Minimal Change Disease (MCD), Focal and Segmental Glomerulosclerosis (FSGS), Membranous Nephropathy (MN), and IgA Nephropathy (IgAN) are glomerular diseases that despite their rarity, account for a large fraction of prevalent ESKD. There is now consensus that the presently employed histopathologybased classification of these diseases 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 individuals within a given glomerular histopathological category. We propose that major barriers must be overcome before more effective interventional studies of primary chronic glomerular disease can be conducted or before patients suffering from these diseases can be properly diagnosed and treated. Among these barriers is the absence of well characterized specific biomarkers of glomerular disease that would allow refined, biologically relevant sub-classification of glomerular disease histopathology. Such disease sub-classification might overcome the effects of glomerular disease 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 would facilitate collection, cultivation, and access to human biological material and associated clinical data necessary for biomarker identification, for developing instruments useful for evaluating patient reported outcomes (PRO) that might be useful as endpoints in therapeutic trials, and for conducting pilot clinical studies that would advance the care of MCD, FSGS, MN, IgAN patients. For these reasons, we propose the establishment of PROGRESS, a Participating Clinical Center (PCC) that brings together clinical and translational scientists, a lay research foundation, and partners from the private sector to study patients with MCD, FSGS, MN and IgAN as a collaborator in larger chronic glomerular disease research consortium.
MCD, FSGS, MN, amd IgAN are rare diseases that cause serious morbidity and high mortality, generating enormous individual and societal economic burden. PROGRESS assembles nephrologists, scientists, privated entities and a lay foundation to participate in a consortium that will significantly advance our ability to study, classify, characterize, diagnose, and treat primary chronic glomerular diseases of the kidney.
|Pullen, Nick; Fornoni, Alessia (2016) Drug discovery in focal and segmental glomerulosclerosis. Kidney Int 89:1211-20|
|Wahl, Patricia; Ducasa, Gloria Michelle; Fornoni, Alessia (2016) Systemic and renal lipids in kidney disease development and progression. Am J Physiol Renal Physiol 310:F433-45|
|Pedigo, Christopher E; Ducasa, Gloria Michelle; Leclercq, Farah et al. (2016) Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury. J Clin Invest 126:3336-50|
|de Boer, Ian H; Afkarian, Maryam; Tuttle, Katherine R (2016) The Surging Tide of Diabetes: Implications for Nephrology. Am J Kidney Dis 67:364-6|
|Navaneethan, Sankar D; Boulware, L Ebony; Sedor, John R (2015) Patients as stakeholders in setting kidney disease research priorities. Am J Kidney Dis 65:641-3|
|O'Toole, John F; Sedor, John R (2014) Kidney disease: new technologies translate mechanisms to cure. J Clin Invest 124:2294-8|