Membranous Nephropathy Observational Cohort Study

膜性肾病观察队列研究

• 批准号: 8538363
• 负责人: FERNANDO C FERVENZA
• 金额: $ 98.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2014-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8538363
• 关键词: Accounting; Address; Affect; Area; Basic Science; Biological; Biological Markers; Biology; Biopsy; Blood; Caring; Categories; Characteristics; Classification; Clinical; Clinical Data; Clinical Research; Cohort Studies; Collection; Consensus; County; Databases; Diagnosis; Disease; Early Diagnosis; Economic Burden; End stage renal failure; Exclusion Criteria; Focal Segmental Glomerulosclerosis; Goals; Heterogeneity; Histology; Histopathology; Hypertension; Idiopathic Membranous Nephropathy; Incidence; Individual; Information Systems; Kidney; Kidney Diseases; Knowledge; Membranous Glomerulonephritis; Minnesota; Molecular; Morbidity - disease rate; Natural History; Nephrotic Syndrome; Outcome; Patient Care; Patients; Population; Population Heterogeneity; Prevalence; Process; Rare Diseases; Recruitment Activity; Renal glomerular disease; Reporting; Research Design; Research Infrastructure; Resources; Subgroup; System; Therapeutic; Therapeutic Intervention; Tissues; Toxic effect; United States; Urine; base; clinically relevant; cost; cost effective; disease natural history; human biological material; inclusion criteria; molecular phenotype; mortality; population based; programs; prospective; research study; response

Idiopathic Membranous Nephropathy (MN) is a group of rare diseases that results in often catastrophic complications of nephrotic syndrome and end stage kidney disease. There is growing consensus that the presently employed histopathology-based classification of 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 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 addressed to allow for more effective interventional studies of primary non-inflammatory glomerular disease. Among these barriers is the absence of specific biomarkers of glomerular disease that would allow refined, biologically relevant sub-classification of glomerular disease 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 MN patients. This application proposes a collaborative prospective observational cohort study of patients who present with histopathology characteristic of membranous glomerulopathy. After collecting 200 patients with this kidney biopsy characteristic, and their associated clinical data, kidney tissue, blood, and urine, the initial goals of the MN 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. Given the paucity of knowledge in this area, these initial experiments are meant as hypothesis generating. Additional confirmatory studies will be required to validate initial observations. These studies hold out the promise to the clinician of being able to predict the natural history of MN.

特发性膜性肾病 (MN) 是一组罕见疾病，通常会导致灾难性的后果 肾病综合征和终末期肾病的并发症。人们越来越一致认为 目前采用的基于组织病理学的 MN 分类是不够的，因为它不是基于 了解这些疾病的分子基础，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。考虑到这些缺点，不 令人惊讶的是，我们对这些疾病的治疗方法并不完美。我们建议几个主要 必须解决障碍，以便对原发性非炎症性疾病进行更有效的介入研究 肾小球疾病。这些障碍之一是缺乏肾小球疾病的特异性生物标志物， 将允许对肾小球疾病进行精细的、生物学相关的子分类，有助于定义受试者 临床研究中的纳入和排除标准。这种疾病细分可能会克服 研究群体异质性的影响可能会使对这些研究的过去研究的解释变得复杂 肾小球疾病。新的肾小球疾病生物标志物也可能预测疾病自然史，允许 正确选择和预测对特定治疗干预的反应，可以及早发现 疾病，或提供疾病活动的指标。重要的是，目前已建立健全的调查基础设施 如果缺乏这一点，将有利于人类生物材料和相关材料的收集、培养和获取 生物标志物鉴定所需的临床数据，用于鉴定临床相关研究终点， 并进行试点临床研究，以促进 MN 患者的护理。这个应用程序 提出了一项针对出现组织病理学表现的患者的协作前瞻性观察队列研究 膜性肾小球病的特征。在收集了 200 名患者的肾活检样本后 特征及其相关临床数据、肾组织、血液和尿液，MN 的初始目标 队列研究是：（a）开发和使用分子表型、可量化组织学的组合 参数和离散临床特征来预测临床结果； (b) 对患者进行分类 将它们的分子表型分为离散的亚组。鉴于该领域知识的匮乏，这些 初始实验旨在生成假设。需要进行额外的验证性研究 验证初步观察结果。这些研究为临床医生带来了能够预测病情的希望 MN 的自然史。