Nephrotic Syndrome Study Network

NCT ID: NCT01209000

Last Updated: 2025-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-04-30

Study Completion Date

2029-06-30

Brief Summary

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Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and Membranous nephropathy (MN), generate an enormous individual and societal financial burden, accounting for approximately 12% of prevalent end stage renal disease (ESRD) cases (2005) at an annual cost in the US of more than $3 billion. However, the clinical classification of these diseases is widely believed to be inadequate by the scientific community. Given the poor understanding of MCD/FSGS and MN biology, it is not surprising that the available therapies are imperfect. The therapies lack a clear biological basis, and as many families have experienced, they are often not beneficial, and in fact may be significantly toxic. Given these observations, it is essential that research be conducted that address these serious obstacles to effectively caring for patients.

In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium.

Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.

Detailed Description

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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.

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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FSGS/MCD Cohort (Cohort A)

Focal Segmental Glomerulosclerosis/Minimal Change Disease (FSGS/MCD) Cohort

Participants enrolled in NEPTUNE with a biopsy proven histological diagnosis for FSGS or MCD.

Eligible participants must be scheduled for a clinically indicated renal biopsy.

Kidney Biopsy

Intervention Type PROCEDURE

Patients scheduled to undergo a clinically indicated kidney biopsy will be requested to consent to an additional renal core, to be set aside until all clinical care is complete.

MN Cohort (Cohort A)

Membranous Nephropathy (MN) Cohort

Participants enrolled in NEPTUNE with a biopsy proven histological diagnosis for MN.

Eligible participants must be scheduled for a clinically indicated renal biopsy.

Kidney Biopsy

Intervention Type PROCEDURE

Patients scheduled to undergo a clinically indicated kidney biopsy will be requested to consent to an additional renal core, to be set aside until all clinical care is complete.

Other glomerulopathies cohort

Participants enrolled in NEPTUNE and determined to not have FSGS/MCD or MN will be followed in a third group.

Eligible participants must be scheduled for a clinically indicated renal biopsy.

Kidney Biopsy

Intervention Type PROCEDURE

Patients scheduled to undergo a clinically indicated kidney biopsy will be requested to consent to an additional renal core, to be set aside until all clinical care is complete.

cNEPTUNE (Cohort B)

Participants \< 19 years of age, with \< 30 days exposure to immunosuppression therapy who are not scheduled for renal biopsy.

No interventions assigned to this group

Interventions

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Kidney Biopsy

Patients scheduled to undergo a clinically indicated kidney biopsy will be requested to consent to an additional renal core, to be set aside until all clinical care is complete.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Documented urinary protein excretion ≥1500 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


* Age \<19 years of age
* Initial presentation with \<30 days immunosuppression therapy
* Proteinuria/nephrotic

* UA\>2+ and edema OR
* UA\>2+ and serum albumin \<3 OR
* UPC \> 2g/g and serum albumin \<3

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)
Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

The NephCure Foundation

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role lead

Responsible Party

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Matthias Kretzler

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Matthias Kretzler, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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University of Southern California-Children's Hospital

Los Angeles, California, United States

Site Status RECRUITING

Stanford University School of Medicine

Palo Alto, California, United States

Site Status RECRUITING

University of California San Francisco Benioff Children's Hospitals

San Francisco, California, United States

Site Status NOT_YET_RECRUITING

Lundquist Biomedical Research Institute at Harbor UCLA Medical Center

Torrance, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status NOT_YET_RECRUITING

University of Colorado Anschutz School of Medicine

Aurora, Colorado, United States

Site Status NOT_YET_RECRUITING

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status RECRUITING

Emory University and Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status RECRUITING

John Stroger Cook County Hospital

Chicago, Illinois, United States

Site Status RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

Johns Hopkins Medical Institute

Baltimore, Maryland, United States

Site Status RECRUITING

Kidney Disease Section, NIDDK, NIH

Bethesda, Maryland, United States

Site Status COMPLETED

CS Mott Children's Hospital, University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status COMPLETED

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status RECRUITING

Washington University - St Louis

St Louis, Missouri, United States

Site Status NOT_YET_RECRUITING

Cohen Children's Hospital

New Hyde Park, New York, United States

Site Status RECRUITING

New York University Medical Center

New York, New York, United States

Site Status RECRUITING

Bellevue Hospital

New York, New York, United States

Site Status RECRUITING

New York University Veterans Administration

New York, New York, United States

Site Status RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Atrium Health Levine Children's Hospital

Charlotte, North Carolina, United States

Site Status RECRUITING

Wake Forest School of Medicine

Winston-Salem, North Carolina, United States

Site Status WITHDRAWN

University Hospital Rainbow Babies & Children's Hospital

Cleveland, Ohio, United States

Site Status COMPLETED

MetroHealth Hospital at Case Western Medical Center

Cleveland, Ohio, United States

Site Status COMPLETED

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Temple University

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status RECRUITING

University of Texas-Southwestern

Dallas, Texas, United States

Site Status RECRUITING

Texas Children's Hospital - Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Providence Medical Research Center

Spokane, Washington, United States

Site Status RECRUITING

York Central Hospital

Richmond Hill, Ontario, Canada

Site Status COMPLETED

Scarborough Hospital

Scarborough Village, Ontario, Canada

Site Status COMPLETED

Credit Valley Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Sunnybrook Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Chrysta C. Lienczewski, BS

Role: CONTACT

734-615-5021

Amanda Williams, BS

Role: CONTACT

734-615-5017

Facility Contacts

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Sharon Tang, BSN

Role: primary

323-361-7299

Kshama Mehta, PhD

Role: primary

650-736-1822

Daniel Schrader

Role: primary

Janine LaPage

Role: primary

310-222-4104

Nathan Rogers

Role: primary

Elizabeth Wagner

Role: primary

Carlos Bidot

Role: primary

305-243-8973

Emily Yun

Role: primary

404-712-9998

Mathew Itteera

Role: primary

312-864-4614

Catherine Creed

Role: primary

Sara Boynton

Role: primary

443-287-9051

Hailey Desmond, MS

Role: primary

734-232-4851

Chrysta C. Lienczewski, BS - adult

Role: primary

734-615-5021

Amanda Williams, BS - adult

Role: backup

734-615-5017

Kelsey Markus

Role: primary

Leslie Walther

Role: primary

Suzanne Vento, BSN

Role: primary

718-470-3499

Frank Modersitzki, MPH - adult

Role: primary

212-686-7500 ext. 6379

Laura Jane Pehrson - peds

Role: backup

Frank Modersitzki, MPH

Role: primary

212-686-7500 ext. 6379

Frank Modersitzki, MPH

Role: primary

212-686-7500 ext. 6379

Anup Pradhan

Role: primary

212-305-6842

Patti Flynn, RN

Role: primary

718-655-1120

Anne Froment

Role: primary

919-923-1382

Fernanda Ochoa

Role: backup

Layla Lo

Role: primary

Stefanie Larson

Role: primary

Villarreal

Role: backup

Alexander Price

Role: primary

Alilya Edwards

Role: primary

Krishna Kallem, MD - adult, MS

Role: primary

484-358-0315

Aliya Edwards - peds

Role: backup

Zoe Pfeffer, BS

Role: primary

215-707-4712

Elizabeth Robles

Role: primary

Aisha Deslandes

Role: primary

Emily Pao

Role: primary

Linda Manahan, BSN

Role: primary

Ann Cooper, CCRC

Role: primary

509-474-4327

Kelli Kuykendall, CCRC

Role: backup

509-474-4320

Martin Romano, MD

Role: primary

416-340-3514

Rhea O'Neill

Role: primary

Paul Ling, MD

Role: primary

416-340-3514

Martin Romano, MD

Role: backup

References

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Wang CS, Troost JP, Wang Y, Greenbaum LA, Gibson K, Trachtman H, Srivastava T, Reidy K, Kaskel F, Sethna CB, Meyers K, Dell KM, Tran CL, Hingorani S, Lemley KV, Lin JJ, Gipson DS. Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes. Pediatr Nephrol. 2022 Jul;37(7):1585-1595. doi: 10.1007/s00467-021-05176-8. Epub 2021 Nov 18.

Reference Type DERIVED
PMID: 34796395 (View on PubMed)

Solagna F, Tezze C, Lindenmeyer MT, Lu S, Wu G, Liu S, Zhao Y, Mitchell R, Meyer C, Omairi S, Kilic T, Paolini A, Ritvos O, Pasternack A, Matsakas A, Kylies D, Wiesch JSZ, Turner JE, Wanner N, Nair V, Eichinger F, Menon R, Martin IV, Klinkhammer BM, Hoxha E, Cohen CD, Tharaux PL, Boor P, Ostendorf T, Kretzler M, Sandri M, Kretz O, Puelles VG, Patel K, Huber TB. Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs. J Clin Invest. 2021 Jun 1;131(11):e135821. doi: 10.1172/JCI135821.

Reference Type DERIVED
PMID: 34060483 (View on PubMed)

Kang H, Kim DR, Jung YH, Baek CW, Park YH, In Oh J, Kim WJ, Choi GJ. Pre-warming the Streamlined Liner of the Pharynx Airway (SLIPA) improves fitting to the laryngeal structure: a randomized, double-blind study. BMC Anesthesiol. 2015 Nov 20;15:167. doi: 10.1186/s12871-015-0151-4.

Reference Type DERIVED
PMID: 26589142 (View on PubMed)

Hogan MC, Lieske JC, Lienczewski CC, Nesbitt LL, Wickman LT, Heyer CM, Harris PC, Ward CJ, Sundsbak JL, Manganelli L, Ju W, Kopp JB, Nelson PJ, Adler SG, Reich HN, Holzmann LB, Kretzler M, Bitzer M. Strategy and rationale for urine collection protocols employed in the NEPTUNE study. BMC Nephrol. 2015 Nov 17;16:190. doi: 10.1186/s12882-015-0185-3.

Reference Type DERIVED
PMID: 26577187 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://rarediseasesnetwork.org

Rare Diseases Clinical Research Networks Homepage

http://www.nephcure.org

Patient Advocacy group for FSGS/MCD

http://www.halpinfoundation.org/

Patient advocacy group for MN

http://www.neptune-study.org

The NEPTUNE Study Homepage

Other Identifiers

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1U54DK083912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

6801

Identifier Type: -

Identifier Source: org_study_id

NCT01240564

Identifier Type: -

Identifier Source: nct_alias

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