Tacrolimus vs Intensive Prednisone in Pediatric FSGS

描述(由申请人提供)： 局灶性节段性肾小球硬化(FSGS)是儿童慢性肾脏疾病的主要原因。这种肾小球病变在少数人群中更为常见，并经常在移植肾中复发。尽管在分子遗传学方面取得了特别的进展，但这种情况的原因和最佳治疗仍然不清楚。对患有FSGS的成人进行的非对照研究支持长期使用强的松治疗。儿童的初步数据表明，钙调神经磷酸酶抑制剂他克莫司对其他疗法无效的患者可能有效。这项多中心研究的目的是比较他克莫司和强的松强化治疗在预防原发性FSGS进展方面的相对疗效。这是对这两种有希望的治疗方法在FSGS儿童中的首次对照评估。我们建议进行一项随机、开放的临床试验，对象是口服泼尼松4周无效且肾活检发现FSGS的肾病症性蛋白尿患者。患者将被分配接受每日泼尼松(60 mg/m2)治疗3个月，然后隔日服用泼尼松(40 mg/m2)15个月，或他克莫司加小剂量隔日(10 mg/m2)治疗18个月。此外，患者将接受最佳剂量的氯沙坦和阿托伐他汀，以控制蛋白尿、高血压和高脂血症。主要的结果指标将是：蛋白尿完全或部分缓解，保留肾小球滤过率，防止肾疤痕形成。次要结果指标将包括反应与一种新的组织病理学分类的相关性，由中心核心病理学小组评估。研究设计将纳入在数据协调中心和NIDDK指导委员会的指导下收集和储存可能重要的生物样本。儿童局灶性节段性肾小球硬化东部区域研究小组将由41个地点组成，由阿尔伯特·爱因斯坦医学院蒙特菲奥里医学中心区域协调中心指导。该项目预计将：1)改善FSGS儿童的预后，2)创建一个全国性的临床研究网络，促进未来在儿科肾病领域，特别是FSGS领域的基础和临床研究。

DESCRIPTION (provided by applicant): Focal Segmental Glomerulosclerosis (FSGS) is a major cause of chronic kidney disease in childhood. This glomerulopaty is more frequent in minority populations, and often recurs in the transplanted kidney. Despite advances particulary in molecular genetics, the cause and optimal treatment of this condition remains poorly defined. Uncontrolled studies in adults with FSGS support the use of prolonged prednisone therapy. Preliminary data in children suggests that the calcineurin inhibitor tacrolimus may be efficacious in patients who have been refractory to other therapies. The purpose of this multicenter study is to compare the relative efficacy of tacrolimus with that of intensive prednisone therapy in preventing the progression of primary FSGS. This represents the first controlled evaluation of these two promising therapies in children with FSGS. We are proposing a randomized, open-label clinical trial in patients with nephrotic range proteinuria who fail to respond to 4 weeks of oral prednisone and who are found to have FSGS on renal biopsy. Patients will be assigned to receive daily prednisone (60 mg/m2) for 3 months followed by either alternate day prednisone (40 mg/m2) for the ensuing 15 months or tacrolimus plus low-dose alternate day (10 mg/m2) for 18 months. In addition, patients will receive optimal doses of losartan and atorvostatin to control proteinuria, hypertension, and hypelipidemia. The primary outcome indicators will be: complete or partial remission of proteinuria, preservation of glomerular filtration rate, and prevention of renal scarring. Secondary outcome indicators will include correlation of response with a novel histopathologic classification, assessed by a centrol core pathology group. The study design will incorporate collection and storage of potentially important biological samples at the direction of the Data Coordinating Center and the Steering Committee of the NIDDK. The Eastern Regional Group for the Study of Focal Segmental Glomerulosclerosis in Children will be comprised of 41 sites under the direction of the Regional Coordinating Center at Montefiore Medical Center of the Albert Einstein College of Medicine. This project is expected to: 1) improve the outcome of children with FSGS, and, 2) create a nationwide network of clinical investigators that will facilitate future basic and clinical research in the field of pediatric nephrology, in general, and FSGS, in particular.