Nephrotic Syndrome Rare Disease Clinical Research Network

描述（由申请人提供）：微小病变病 (MCD)、局灶性节段性肾小球硬化症 (FSGS) 和膜性肾病 (MN) 是肾小球疾病，尽管很少见，但占流行性 ESRD 的很大一部分。越来越多的共识认为，目前采用的基于组织病理学的 FSGS 和 MN 分类是不够的，因为它不是基于对这些疾病的分子基础的理解，并且因为它不能很好地预测给定肾小球组织病理学类别内个体的异质自然史或对治疗的反应。鉴于这些不足，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。这些障碍之一是缺乏肾小球疾病的特异性生物标志物，这些生物标志物可以对肾小球疾病组织病理学进行精细的、生物学相关的子分类，从而有助于定义临床研究中的受试者纳入和排除标准。这种疾病的子分类可能会克服研究人群异质性的影响，这种异质性可能会使对这些肾小球疾病的过去研究的解释变得复杂。新的肾小球疾病生物标志物还可以预测疾病自然史，允许正确选择和预测对特定治疗干预的反应，允许疾病的早期检测，或提供疾病活动的指标。重要的是，目前缺乏强大的研究基础设施，以促进收集、培养和获取生物标志物识别所需的人类生物材料和相关临床数据，确定临床相关研究终点，以及开展试点临床研究，以促进 MCD、FSGS 和 MN 患者的护理。出于这些原因，我们建议建立肾病综合征 RDCRN，这是一个多学科研究和教育平台，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（参见说明）：MCD、FSGS 和 MN 是罕见疾病，会导致严重的发病率和高死亡率，产生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易于获取的研究和教育资源，这将显着提高我们研究、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.