Minimal Change Disease (MCD), Focal and Segmental Glomerulosclerosis (FSGS), and Membranous Nephropathy (MN) are glomerular diseases that despite their rarity, account for a large fraction of prevalent ESRD. There is growing consensus that the presently employed histopathology-based classification of FSGS and 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 individuals within a given glomerular histopathological category. Given these inadequacies, 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 MCD, FSGS, and MN patients. For these reasons, we propose the establishment of a Nephrotic Syndrome RDCRN, a multidisciplinary research and education platform that brings together clinical and translational scientists and two lay research and patient education foundations, aimed at beginning to better study and educate patients with FSGS, MN, and MCD.

Public Health Relevance

MCD, FSGS, and MN are rare diseases that cause serious morbidity and high mortality, generating enormous individual and societal economic burden. Creation of the Nephrotic Syndrome Rare Disease Consortium will provide a readily accessible research and education 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)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-Y (50))
Program Officer
Moxey-Mims, Marva M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code
Crawford, Brendan D; Gillies, Christopher E; Robertson, Catherine C et al. (2017) Evaluating Mendelian nephrotic syndrome genes for evidence for risk alleles or oligogenicity that explain heritability. Pediatr Nephrol 32:467-476
Suleiman, Hani Y; Roth, Robyn; Jain, Sanjay et al. (2017) Injury-induced actin cytoskeleton reorganization in podocytes revealed by super-resolution microscopy. JCI Insight 2:
Beanlands, Heather; Maione, Maria; Poulton, Caroline et al. (2017) Learning to live with nephrotic syndrome: experiences of adult patients and parents of children with nephrotic syndrome. Nephrol Dial Transplant 32:i98-i105
Mariani, Laura H; Martini, Sebastian; Barisoni, Laura et al. (2017) Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies. Nephrol Dial Transplant :
Sharma, Ruchika; Waller, Amanda P; Agrawal, Shipra et al. (2017) Thrombin-Induced Podocyte Injury Is Protease-Activated Receptor Dependent. J Am Soc Nephrol 28:2618-2630
Ng, Derek K; Robertson, Catherine C; Woroniecki, Robert P et al. (2017) APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts. Nephrol Dial Transplant 32:983-990
Kikuchi, Masao; Wickman, Larysa; Rabah, Raja et al. (2017) Podocyte number and density changes during early human life. Pediatr Nephrol 32:823-834
Kim, Yeawon; Park, Sun-Ji; Chen, Ying Maggie (2017) Mesencephalic astrocyte-derived neurotrophic factor (MANF), a new player in endoplasmic reticulum diseases: structure, biology, and therapeutic roles. Transl Res 188:1-9
Kim, Yeawon; Park, Sun-Ji; Manson, Scott R et al. (2017) Elevated urinary CRELD2 is associated with endoplasmic reticulum stress-mediated kidney disease. JCI Insight 2:
Hladunewich, Michelle A; Beanlands, Heather; Herreshoff, Emily et al. (2017) Provider perspectives on treatment decision-making in nephrotic syndrome. Nephrol Dial Transplant 32:i106-i114

Showing the most recent 10 out of 63 publications