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。特发性疾病主要有四种：IgA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、诊断不足和病原学异质性(导致缺乏强有力的病例队列)，以及复发-缓解活动模式，平均进展速度慢，预后变异性高(需要几年至几十年的长期随访)。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，包括发现了新的遗传易感等位基因、新的循环因素和引发疾病的特定环境侮辱。因此，该项目旨在建立一个包括650名IgAN、FSGS、MN和MCD患者(以及650名种族和地理上匹配的健康对照)的纵向观察队列。队列将每隔6个月进行一次跟踪，预期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、生化和免疫学研究的整合。 以促进肾小球疾病的科学研究。作为这项建议的一部分，我们建议进行一些创新的临床、遗传和生物标记物试点研究，这些研究将随着这个队列的建立而变得可行。除了能够进行强大的翻译研究外，这一独特的资源还将提供对这些疾病的自然历史的宝贵见解。这一队列的发现也将为新的治疗临床试验奠定基础，因此将直接影响患者的护理。该提案汇集了一支在肾小球疾病领域做出重大贡献的经验丰富的研究团队，其中包括哥伦比亚肾小球中心、哥伦比亚肾脏病理科、哥伦比亚儿科肾病科和加斯利尼儿科研究所的成员。此外，我们的建议得到了业界、FDA和患者倡导团体的相当大的支持。

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.