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

局灶性和节段性肾小球硬化症 (FSGS)

• 批准号: 8328116
• 负责人: DANIEL C. CATTRAN
• 金额: $ 25.79万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8328116
• 关键词: Affect; Area; Biological Markers; Biopsy; Blood; Caring; Characteristics; Classification; Clinical; Clinical Data; Clinical Research; Clinical Trials; Cohort Studies; Collection; Commit; Consensus; Diagnosis; Disease; Disease remission; Early Diagnosis; Economic Burden; Education; End stage renal failure; Event; Exclusion Criteria; Excretory function; Focal Segmental Glomerulosclerosis; Foundations; Frequencies; Future; Gene Expression; Genetic; Goals; Heterogeneity; Histopathology; Individual; Investigation; Kidney; Knowledge; Maps; Molecular; Molecular Profiling; Morbidity - disease rate; Mutation; Natural History; Nephrotic Syndrome; Outcome; Pathway interactions; Patients; Population Heterogeneity; Process; Proteins; Rare Diseases; Renal Tissue; Renal function; Renal glomerular disease; Research; Research Infrastructure; Research Personnel; Resources; Specific qualifier value; Subgroup; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Urine; WT1 gene; base; clinically relevant; cohort; disease natural history; follow-up; genome-wide; hazard; human biological material; inclusion criteria; insight; molecular phenotype; mortality; new therapeutic target; prospective; research study; response; therapeutic target; treatment duration; urinary

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.

局灶节段性肾小球硬化症（FSGS）和微小病变病（MCD）是一组发病率高、死亡率高的罕见病。越来越多的共识认为，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，因为它不能很好地预测异质性的自然史或对受影响的治疗的反应。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，在对原发性非炎症性肾小球疾病进行更有效的干预性研究之前，必须克服几个主要障碍。在这些障碍中，缺乏肾小球疾病的特异性生物标志物，其将允许肾小球疾病组织病理学的精细的、生物学相关的亚分类，其可用于定义临床研究中的受试者入选和排除标准。这样的疾病亚分类可能克服研究人群异质性的影响，这些异质性可能使这些肾小球疾病的过去研究的解释复杂化。新的肾小球疾病生物标志物也可能预测疾病的自然史，允许适当选择和预测对特定治疗的反应。 干预，允许早期发现疾病或提供疾病活动的指标。重要的是，目前缺乏一个强大的研究基础设施，这将有助于收集、培养和获得生物标志物鉴定所需的人体生物材料和相关临床数据，以确定临床相关研究终点，并进行试点临床研究，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性队列研究。在收集了250例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临床特征的组合来预测临床特征， 结果;和（B）根据患者的分子表型将其分类为离散的亚组。这些研究为临床医生预测FSGS/MCD的自然病程提供了希望。