The Nephrotic Syndrome Study Network (NEPTUNE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01240564
First received: November 11, 2010
Last updated: March 14, 2014
Last verified: February 2014
  Purpose

Background:

- The Nephrotic Syndrome Study Network (NEPTUNE) is a network of multidisciplinary researchers who are investigating why kidney disease happens. NEPTUNE researchers will collect kidney tissue and other samples (for example, blood and urine) from individuals who are scheduled to have kidney biopsies to determine the cause of protein in the urine (only one kidney biopsy is necessary).

Objectives:

- To collect kidney tissue, other samples, and data /information for continuing research into kidney diseases.

Eligibility:

- Individuals at least 18 years of age who need to have a kidney biopsy to determine the cause of protein in the urine, do not have a systemic disease that is the cause of the their kidney disease, and have not received specific treatment for kidney disease.

Design:

  • This study involves a screening and baseline visit and additional followup visits after the kidney biopsy.
  • Participants will be screened with a medical history and physical examination, as well as blood and urine samples and collection of fingernail clippings. Participants will also complete questionnaires about their history of kidney problems.
  • During the kidney biopsy, performed at the NIH Clinical Center, researchers will take an additional tissue sample for research.
  • Participants will return for followup visits at NIH every 4 months in the first year, and every 6 months in the second through fifth years after the biopsy. Additional blood and urine samples will be collected at each visit, and fingernail clippings will also be collected annually by the study researchers.
  • Treatment for kidney disease will not be provided as part of this protocol and instead will generally be provided by the patient s own physician.

Compensation:

Subjects received compensation for each visit to the NIH Clinical Center.


Condition
Kidney Disease
Nephrotic Syndrome
Glomerular Disease
Glomerulonephritis
Glomerulosclerosis, Focal

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Nephrotic Syndrome Study Network (NEPTUNE)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 1) Event rate of change in urinary proteinuria excretion. 2) Rate of change in renal function: 25mls/min/1.73m2 reduction, 50% decline in follow-up eGFR, end stage renal disease.

Secondary Outcome Measures:
  • 1) Quality of life2) New Onset Diabetes

Estimated Enrollment: 750
Study Start Date: October 2010
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 (1). 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA

Inclusion Criteria for the FSGS/MCD Cohort

  • A new diagnosis of FSGS or MCD according to characteristic light, electron (EM), and immunofluorescence microscopy (IM), with presence of at least five glomeruli per biopsy available for analysis. Biopsy slides will be reviewed and diagnosis confirmed by 2 study pathologists according to standardized criteria developed by the pathology committee;
  • Documented urinary protein excretion greater than or equal to 500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.

Inclusion criteria for the MN Cohort

  • A new diagnosis of MN according to characteristic light, electron (EM), and immunofluorescence microscopy (IM), with presence of diagnostic changes in at least one glomerulus per biopsy. Biopsy slides will be reviewed and diagnosis confirmed by 2 study pathologists according to standardized criteria developed by the pathology committee
  • Documented urinary protein excretion greater than or equal to 500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.

Inclusion criteria for the OG Cohort

  • A new diagnosis of glomerulopathy according to characteristic light, electron (EM), and immunofluorescence microscopy (IM), with presence of diagnostic changes in at least one glomerulus per biopsy. Biopsy slides will be reviewed and diagnosis confirmed by 2 study pathologists according to standardized criteria developed by the pathology committee;
  • Documented urinary protein excretion greater than or equal to 500 mg/24 hours or spot protein:creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.

EXCLUSION CRITERIA

Exclusion criteria for the FSGS/MCD and MN Cohorts

  • Prior solid organ transplant
  • A clinical diagnosis of FSGS/MCD or MN 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
  • Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-uretheral reflux or renal dysplasia)
  • Known systemic disease diagnosis at time of enrollment with 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)
  • Laboratory information unavailable prior to consent and biopsy procedure subsequently supporting exclusion criteria will deem a participant ineligible.

Exclusion Criteria for the Other Glomerulopathies

  • 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
  • Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-uretheral 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)
  • Laboratory information unavailable prior to consent and biopsy procedure subsequently supporting exclusion criteria will deem a participant ineligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01240564

Contacts
Contact: Anaida Widell (301) 451-9946 awidell@cc.nih.gov
Contact: Jeffrey B Kopp, M.D. (301) 594-3403 jeffreyk@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey B Kopp, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01240564     History of Changes
Other Study ID Numbers: 110023, 11-DK-0023
Study First Received: November 11, 2010
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Proteinuria
Focal Segmental Glomerulosclerosis
Membranous Nephropathy
Chronic Kidney Disease
Kidney Disease
Nephrotic Syndrome
Glomerulonephritis
Glomerulosclerosis
FSGS

Additional relevant MeSH terms:
Glomerulonephritis
Glomerulosclerosis, Focal Segmental
Kidney Diseases
Nephrotic Syndrome
Nephritis
Urologic Diseases
Nephrosis

ClinicalTrials.gov processed this record on July 26, 2014