Primary Outcomes in Glomerulonephritis Study (PROGRESS)

描述(申请人提供)：微小病变(MCD)、局灶性和节段性肾小球硬化(FSGS)、膜性肾病(MN)和IgA肾病(IgAN)是肾小球疾病，尽管罕见，但在流行的肾小球疾病中占很大比例 ESKD。现在的共识是，目前使用的基于组织病理学的这些疾病的分类是不充分的，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类别中的个体的异质性自然病史或对治疗的反应。我们建议，在对原发慢性肾小球疾病进行更有效的介入研究之前，或者在这些疾病的患者得到适当的诊断和治疗之前，必须克服主要障碍。这些障碍之一是缺乏具有良好特征的肾小球疾病的特定生物标记物，这些标记物将允许对肾小球疾病组织病理学进行精细的、生物学上相关的亚分类。这样的疾病分类可能会克服肾小球疾病人群的异质性的影响，这可能会对过去对这些肾小球疾病的研究进行复杂的解释。新的肾小球疾病生物标志物还可能预测疾病的自然病史，允许适当地选择和预测对特定治疗干预的反应，允许及早发现疾病，或者提供疾病活动的指标。重要的是，强大的调查基础设施将有助于 收集、培养和获取生物标记物鉴定所需的人体生物材料和相关临床数据，开发可用作治疗试验终点的评估患者报告结果(PRO)的工具，以及进行试验性临床研究，以促进对MCD、FSGS、MN、IgAN患者的护理。出于这些原因，我们建议建立一个参与的临床中心(PCC)，将临床和翻译科学家聚集在一起，建立一个基础研究基金会， 以及来自私营部门的合作伙伴，作为更大的慢性肾小球疾病研究联盟的合作者，研究MCD、FSGS、MN和IgAN患者。

DESCRIPTION (provided by applicant): Minimal Change Disease (MCD), Focal and Segmental Glomerulosclerosis (FSGS), Membranous Nephropathy (MN), and IgA Nephropathy (IgAN) are glomerular diseases that despite their rarity, account for a large fraction of prevalent ESKD. There is now consensus that the presently employed histopathologybased classification of these diseases 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. We propose that major barriers must be overcome before more effective interventional studies of primary chronic glomerular disease can be conducted or before patients suffering from these diseases can be properly diagnosed and treated. Among these barriers is the absence of well characterized specific biomarkers of glomerular disease that would allow refined, biologically relevant sub-classification of glomerular disease histopathology. Such disease sub-classification might overcome the effects of glomerular disease 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 would facilitate collection, cultivation, and access to human biological material and associated clinical data necessary for biomarker identification, for developing instruments useful for evaluating patient reported outcomes (PRO) that might be useful as endpoints in therapeutic trials, and for conducting pilot clinical studies that would advance the care of MCD, FSGS, MN, IgAN patients. For these reasons, we propose the establishment of PROGRESS, a Participating Clinical Center (PCC) that brings together clinical and translational scientists, a lay research foundation, and partners from the private sector to study patients with MCD, FSGS, MN and IgAN as a collaborator in larger chronic glomerular disease research consortium.