Nephrotic Syndrome Rare Disease Clinical Research Network

描述（由申请人提供）：微小改变病（MCD）、局灶性和节段性肾小球硬化（FSGS）和膜性肾病（MN）是肾小球疾病，尽管罕见，但在ESRD中占很大比例。越来越多的人认为，目前采用的基于组织病理学的FSGS和MN分类是不充分的，因为它不是基于对这些疾病的分子基础的理解，也因为它不能很好地预测特定肾小球组织病理学分类中个体的异质性自然史或对治疗的反应。鉴于这些不足之处，我们对这些疾病的治疗方法不完善也就不足为奇了。我们建议，在对原发性非炎症性肾小球疾病进行更有效的介入研究之前，必须克服几个主要障碍。在这些障碍中，缺乏肾小球疾病的特异性生物标志物，这将允许对肾小球疾病组织病理学进行精确的、生物学相关的亚分类，这有助于确定临床研究中的受试者纳入和排除标准。这种疾病亚分类可能克服了研究人群异质性的影响，这种异质性可能对过去对这些肾小球疾病的研究有复杂的解释。新的肾小球疾病生物标志物也可能预测疾病的自然史，允许适当选择和预测对特定治疗干预的反应，允许早期发现疾病，或提供疾病活动的指标。重要的是，目前缺乏一个强大的调查基础设施来促进收集、培养和获取生物标志物鉴定所需的人类生物材料和相关临床数据，以确定临床相关研究终点，并开展试点临床研究，以推进MCD、FSGS和MN患者的护理。基于这些原因，我们建议建立肾病综合征RDCRN，这是一个多学科的研究和教育平台，汇集了临床和转化科学家以及两个非专业研究和患者教育基金会，旨在开始更好地研究和教育FSGS， MN和MCD患者。相关性（见说明）：MCD、FSGS和MN是导致严重发病率和高死亡率的罕见疾病，造成巨大的个人和社会经济负担。肾病综合征罕见病联盟的创建将提供一个易于获取的研究和教育资源，这将显著提高我们研究、分类、表征、诊断和治疗非炎症性肾小球疾病的能力。

DESCRIPTION (provided by applicant): Minimal Change Disease (MCD), Focal and Segmental Glomerulosclerosis (FSGS), and Membranous Nephropathy (MN) are glomerular diseases that despite their rarity, account for a large fraction of prevalent ESRD. There is growing consensus that the presently employed histopathology-based classification of FSGS and MN is inadequate because it is not based on an understanding of the molecular basis of these diseases, and because it does not well predict the heterogeneous natural history or response to therapy of individuals within a given glomerular histopathological category. Given these inadequacies, it is not surprising that our therapeutic approach to these diseases is imperfect. We propose that several major barriers must be overcome before more effective interventional studies of primary non-inflammatory glomerular disease can be conducted. Among these barriers is the absence of specific biomarkers of glomerular disease that would allow refined, biologically relevant sub-classification of glomerular disease histopathology useful for defining subject inclusion and exclusion criteria in clinical studies. Such disease sub-classification might overcome the effects of study population heterogeneity that likely have complicated interpretation of past studies of these glomerular diseases. New glomerular disease biomarkers might also predict disease natural history, allow proper selection of and prediction of response to specific therapeutic intervention, allow early detection of disease, or provide indicators of disease activity. Importantly, a robust investigative infrastructure is presently lacking that would facilitate collection, cultivation, and access to human biological material and associated clinical data necessary for biomarker identification, for the identification of clinically relevant study endpoints, and for conducting pilot clinical studies that would advance the care of MCD, FSGS, and MN patients. For these reasons, we propose the establishment of a Nephrotic Syndrome RDCRN, a multidisciplinary research and education platform that brings together clinical and translational scientists and two lay research and patient education foundations, aimed at beginning to better study and educate patients with FSGS, MN, and MCD. RELEVANCE (See instructions): MCD, FSGS, and MN are rare diseases that cause serious morbidity and high mortality, generating enormous individual and societal economic burden. Creation of the Nephrotic Syndrome Rare Disease Consortium will provide a readily accessible research and education resource that will significantly advance our ability to study, classify, characterize, diagnose, and treat non-inflammatory glomerular diseases.