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Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

Open (Enrolling)
Minimal Change Disease (MCD), Membranous Nephropathy, Glomerulosclerosis, Focal Segmental

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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.

Inclusion Criteria:

Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric
participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting
the following inclusion criteria:

- Documented urinary protein excretion ≥500 mg/24 hours or spot protein: creatinine
ratio equivalent at the time of diagnosis or within 3 months of the
screening/eligibility visit.

- Scheduled renal biopsy

Exclusion Criteria:

- Prior solid organ transplant

- A clinical diagnosis of glomerulopathy without diagnostic renal biopsy

- Clinical, serological or histological evidence of systemic lupus erythematosus (SLE)
as defined by the ARA criteria. Patients with membranous in combination with SLE will
be excluded because this entity is well defined within the International Society of
Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently
overlaps with other classification categories of SLE nephritis (68)

- Clinical or histological evidence of other renal diseases (Alport, Nail Patella,
Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas),
genito-urinary malformations with vesico-urethral reflux or renal dysplasia)

- Known systemic disease diagnosis at time of enrollment with a life expectancy less
than 6 months

- Unwillingness or inability to give a comprehensive informed consent

- Unwillingness to comply with study procedures and visit schedule

- Institutionalized individuals (e.g., prisoners)

Type of Study:


Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

Event rate of change in urinary protein excretion and renal function.

Outcome Description:

Defined as remission, partial remission and non-remission

Outcome Time Frame:

60 months

Safety Issue:


Principal Investigator

Matthias Kretzler, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan


Canada: Ethics Review Committee

Study ID:




Start Date:

April 2010

Completion Date:

June 2014

Related Keywords:

  • Minimal Change Disease (MCD)
  • Membranous Nephropathy
  • Glomerulosclerosis, Focal Segmental
  • Focal and Segmental Glomerulosclerosis
  • Focal & Segmental Glomerulosclerosis
  • Focal Segmental Glomerulosclerosis
  • FSGS
  • Minimal change disease
  • MCD
  • Membranous Nephropathy
  • MN
  • Nephrotic Syndrome
  • Neph Syndrome
  • NephCure
  • Halpin
  • Glomerulonephritis, Membranous
  • Glomerulosclerosis, Focal Segmental
  • Kidney Diseases
  • Nephrosis, Lipoid
  • Nephrotic Syndrome



Mayo ClinicRochester, Minnesota  55905
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Montefiore Medical CenterBronx, New York  10467-2490
Stanford University School of MedicineStanford, California  94305-5317
University of WashingtonSeattle, Washington  98195
Temple UniversityPhiladelphia, Pennsylvania  19140
University of PennsylvaniaPhiladelphia, Pennsylvania  19104
University of Michigan Medical CenterAnn Arbor, Michigan  48104-0914
New York University Medical CenterNew York, New York  10016
Cleveland ClinicCleveland, Ohio  44195
Johns Hopkins Medical InstituteBaltimore, Maryland  21231
Seattle Children's HospitalSeattle, Washington  98105
Columbia University Medical CenterNew York, New York  10032
University of North Carolina at Chapel HillChapel Hill, North Carolina  27599
University Of Miami Miller School Of MedicineMiami, Florida  33010
University of Illinois - ChicagoChicago, Illinois  60612
Bellevue HospitalNew York, New York  10016
Cohen Children's HospitalNew Hyde Park, New York  11040
University of Southern California-Children's HospitalLos Angeles, California  90227
Los Angeles Biomedical Research Institute at Harbor UCLA Medical CenterTorrance, California  90502
Emory University and Children's Healthcare of AtlantaAtlanta, Georgia  30322
Kidney Disease Section, NIDDK, NIHBethesda, Maryland  20892
CS Mott Children's Hospital, University of MichiganAnn Arbor, Michigan  48109
New York University Veterans AdministrationNew York, New York  10016
MetroHealth Hospital at Case Western Medical CenterCleveland, Ohio  44109
University Hospital Rainbow Babies & Children's HospitalCleveland, Ohio  44106
Drexel UniversityPhiladelphia, Pennsylvania  19104
Providence Medical Research CenterSpokane, Washington  99204
University of Texas-SouthwesternDallas, Texas  75390