Nephrotic Syndrome Study Network (NEPTUNE)

January 3, 2024 updated by: Matthias Kretzler, University of Michigan

Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

1200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Richmond Hill, Ontario, Canada, L4C 4Z3
        • Completed
        • York Central Hospital
      • Scarborough, Ontario, Canada, M1H 3G4
        • Completed
        • Scarborough Hospital
      • Toronto, Ontario, Canada, L5M 2N1
        • Recruiting
        • Credit Valley Hospital
        • Sub-Investigator:
          • Phillip Boll, MD
        • Contact:
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Hospital
        • Principal Investigator:
          • Michelle Hladunewich, MD
        • Contact:
      • Toronto, Ontario, Canada, M5G2C4
        • Recruiting
        • University Health Network
        • Contact:
        • Contact:
        • Principal Investigator:
          • Daniel Cattran, MD
        • Sub-Investigator:
          • Heather Reich, MD
        • Sub-Investigator:
          • Michelle Hladunewich, MD
  • United States
    • California
      • Los Angeles, California, United States, 90227
        • Recruiting
        • University of Southern California-Children's Hospital
        • Principal Investigator:
          • Kevin Lemley, MD, PhD
        • Contact:
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University School of Medicine
        • Contact:
        • Principal Investigator:
          • Richard Lafayette, MD
      • San Francisco, California, United States, 94158
        • Not yet recruiting
        • University of California San Francisco Benioff Children's Hospitals
        • Contact:
        • Principal Investigator:
          • Paul Brakeman, MD, PhD
      • Torrance, California, United States, 90502
        • Recruiting
        • Lundquist Biomedical Research Institute at Harbor UCLA Medical Center
        • Contact:
        • Principal Investigator:
          • Sharon Adler, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
      • Aurora, Colorado, United States, 80045
        • Not yet recruiting
        • University of Colorado Anschutz School of Medicine
        • Principal Investigator:
          • Amber Podoll, MD
        • Contact:
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine
        • Contact:
        • Principal Investigator:
          • Alessia Fornoni, MD. PhD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University and Children's Healthcare of Atlanta
        • Principal Investigator:
          • Laurence Greenbaum, MD, PhD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60680
        • Recruiting
        • John Stroger Cook County Hospital
        • Contact:
        • Principal Investigator:
          • Ambarish Athavale, MD
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Contact:
        • Principal Investigator:
          • Ellen McCarthy, MD
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Medical Institute
        • Contact:
        • Principal Investigator:
          • Alicia Neu, MD
        • Sub-Investigator:
          • Michael Choi, MD
      • Bethesda, Maryland, United States, 20892
        • Completed
        • Kidney Disease Section, NIDDK, NIH
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Medical Center
        • Contact:
        • Principal Investigator:
          • Matthias Kretzler, MD
        • Contact:
          • Amanda Williams, BS - adult
          • Phone Number: 734-615-5017
          • Email: amwi@umich.edu
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • CS Mott Children's Hospital, University of Michigan
        • Sub-Investigator:
          • Debbie Gipson, MD, MS
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Completed
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospital
        • Principal Investigator:
          • Tarak Srivastava, MD
        • Contact:
      • Saint Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University - St Louis
        • Contact:
        • Principal Investigator:
          • Vikas Dharnidharka, MD, PhD
    • New York
      • Bronx, New York, United States, 11040
        • Recruiting
        • Montefiore Medical Center
        • Contact:
        • Sub-Investigator:
          • Robert Woroniecki, MD
        • Principal Investigator:
          • Frederick Kaskel, MD
      • New Hyde Park, New York, United States, 11040
        • Recruiting
        • Cohen Children's Hospital
        • Principal Investigator:
          • Christine Sethna, MD
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Principal Investigator:
          • Andrew Bomback, MD, MPH
        • Contact:
      • New York, New York, United States, 10010
        • Recruiting
        • New York University Medical Center
        • Contact:
        • Principal Investigator:
          • Olga Zhadnova, MD
        • Principal Investigator:
          • Howard Trachtman, MD
        • Contact:
      • New York, New York, United States, 10016
        • Recruiting
        • Bellevue Hospital
        • Contact:
        • Principal Investigator:
          • Laura Barisoni, MD
        • Sub-Investigator:
          • Olga Zhadnova, MD
      • New York, New York, United States, 10016
        • Recruiting
        • New York University Veterans Administration
        • Contact:
        • Principal Investigator:
          • Laura Barisoni, MD
        • Sub-Investigator:
          • Olga Zhadnova, MD
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina at Chapel Hill
        • Contact:
        • Principal Investigator:
          • Patrick H. Nachman, MD
        • Sub-Investigator:
          • Susan L. Hogan, PhD, MPH
        • Sub-Investigator:
          • Keisha Gibson, MD
        • Contact:
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Atrium Health Levine Children's Hospital
        • Principal Investigator:
          • Susan Massengill, MD
        • Contact:
      • Winston-Salem, North Carolina, United States, 27157
        • Withdrawn
        • Wake Forest School of Medicine
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Sub-Investigator:
          • Katherine Dell, MD
        • Contact:
        • Contact:
          • Villarreal
      • Cleveland, Ohio, United States, 44106
        • Completed
        • University Hospital Rainbow Babies & Children's Hospital
      • Cleveland, Ohio, United States, 44109
        • Completed
        • MetroHealth Hospital at Case Western Medical Center
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Wexner Medical Center
        • Contact:
        • Principal Investigator:
          • Salem Almaani, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
        • Contact:
        • Principal Investigator:
          • Lawrence Holzman, MD
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Sub-Investigator:
          • Kevin Meyers, MD
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19140
        • Recruiting
        • Temple University
        • Contact:
        • Principal Investigator:
          • Crystal Gadegbeku, MD
        • Principal Investigator:
          • Iris Lee, MD
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • David Selewski, MD, MS
    • Texas
      • Dallas, Texas, United States, 75390
      • Houston, Texas, United States, 77030
        • Recruiting
        • Texas Children's Hospital - Baylor College of Medicine
        • Contact:
        • Principal Investigator:
          • Shweta S. Shah, MD
    • Washington
      • Seattle, Washington, United States, 98195
      • Seattle, Washington, United States, 98145
      • Spokane, Washington, United States, 99204

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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.

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event rate of change in urinary protein excretion and renal function.
Time Frame: 60 months
Defined as remission, partial remission and non-remission
60 months
Rate of change in renal function.
Time Frame: 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Life:
Time Frame: 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
Time Frame: 60 months
Any cancer diagnosis of the skin, hematopoietic system, or solid organ after enrollment in NEPTUNE
60 months
Infections, Serious and Systemic
Time Frame: 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
Time Frame: 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
Time Frame: 60 months
Documented hospital admission, including observation for ≥24 hours.
60 months
Emergency Department/ Observation Unit Visit
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

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

Investigators

  • Principal Investigator: Matthias Kretzler, MD, University Of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

July 29, 2010

First Submitted That Met QC Criteria

September 23, 2010

First Posted (Estimated)

September 24, 2010

Study Record Updates

Last Update Posted (Actual)

January 5, 2024

Last Update Submitted That Met QC Criteria

January 3, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6801
  • 1U54DK083912 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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