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Nefrotisk syndrom undersøgelsesnetværk (NEPTUNE)

5. november 2026 opdateret af: Matthias Kretzler, University of Michigan

Nefrotisk syndrom undersøgelsesnetværk under det kliniske forskningsnetværk for sjældne sygdomme

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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Observationel

Tilmelding (Anslået)

1200

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

Studiesteder

  • Canada
    • Ontario
      • Richmond Hill, Ontario, Canada, L4C 4Z3
        • Afsluttet
        • York Central Hospital
      • Scarborough Village, Ontario, Canada, M1H 3G4
        • Afsluttet
        • Scarborough Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Rekruttering
        • Sunnybrook Hospital
        • Ledende efterforsker:
          • Michelle Hladunewich, MD
        • Kontakt:
      • Toronto, Ontario, Canada, L5M 2N1
        • Rekruttering
        • Credit Valley Hospital
        • Underforsker:
          • Phillip Boll, MD
        • Kontakt:
      • Toronto, Ontario, Canada, M5G2C4
        • Rekruttering
        • University Health Network
        • Kontakt:
        • Kontakt:
        • Ledende efterforsker:
          • Daniel Cattran, MD
        • Underforsker:
          • Heather Reich, MD
        • Underforsker:
          • Michelle Hladunewich, MD
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90227
        • Rekruttering
        • University of Southern California-Children's Hospital
        • Ledende efterforsker:
          • Kevin Lemley, MD, PhD
        • Kontakt:
      • Palo Alto, California, Forenede Stater, 94304
        • Rekruttering
        • Stanford University School of Medicine
        • Kontakt:
        • Ledende efterforsker:
          • Richard Lafayette, MD
      • San Francisco, California, Forenede Stater, 94158
        • Ikke rekrutterer endnu
        • University of California San Francisco Benioff Children's Hospitals
        • Ledende efterforsker:
          • Paul Brakeman, MD, PhD
        • Kontakt:
      • Torrance, California, Forenede Stater, 90502
        • Rekruttering
        • Lundquist Biomedical Research Institute at Harbor UCLA Medical Center
        • Kontakt:
        • Ledende efterforsker:
          • Sharon Adler, MD
    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
      • Aurora, Colorado, Forenede Stater, 80045
        • Ikke rekrutterer endnu
        • University of Colorado Anschutz School of Medicine
        • Ledende efterforsker:
          • Amber Podoll, MD
        • Kontakt:
    • Florida
      • Miami, Florida, Forenede Stater, 33136
        • Rekruttering
        • University of Miami Miller School of Medicine
        • Kontakt:
        • Ledende efterforsker:
          • Alessia Fornoni, MD. PhD
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30322
        • Rekruttering
        • Emory University and Children's Healthcare of Atlanta
        • Ledende efterforsker:
          • Laurence Greenbaum, MD, PhD
        • Kontakt:
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60680
        • Rekruttering
        • John Stroger Cook County Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Ambarish Athavale, MD
    • Kansas
      • Kansas City, Kansas, Forenede Stater, 66160
        • Rekruttering
        • University of Kansas Medical Center
        • Kontakt:
        • Ledende efterforsker:
          • Ellen McCarthy, MD
    • Maryland
      • Baltimore, Maryland, Forenede Stater, 21287
        • Rekruttering
        • Johns Hopkins Medical Institute
        • Kontakt:
        • Ledende efterforsker:
          • Alicia Neu, MD
        • Underforsker:
          • Michael Choi, MD
      • Bethesda, Maryland, Forenede Stater, 20892
        • Afsluttet
        • Kidney Disease Section, NIDDK, NIH
    • Michigan
      • Ann Arbor, Michigan, Forenede Stater, 48109
        • Rekruttering
        • University of Michigan Medical Center
        • Kontakt:
        • Ledende efterforsker:
          • Matthias Kretzler, MD
        • Kontakt:
          • Amanda Williams, BS - adult
          • Telefonnummer: 734-615-5017
          • E-mail: amwi@umich.edu
      • Ann Arbor, Michigan, Forenede Stater, 48109
        • Rekruttering
        • CS Mott Children's Hospital, University of Michigan
        • Underforsker:
          • Debbie Gipson, MD, MS
        • Kontakt:
    • Minnesota
      • Rochester, Minnesota, Forenede Stater, 55905
        • Afsluttet
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, Forenede Stater, 64108
        • Rekruttering
        • Children's Mercy Hospital
        • Ledende efterforsker:
          • Tarak Srivastava, MD
        • Kontakt:
      • St Louis, Missouri, Forenede Stater, 63110
        • Ikke rekrutterer endnu
        • Washington University - St Louis
        • Kontakt:
        • Ledende efterforsker:
          • Vikas Dharnidharka, MD, PhD
    • New York
      • New Hyde Park, New York, Forenede Stater, 11040
        • Rekruttering
        • Cohen Children's Hospital
        • Ledende efterforsker:
          • Christine Sethna, MD
        • Kontakt:
      • New York, New York, Forenede Stater, 10032
        • Rekruttering
        • Columbia University Medical Center
        • Ledende efterforsker:
          • Andrew Bomback, MD, MPH
        • Kontakt:
      • New York, New York, Forenede Stater, 10010
        • Rekruttering
        • New York University Medical Center
        • Kontakt:
        • Ledende efterforsker:
          • Olga Zhadnova, MD
        • Ledende efterforsker:
          • Howard Trachtman, MD
        • Kontakt:
      • New York, New York, Forenede Stater, 10016
        • Rekruttering
        • Bellevue Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Laura Barisoni, MD
        • Underforsker:
          • Olga Zhadnova, MD
      • New York, New York, Forenede Stater, 10016
        • Rekruttering
        • New York University Veterans Administration
        • Kontakt:
        • Ledende efterforsker:
          • Laura Barisoni, MD
        • Underforsker:
          • Olga Zhadnova, MD
      • The Bronx, New York, Forenede Stater, 11040
        • Rekruttering
        • Montefiore Medical Center
        • Kontakt:
        • Underforsker:
          • Robert Woroniecki, MD
        • Ledende efterforsker:
          • Frederick Kaskel, MD
    • North Carolina
      • Chapel Hill, North Carolina, Forenede Stater, 27599
        • Rekruttering
        • University of North Carolina at Chapel Hill
        • Kontakt:
        • Ledende efterforsker:
          • Patrick H. Nachman, MD
        • Underforsker:
          • Susan L. Hogan, PhD, MPH
        • Underforsker:
          • Keisha Gibson, MD
        • Kontakt:
      • Charlotte, North Carolina, Forenede Stater, 28203
        • Rekruttering
        • Atrium Health Levine Children's Hospital
        • Ledende efterforsker:
          • Susan Massengill, MD
        • Kontakt:
      • Winston-Salem, North Carolina, Forenede Stater, 27157
        • Trukket tilbage
        • Wake Forest School of Medicine
    • Ohio
      • Cleveland, Ohio, Forenede Stater, 44195
        • Rekruttering
        • Cleveland Clinic
        • Underforsker:
          • Katherine Dell, MD
        • Kontakt:
        • Kontakt:
          • Villarreal
      • Cleveland, Ohio, Forenede Stater, 44106
        • Afsluttet
        • University Hospital Rainbow Babies & Children's Hospital
      • Cleveland, Ohio, Forenede Stater, 44109
        • Afsluttet
        • MetroHealth Hospital at Case Western Medical Center
      • Columbus, Ohio, Forenede Stater, 43210
        • Rekruttering
        • The Ohio State University Wexner Medical Center
        • Kontakt:
        • Ledende efterforsker:
          • Salem Almaani, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
        • Rekruttering
        • University of Pennsylvania
        • Kontakt:
        • Ledende efterforsker:
          • Lawrence Holzman, MD
        • Kontakt:
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
        • Rekruttering
        • Children's Hospital of Philadelphia
        • Underforsker:
          • Kevin Meyers, MD
        • Kontakt:
      • Philadelphia, Pennsylvania, Forenede Stater, 19140
        • Rekruttering
        • Temple University
        • Kontakt:
        • Ledende efterforsker:
          • Crystal Gadegbeku, MD
        • Ledende efterforsker:
          • Iris Lee, MD
    • South Carolina
      • Charleston, South Carolina, Forenede Stater, 29425
        • Rekruttering
        • Medical University of South Carolina
        • Ledende efterforsker:
          • David Selewski, MD, MS
    • Texas
      • Dallas, Texas, Forenede Stater, 75390
      • Houston, Texas, Forenede Stater, 77030
        • Rekruttering
        • Texas Children's Hospital - Baylor College of Medicine
        • Kontakt:
        • Ledende efterforsker:
          • Shweta S. Shah, MD
    • Washington
      • Seattle, Washington, Forenede Stater, 98195
      • Seattle, Washington, Forenede Stater, 98145
      • Spokane, Washington, Forenede Stater, 99204

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

Ikke ældre end 80 år (Barn, Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

Patients with signs and symptoms of kidney disease consistent with FSGS, MCD, MN or proteinuric renal disease or pediatric participants not previously biopsied, who present for patient care at participating clinical centers will be eligible for Cohort A (biopsy cohort) study population targeted for enrollment into the NEPTUNE study.

To establish a cohort of pediatric participants with incident nephrotic syndrome, Cohort B, a non-biopsy cohort has been initiated for Protocol V4.0. This population, <19 years of age, presenting for nephrotic syndrome and less than 30 days of immunosuppression therapy exposure, will also be targeted for enrollment into the cNEPTUNE study.

Potential participants willing to receive their initial care and subsequent follow-up study visits at one of these sites are welcome to participate.

Beskrivelse

Cohort A (biopsy cohort) 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 ≥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

Cohort B (non-biopsy, cNEPTUNE) Inclusion Criteria:

  • 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 (Cohort A&B):

  • 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)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Observationsmodeller: COHORT
  • Tidsperspektiver: PROSPECTIVE

Kohorter og interventioner

Gruppe / kohorte
Intervention / Behandling
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.
Procedure: 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.
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.
Procedure: 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.
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.
Procedure: 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.
cNEPTUNE (Cohort B)

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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Event rate of change in urinary protein excretion and renal function.
Tidsramme: 60 months

Defined as remission, partial remission and non-remission
60 months
Rate of change in renal function.
Tidsramme: 60 months

Defined as:

  1. 25 mls/min/1.73m2 reduction in follow-up estimated GFR (using the 4-variable MDRD equation for ages ≥18 years and modified Schwartz for ages <18 years) compared to baseline estimated GFR
  2. 50% decline in follow-up estimated GFR compared to baseline measurement
  3. End stage renal disease defined as estimated GFR ≤10cc/min, initiation of maintenance dialysis or preemptive kidney transplantation.
60 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Quality of Life:
Tidsramme: 60 months

Patient-reported outcome will be assessed using Quality of Life questionnaires at regular intervals as stipulated in the visit calendar using the SF-36, PedsQL and the Patient Reported Outcome Measurement Information System (PROMIS) (in the age-appropriate groups).
60 months
Malignancies
Tidsramme: 60 months

Any cancer diagnosis of the skin, hematopoietic system, or solid organ after enrollment in NEPTUNE
60 months
Infections, Serious and Systemic
Tidsramme: 60 months

Infections including one of the following:

  1. Documented diagnosis of infection of the skin or subcutaneous tissue (e.g. cellulitis), vascular system, peritoneum, or any vital organ requiring the use of parenteral antibiotics and/or oral antibiotics alone or in combination for a treatment interval of ≥72 hours.
  2. Hospitalization for treatment of infection
60 months
Thromboembolic Events
Tidsramme: 60 months

Documented diagnosis of one of the following:

  1. Embolic cerebrovascular accident
  2. Deep venous thrombosis
  3. Renal vein thrombosis or
  4. Pulmonary embolus
60 months
Hospitalization
Tidsramme: 60 months

Documented hospital admission, including observation for ≥24 hours.
60 months
Emergency Department/ Observation Unit Visit
Tidsramme: 60 months

Documented visit to an emergency department or observation unit that does not lead to hospitalization and is less than 24 hours.
60 months
Acute Kidney Injury
Tidsramme: 60 months

Documented diagnosis of acute kidney injury as defined by the AKIN (Mehta et al., Critical Care 2007, 11:R31) and/or renal failure requiring renal replacement therapy <3 months.
60 months
Death
Tidsramme: 60 months
  1. Documentation of death that is secondary to infection or sepsis.
  2. Cardiovascular/Cerebrovascular-related Death: Sudden death; Myocardial infarction; Congestive heart failure; Primary intractable serious arrhythmia; Peripheral vascular disease; Ischemic cerebrovascular accident; Hemorrhagic cerebrovascular accident; Thromboembolic event
  3. Documentation of death secondary to cancer
  4. Other Death: Documentation of death that does not fall into the above categories.
60 months
New Onset Diabetes
Tidsramme: 60 months

Diagnosis of diabetes as indicated by 1 or more of the following not present at NEPTUNE Enrollment:

  1. Documented diagnosis of diabetes in medical record
  2. Casual (non-fasting) blood glucose > 200 mg/dL c) Fasting blood glucose > 126 mg/dL d) 2 hour glucose > 200 after oral glucose tolerance test e) chronic use (>6 mos) hypoglycemic therapy outside of pregnancy f) Hemogloblin A1C >= 6.5%
60 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Michigan

Samarbejdspartnere

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
The NephCure Foundation

Efterforskere

  • Ledende efterforsker: Matthias Kretzler, MD, University of Michigan

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. april 2010

Primær færdiggørelse (Anslået)

31. december 2030

Studieafslutning (Anslået)

31. december 2030

Datoer for studieregistrering

Først indsendt

29. juli 2010

Først indsendt, der opfyldte QC-kriterier

23. september 2010

Først opslået (Anslået)

24. september 2010

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

10. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

5. november 2026

Sidst verificeret

1. november 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 6801
  • 1U54DK083912 (U.S. NIH-bevilling/kontrakt)
  • 1R01DK141114-01A1 (U.S. NIH-bevilling/kontrakt)

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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