Study B- cNEPTUNE

摘要 目前对儿童肾病综合征（NS）的治疗方法是基于常规的临床和实验室检查结果 无法准确定义潜在的生物学机制，预测临床过程，或选择最佳的 疗法儿童NS的治疗缺乏合理的机制基础，并与显著的发病率相关 在美国，12%的儿童终末期肾病是由它引起的。一种精确的医学方法 有必要确定机械离散的疾病亚组，完善生物标志物，以帮助分子 分类，确定相关的治疗目标，并改善儿科NS的试验设计。儿童 肾病综合征研究网络中的肾病综合征队列（队列B）包括16名入选者 儿科中心和相关研究者。在本项目中，队列B将扩大到200名发生事件的儿童， NS，前瞻性随访以确定纵向病程，收集生物标本， 用于治疗靶点鉴定的综合分子谱分析（表型、基因型、免疫谱分析）。 cNEPTUNE将开发和改进临床试验方法、终点和系统，以实现以下目标： 包括肾病综合征儿童在内的精准医学试验。在这项更新建议中，我们建议 (a)定义患有偶发NS的儿童的基因型-表型亚组;（B）定义非侵入性生物标志物， 包括免疫学特征;（c）鉴定候选治疗药物 基于机制定义的NS的目标;以及（d）开发经验证的终点、试验设计和系统 为NS患者促进高效和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.