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

局灶节段性肾小球硬化症（FSGS）和微小病变病（MCD）是一组导致严重发病率和高死亡率的罕见疾病。人们越来越一致认为，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理解，并且因为它不能很好地预测受影响者的异质自然史或对治疗的反应。鉴于这些缺点，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的反应 干预，以便及早发现疾病，或提供疾病活动指标。重要的是，目前缺乏强大的研究基础设施来促进收集、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 FSGS/MCD 患者的护理。本申请提出了一项针对具有 FSGS/MCD 组织病理学特征的患者的协作前瞻性观察队列研究。在收集了 250 名具有这种肾活检特征的患者及其相关临床数据、肾组织、血液和尿液后，FSGS/MCD 队列研究的初步目标是：(a) 开发和使用分子表型、可量化组织学参数和离散临床特征的组合来预测临床 结果； (b)根据分子表型将患者分为离散的亚组。这些研究为临床医生带来了预测 FSGS/MCD 自然史的希望。

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.