Nephrotic Syndrome Study Network

Pro non-inflammatory glomerular diseases, including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN), account for approximately 15% of prevalent end-stage renal disease (ESRD) cases in the United States. Development of successful therapeutic interventions is hindered by a limited knowledge of underlying glomerular disease mechanisms. In response to the need for research concerning these conditions, the Nephrotic Syndrome Study Network (NEPTUNE) was established to investigate the underlying disease mechanisms, elucidate pathogenesis, and identify therapeutic targets for clinical trials. The NEPTUNE cohort study, one of the projects initiated by the consortium, is a prospective, observational study that enrolls children and adults with FSGS, MCD, and MN. In the first funding cycle, NEPTUNE recruited more than 500 rigorously phenotyped NS participants. In the second funding cycle, NEPTUNE will add 150 adults with NS at the time of diagnostic kidney biopsy enriched for individuals at high risk for adverse health outcomes (African ancestry and proteinuria >1.5 gm/day) and 120 children with NS at presentation and prior to biopsy. These cohorts will add critical segments of NS disease phenotypes to reflect the full NS disease spectrum in NEPTUNE. At baseline, NEPTUNE collects information on demographics, clinical history, physical examination, as well as tissue samples from a renal biopsy visit, blood and urine samples. Questionnaires are given to assess quality of life and self-reported health. Participants are assigned into a specific study cohort (FSGS, MCD, MN) based on renal biopsy. After baseline assessment is complete, participants are followed over 30 months to collect data concerning health, quality of life, and outcomes, and urine and blood samples. The NEPTUNE consortium banks the long-term observational data and corresponding biological specimens for future studies. NEPTUNE provides high-resolution clinical phenotypes of patients which are related to genome wide analyses to molecularly define disease categories, outcome predictors and therapeutic targets. The primary outcome is a composite measure of change in urinary protein excretion and change in renal function. Secondary outcome measures include quality of life assessment, development of new-onset diabetes, malignancies, infections, thromboembolic events, hospitalization, acute kidney injury, and death. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and histologic data for systems biology analysis. The whole genome sequencing (WGS) data generated from the NEPTUNE study can be accessed through dbGaP, accession number <a href = "https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs003210.v1.p1" target="_blank" rel="noopener noreferrer">phs003210.v1.p1</a>. The RNAseq data generated can be accessed through GEO, accession numbers <a href = "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE219185" target="_blank" rel="noopener noreferrer">GSE219185</a> and <a href = "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197307" target="_blank" rel="noopener noreferrer">GSE197307</a>. This study is ongoing.非炎症性肾小球疾病，包括微小病变性肾病（minimal change disease, MCD）、局灶节段性肾小球硬化（focal and segmental glomerulosclerosis, FSGS）及膜性肾病（membranous nephropathy, MN），在美国约占现患终末期肾病（end-stage renal disease, ESRD）病例的15%。由于对这类肾小球疾病的潜在发病机制认知有限，成功开发治疗干预手段的进程受到阻碍。为满足此类疾病相关研究的需求，肾病综合征研究网络（Nephrotic Syndrome Study Network, NEPTUNE）应运而生，旨在探究潜在发病机制、阐明疾病发病机制，并为临床试验确定治疗靶点。 作为该联盟发起的项目之一，NEPTUNE队列研究是一项前瞻性观察性研究，招募患有FSGS、MCD及MN的儿童与成人。在首个资助周期内，NEPTUNE已招募超过500名经过严格表型分型的肾病综合征（nephrotic syndrome, NS）参与者。在第二个资助周期中，NEPTUNE将新增150名确诊时已接受肾脏活检的成人NS患者，该队列富集了不良健康结局高风险人群（非洲血统且尿蛋白＞1.5g/天），同时新增120名在确诊时、肾脏活检前的儿童NS患者。上述队列将补充肾病综合征疾病表型的关键细分类型，以全面覆盖NEPTUNE研究中的肾病综合征疾病谱。 在基线阶段，NEPTUNE会收集参与者的人口学信息、临床病史、体格检查数据，以及肾脏活检时获取的组织样本、血液与尿液样本。同时发放问卷以评估参与者的生活质量与自我报告健康状况。参与者将根据肾脏活检结果被分配至特定研究队列（FSGS、MCD或MN）。基线评估完成后，研究将对参与者进行为期30个月的随访，收集其健康状况、生活质量、转归相关数据，以及尿液与血液样本。NEPTUNE联盟将长期留存该观察性数据与对应的生物样本，以供未来研究使用。NEPTUNE可为患者提供高分辨率的临床表型数据，这类数据可与全基因组分析相结合，以分子层面定义疾病分类、预后预测因子及治疗靶点。主要结局指标为尿蛋白排泄量变化与肾功能变化的复合指标。次要结局指标包括生活质量评估、新发糖尿病、恶性肿瘤、感染、血栓栓塞事件、住院、急性肾损伤及死亡。分子谱与基因表达数据将与表型、遗传及组织学数据相结合，用于系统生物学分析。 本研究产生的全基因组测序（whole genome sequencing, WGS）数据可通过dbGaP获取，登录编号为<a href = "https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs003210.v1.p1" target="_blank" rel="noopener noreferrer">phs003210.v1.p1</a>。产生的RNA测序（RNAseq）数据可通过GEO获取，登录编号分别为<a href = "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE219185" target="_blank" rel="noopener noreferrer">GSE219185</a>与<a href = "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197307" target="_blank" rel="noopener noreferrer">GSE197307</a>。 本研究仍在进行中。