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(FSGS)是一种对免疫调节剂反应差、预后差的器官特异性自身免疫性疾病。患有FSGS的儿童和年轻人数量相对较少，缺乏令人信服的前瞻性、双盲、随机、多中心治疗研究，阻碍了循证治疗方法的形成。环磷酰胺和钙调神经磷酸酶抑制剂作用于细胞毒性T细胞周期的不同部位，并支持联合治疗协同疗效的假说。我们提出了一项双盲、随机、对照试验，比较A)环磷酰胺、他克莫司和口服类固醇，以及血管紧张素转换酶抑制剂(ACEI)和B)他克莫司、口服类固醇和ACEI。我们将开发一个数据库，以比较每个治疗组在主要终点：减少蛋白尿方面的反应。次要结果将是缓解率、复发频率、通过肾小球滤过率、总累积皮质类固醇剂量和不良事件衡量的肾功能衰竭进展。患者的年龄、种族、性别、肾组织学分类、podocin突变状态、基线蛋白尿和基线肾脏排泄功能将与原发和继发结局相关。我们已经组成了一个由28个儿科中心组成的西部儿科肾病临床试验小组，与成人肾科医生合作。这些中心过去有成功的合作研究的丰富历史。从我们过去两年对患者的初步调查来看，我们有足够的患者人口基础来进行招聘，以确保在我们地区至少招收100名研究对象。我们将作为区域中心参与合作的多中心随机对照治疗临床试验，以改善RFA中所述患有原发FSGS的儿童和年轻人的临床病程。

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.