Focal and Segmental Glomerulosclerosis (FSGS) & Minimal Change Disease (MCD) Coho

局灶节段性肾小球硬化(FSGS)和微小病变病(MCD)是一组发病率高、病死率高的罕见疾病。越来越多的人一致认为，目前采用的基于组织病理学的FSGS/MCD分类是有限的，因为它不是基于对这些疾病的分子基础的了解，也因为它不能很好地预测受影响者的异质性自然病史或治疗反应。考虑到这些缺点，我们对这些疾病的治疗方法不完美也就不足为奇了。我们认为，在对原发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定生物标记物，这些标记物允许对肾小球疾病组织病理学进行精细的、生物相关的子分类，有助于在临床研究中定义受试者纳入和排除标准。这种疾病分类可能会克服研究人群的异质性的影响，这种异质性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也可能预测疾病的自然病程，允许适当地选择和预测对特定治疗的反应 干预，允许及早发现疾病，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来促进人类生物材料的收集、培养和访问，以及生物标记物鉴定、临床相关研究终点的确定和开展试点临床研究以促进对FSGS/MCD患者的护理所需的相关临床数据的获取。这项应用提出了一项针对具有FSGS/MCD组织病理学特征的患者的协作性前瞻性观察队列研究。在收集了250名具有这种肾脏活检特征的患者及其相关的临床数据、肾组织、血液和尿液后，FSGS/MCD队列研究的最初目标是：(A)开发和使用分子表型、可量化的组织学参数和离散的临床特征来预测临床 结果；以及(B)根据患者的分子表型将他们分成不同的亚组。这些研究为临床医生提供了预测FSGS/MCD自然病史的希望。

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are a group of rare diseases that cause serious morbidity and high mortality. There is growing consensus that the presently employed histopathology-based classification of FSGS/MCD is limited 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 those affected. Given these shortcomings, 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 FSGS/MCD patients. This application proposes a collaborative prospective observational cohort study of patients who present with histopathology characteristic of FSGS/MCD. After collecting 250 patients with this kidney biopsy characteristic, and their associated clinical data, kidney tissue, blood, and urine, the initial goals of the FSGS/MCD Cohort study are: (a) to develop and use a combination of molecular phenotypes, quantifiable histological parameters, and discrete clinical features to predict clinical outcomes; and (b) to classify patients according to their molecular phenotype into discrete subgroups. These studies hold out the promise to the clinician of being able to predict the natural history of FSGS/MCD.