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.

Public Health Relevance

Membranous histopathology is a common presentation of a group of rare diseases that cause serious morbidity and high mortality, generating enormous individual and societal economic burden. This prospective observational cohort study will provide a readily accessible resource that will significantly advance our ability to study, classify, characterize, diagnose, and treat non-inflammatory glomerular diseases

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRG1-HOP-Y)
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University of Michigan Ann Arbor
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