angiotensin-converting enzyme inhibitors (ACEI) with B) tacrolimus with oral steroids and ACEI. We will develop a database to compare the response to each treatment arm with respect to the primary end-point: reduction in proteinuria. The secondary outcomes will be remission rate, relapse frequency, progression of renal failure as measured by glomerular filtration rate, total cumulative corticosteroid dose and adverse events. Patient age, ethnicity, gender, renal histological classification, podocin mutation status, baseline proteinuria and baseline renal excretory function will be correlated with primary and secondary outcomes. We have formed a Western Pediatric Nephrology Clinical Trials Group consisting of 28 pediatric centers with collaborating adult nephrologists. These centers have a rich history of successful collaborative studies in the past. From our initial survey of patients in the past two years, we have a more than sufficient patient population-base from which to recruit to ensure enrollment of at least 100 study subjects in our region. We will participate as a regional center in the collaborative, multicenter randomized controlled clinical trial of therapy to improve the clinical course of children and young adults with primary FSGS as stated in the RFA.