Advancing Clinical Research in Primary Glomerular Diseases (UM1)

描述（由申请人提供）：肾小球疾病是全球终末期肾病（ESRD）的主要原因。有四种特发性疾病占大多数病例：伊加肾病（IgAN）、局灶节段性肾小球硬化（FSGS）、膜性肾病（MN）和微小病变病（MOD）。主要挑战包括这些疾病的相对罕见性、诊断不足和病因异质性（导致缺乏有效病例队列），以及复发-缓解型活动模式，平均进展速度缓慢，预后变异性高（需要长期随访数年至数十年）。这些疾病的治疗选择最近也很有限。最近在定义这四种疾病的关键疾病机制方面取得了进展，包括发现新的遗传易感性等位基因，新的循环因子和引发疾病的特定环境损伤。因此，本项目旨在开发一个由650例IgAN、FSGS、MN和MCD患者组成的纵向观察性队列（沿着650例种族和地理位置匹配的健康对照）。将以6个月的间隔对队列进行随访，前瞻性收集临床数据和生物材料，包括血液、尿液、唾液和粪便材料。这些数据和生物材料将促进临床、遗传学、生物化学和免疫学研究的整合 来推进肾小球疾病的研究作为该提案的一部分，我们建议进行一些创新的临床、遗传和生物标志物试点研究，这些研究将随着该队列的建立而变得可行。除了使强大的翻译研究，这种独特的资源也将提供宝贵的见解，这些疾病的自然史。该队列的发现也将为新的治疗性临床试验奠定基础，从而直接影响患者的护理。该提案汇集了一个经验丰富的研究人员团队，他们对肾小球疾病领域有相当大的贡献，包括哥伦比亚肾小球中心、哥伦比亚肾脏病理学部、哥伦比亚儿科肾脏病学部和Gaslini儿科研究所的成员。此外，我们的提议得到了行业、FDA和患者倡导团体的大力支持。

DESCRIPTION (provided by applicant): Glomerular diseases are responsible for a large fraction of end stage renal disease (ESRD) worldwide. There are four idiopathic disorders that account for the majority of cases: IgA nephopathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and minimal change disease (MOD). The major challenges include relative rarity, under-diagnosis, and etiologic heterogeneity of these disorders (resulting in the scarcity of well powered case cohorts), and relapsing-remitting patterns of activity with slow average rates of progression and high variability in prognosis (necessitating long-term follow up of several years to decades). Therapeutic options for these diseases are also recently limited. There has been recent progress in defining critical disease mechanisms for these four disorders, including discoveries of new genetic susceptibility alleles, novel circulating factors, and specific environmental insults inciting the disease. Accordingly, this project aims to develop a longitudinal observational cohort of 650 patients with IgAN, FSGS, MN and MCD (along with 650 ethnically and geographically matched healthy controls). The cohort will be followed at 6-month intervals with prospective collection of clinical data and biological materials, including blood, urine, saliva, and fecal material. These data and biomaterials will facilitate integration of clinical, genetic, biochemical, and immunologic studies to advance the science of glomerular disease. As part of this proposal, we suggest a number of innovative clinical, genetic, and biomarker pilot studies that would become feasible with the establishment of this cohort. In addition to enabling well-powered translational studies, this unique resource will also provide invaluable insights into the natural history of these disorders. The findings from this cohort will also lay basis for new therapeutic clinical trials, and thus wil directly impact the care of patients. The proposal brings together an experienced team of investigators with considerable contributions to the field of glomerular disease, including members of the Columbia Glomerular Center, Columbia Renal Pathology Division, Columbia Pediatric Nephrology Division, and the Gaslini Pediatric Institute. Moreover, our proposal has a considerable support from the industry, FDA, and patient advocacy groups.