Advancing Clinical Research in Primary Glomerular Diseases (UM1)

描述（由申请人提供）：肾小球疾病是世界范围内终末期肾病（ESRD）的主要原因。有四种特发性疾病占大多数病例：IgA肾病（IgAN），局灶节段性肾小球硬化（FSGS），膜性肾病（MN）和最小变化病（MOD）。主要的挑战包括这些疾病的相对罕见、诊断不足和病因异质性（导致缺乏良好的病例队列），以及复发-缓解型活动，平均进展速度慢，预后多变性（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。最近在确定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害。因此，该项目旨在建立一个纵向观察队列，包括650名IgAN、FSGS、MN和MCD患者（以及650名种族和地理匹配的健康对照）。该队列将每隔6个月进行随访，收集临床数据和生物材料，包括血液、尿液、唾液和粪便。这些数据和生物材料将促进临床、遗传、生化和免疫学研究的整合

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.