Study B- cNEPTUNE

摘要 目前治疗儿童肾病综合征(NS)的方法是基于常规的临床和实验室检查结果 不能准确定义潜在的生物机制，预测临床过程，或选择最佳的 心理治疗。儿童NS的治疗缺乏合理的机制基础，并与显著的发病率相关 占美国儿童终末期肾病的12%。一种精准医学方法 有理由识别机械上离散的疾病亚组，提炼生物标记物以协助分子 对儿童NS进行分类，确定相关治疗靶点，改进试验设计。孩子们的 肾病综合征研究网络中的肾病综合征队列(队列B)包括16个登记 儿科中心和相关调查人员。在这个项目中，队列B将扩大到200名有意外事件的儿童 NS，前瞻性地跟踪定义纵向病程，收集生物标本以使 全面的分子图谱(表型、基因、免疫图谱)，用于识别治疗靶点。 CNEPTUNE将开发和改进临床试验方法、终点和系统，以使 包括肾病综合征儿童在内的精准医学试验。在这项续期建议中，我们建议 (A)确定患有NS的儿童的基因型-表型亚组；(B)定义非侵入性生物标记物， 包括免疫学概况，在功能上定义的NS亚组；(C)确定候选治疗方案 基于机械定义的NS的目标；以及(D)开发经过验证的终端、试验设计和系统 为NS患者培育高效、有效的精准医学临床试验。

ABSTRACT Current approaches to childhood nephrotic syndrome (NS) are based on routine clinical and laboratory findings that are unable to accurately define the underlying biologic mechanisms, predict clinical course, or select optimal therapy. Treatment of childhood NS lacks a rational mechanistic basis and is associated with significant morbidity and is responsible for 12% of the pediatric end stage kidney disease in the USA. A precision medicine approach is warranted to identify mechanistically discrete disease subgroups, refine biomarkers to assist with molecular classification, identify relevant treatment targets, and improve trial design for pediatric NS. The children's nephrotic syndrome cohort in the Nephrotic Syndrome Study Network (Cohort B) is inclusive of 16 enrolling pediatric centers and associated investigators. In this project, Cohort B will expand to 200 children with incident NS, prospectively followed to define the longitudinal disease course, collect biospecimens to enable comprehensive molecular profiling (phenotype, genotype, immune profiling) for treatment target identification. cNEPTUNE will develop and improve clinical trial methods, endpoints, and systems to enable the conduct of precision medicine trials inclusive of children with nephrotic syndrome. In this renewal proposal, we propose to (a) define genotype-phenotype subgroups of children with incident NS; (b) define non-invasive biomarkers, inclusive of immunological profiles, in functionally defined subgroups of NS; (c) identify candidate therapeutic targets based on the mechanistically defined NS; and (d) develop validated endpoints, trial designs, and systems to foster efficient and effective precision medicine clinical trials for patients with NS.