Trial Information

Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

Idiopathic Nephrotic Syndrome (NS) is a rare disease syndrome responsible for approximately
12% of all causes of end-stage kidney disease (ESRD) and up to 20% of ESRD in children.
Treatment strategies for Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change
Disease (MCD) and Membranous Nephropathy (MN), the major causes of NS, include high dose
prolonged steroid therapy, cyclophosphamide, cyclosporine A, tacrolimus, mycophenolate
mofetil and other immunosuppressive agents, which all carry significant side effects.
Failure to obtain remission using the current treatment approaches frequently results in
progression to ESRD with its associated costs, morbidities, and mortality. In the North
American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry, half of the
pediatric patients with Steroid Resistant Nephrotic Syndrome required renal replacement
therapy within two years of being enrolled in the disease registry. FSGS also has a high
recurrence rate following kidney transplantation (30-40%) and is the most common recurrent
disease leading to allograft loss.

The prevailing classification of Nephrotic Syndrome categorizes patients into FSGS, MCD, and
MN, if in the absence of other underlying causes, glomerular histology shows a specific
histological pattern. This classification does not adequately predict the heterogeneous
natural history of patients with FSGS, MCD, and MN. Major advances in understanding the
pathogenesis of FSGS and MCD have come over the last ten years from the identification of
several mutated genes responsible for causing Steroid Resistant Nephrotic Syndrome (SRNS)
presenting with FSGS or MCD histopathology in humans and model organisms. These functionally
distinct genetic disorders can present with indistinguishable FSGS lesions on histology
confirming the presence of heterogeneous pathogenic mechanisms under the current
histological diagnoses.

The limited understanding of FSGS, MCD, and MN biology in humans has necessitated a
descriptive classification system in which heterogeneous disorders are grouped together.
This invariably consigns these heterogeneous patients to the same therapeutic approaches,
which use blunt immunosuppressive drugs that lack a clear biological basis, are often not
beneficial, and are complicated by significant toxicity. The foregoing shortcomings make a
strong case that concerted and innovative investigational strategies combining basic
science, translational, and clinical methods should be employed to study FSGS, MCD, and MN.
It is for these reasons that the Nephrotic Syndrome Study Network is established to conduct
clinical and translational research in patients with FSGS/MCD and MN.