Nephrotic Syndrome Study Network

Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

Sponsors

Lead Sponsor: University of Michigan

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

Source University of Michigan
Brief Summary

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

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.

Overall Status Recruiting
Start Date April 2010
Completion Date June 30, 2024
Primary Completion Date June 30, 2024
Study Type Observational
Primary Outcome
Measure Time Frame
Event rate of change in urinary protein excretion and renal function. 60 months
Rate of change in renal function. 60 months
Secondary Outcome
Measure Time Frame
Quality of Life: 60 months
Malignancies 60 months
Infections, Serious and Systemic 60 months
Thromboembolic Events 60 months
Hospitalization 60 months
Emergency Department/ Observation Unit Visit 60 months
Acute Kidney Injury 60 months
Death 60 months
New Onset Diabetes 60 months
Enrollment 1200
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Kidney Biopsy

Description: 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.

Eligibility

Sampling Method: Non-Probability Sample

Criteria:

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)

Gender: All

Minimum Age: N/A

Maximum Age: 80 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Matthias Kretzler, MD Principal Investigator University of Michigan
Overall Contact

Last Name: Chrysta C. Lienczewski, BS

Phone: 734-615-5021

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
University of Southern California-Children's Hospital | Los Angeles, California, 90227, United States Recruiting Lauren Whitted, BS 323-361-7299 [email protected] Kevin Lemley, MD, PhD Principal Investigator
Stanford University School of Medicine | Palo Alto, California, 94304, United States Recruiting Kshama Mehta, PhD 650-736-1822 [email protected] Richard Lafayette, MD Principal Investigator
Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center | Torrance, California, 90502, United States Recruiting Janine LaPage 310-222-4104 [email protected] Sharon Adler, MD Principal Investigator
University of Miami Miller School of Medicine | Miami, Florida, 33136, United States Recruiting Carlos Bidot 305-243-8973 [email protected] Alessia Fornoni, MD. PhD Principal Investigator
Emory University and Children's Healthcare of Atlanta | Atlanta, Georgia, 30322, United States Recruiting Brian Lee 404-712-9998 [email protected] Laurence Greenbaum, MD, PhD Principal Investigator
John Stroger Cook County Hospital | Chicago, Illinois, 60680, United States Recruiting Mathew Itteera 312-864-4614 [email protected] Ambarish Athavale, MD Principal Investigator
Johns Hopkins Medical Institute | Baltimore, Maryland, 21287, United States Recruiting Sara Boynton 443-287-9051 [email protected] Alicia Neu, MD Principal Investigator Michael Choi, MD Sub-Investigator
Kidney Disease Section, NIDDK, NIH | Bethesda, Maryland, 20892, United States Recruiting Evelyn Castro-Rubio 301-451-6994 [email protected] Jeffrey P. Kopp, MD Principal Investigator
CS Mott Children's Hospital, University of Michigan | Ann Arbor, Michigan, 48109, United States Recruiting Emily Herreshoff 734-232-4851 [email protected] Debbie Gipson, MD, MS Sub-Investigator
University of Michigan Medical Center | Ann Arbor, Michigan, 48109, United States Recruiting Chrysta C. Lienczewski, BS - adult 734-615-5021 [email protected] Matthias Kretzler, MD Principal Investigator
Mayo Clinic | Rochester, Minnesota, 55905, United States Recruiting Vladimir Chernitskiy, CCRC 507-255-0231 [email protected] Fernando Fervenza, MD, PhD Principal Investigator John Lieske, MD Sub-Investigator Marie C. Hogan, MD, PhD Sub-Investigator
Children's Mercy Hospital | Kansas City, Missouri, 64108, United States Recruiting Connie Haney, RN 816-234-3891 [email protected] Tarak Srivastava, MD Principal Investigator
Montefiore Medical Center | Bronx, New York, 11040, United States Recruiting Patti Flynn, RN 718-655-1120 [email protected] Frederick Kaskel, MD Principal Investigator Robert Woroniecki, MD Sub-Investigator
Cohen Children's Hospital | New Hyde Park, New York, 11040, United States Recruiting Kalli Gramma, RN 718-470-3499 [email protected] Christine Sethna, MD Principal Investigator
New York University Medical Center | New York, New York, 10010, United States Recruiting Frank Modersitzki, MPH - adult 212-686-7500 6379 [email protected] Olga Zhadnova, MD Principal Investigator Howard Trachtman, MD Principal Investigator
Bellevue Hospital | New York, New York, 10016, United States Recruiting Frank Modersitzki, MPH 212-686-7500 6379 [email protected] Laura Barisoni, MD Principal Investigator Olga Zhadnova, MD Sub-Investigator
New York University Veterans Administration | New York, New York, 10016, United States Recruiting Frank Modersitzki, MPH 212-686-7500 6379 [email protected] Laura Barisoni, MD Principal Investigator Olga Zhadnova, MD Sub-Investigator
Columbia University Medical Center | New York, New York, 10032, United States Recruiting Michael Toledo, RN 212-305-6842 [email protected] Andrew Bomback, MD, MPH Principal Investigator
University of North Carolina at Chapel Hill | Chapel Hill, North Carolina, 27599, United States Recruiting Anne Froment 919-923-1382 [email protected] Patrick H. Nachman, MD Principal Investigator Susan L. Hogan, PhD, MPH Sub-Investigator Keisha Gibson, MD Sub-Investigator
Wake Forest School of Medicine | Winston-Salem, North Carolina, 27157, United States Recruiting Mitzie Spainhour 336-716-4246 [email protected] Jen-Jar Lin, MD Principal Investigator
University Hospital Rainbow Babies & Children's Hospital | Cleveland, Ohio, 44106, United States Recruiting Marleen Schachere, RN 216-778-4321 [email protected] Katherine Dell, MD Sub-Investigator
MetroHealth Hospital at Case Western Medical Center | Cleveland, Ohio, 44109, United States Recruiting Marleen Schachere, RN 216-778-4321 [email protected] John Sedor, MI Principal Investigator
Cleveland Clinic | Cleveland, Ohio, 44195, United States Recruiting Annette Bellar, RN [email protected] Katherine Dell, MD Sub-Investigator
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania, 19104, United States Recruiting Krishna Kallem, MS 484-358-0315 [email protected] Kevin Meyers, MD Sub-Investigator
University of Pennsylvania | Philadelphia, Pennsylvania, 19104, United States Recruiting Krishna Kallem, MD - adult, MS 484-358-0315 [email protected] Lawrence Holzman, MD Principal Investigator
Temple University | Philadelphia, Pennsylvania, 19140, United States Recruiting Zoe Pfeffer, BS 215-707-4712 [email protected] Crystal Gadegbeku, MD Principal Investigator Iris Lee, MD Principal Investigator
University of Texas-Southwestern | Dallas, Texas, 75390, United States Recruiting Natalie Johnson, LVN 214-645-8263 [email protected] Kamal Sambandam, MD Principal Investigator
Seattle Children's Hospital | Seattle, Washington, 98145, United States Recruiting Megan Kelton 206-884-1372 [email protected] Sangeeta Hingorani, MD Sub-Investigator
University of Washington | Seattle, Washington, 98195, United States Recruiting Karina Klepach 203-221-3938 [email protected] Peter J. Nelson, MD Principal Investigator
Providence Medical Research Center | Spokane, Washington, 99204, United States Recruiting Ann Cooper, CCRC 509-474-4327 [email protected] Katherine Tuttle, MD Sub-Investigator
York Central Hospital | Richmond Hill, Ontario, L4C 4Z3, Canada Recruiting Tami Baker 905-508-5911 402 [email protected] Michael Pandes, MD Sub-Investigator
Scarborough Hospital | Scarborough, Ontario, M1H 3G4, Canada Recruiting Dione Rochester, BSc 416-279-0855 230 [email protected] Paul YW Tam, FRCP, FACP Sub-Investigator
Credit Valley Hospital | Toronto, Ontario, L5M 2N1, Canada Recruiting Paul Ling, MD 416-340-3514 [email protected] Phillip Boll, MD Sub-Investigator
Sunnybrook Hospital | Toronto, Ontario, M4N 3M5, Canada Recruiting Paul Ling, MD 416-340-3514 [email protected] Michelle Hladunewich, MD Principal Investigator
University Health Network | Toronto, Ontario, M5G2C4, Canada Recruiting Paul Ling, MD 416-340-3514 [email protected] Daniel Cattran, MD Principal Investigator Heather Reich, MD Sub-Investigator Michelle Hladunewich, MD Sub-Investigator
Location Countries

Canada

United States

Verification Date

November 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Michigan

Investigator Full Name: Matthias Kretzler

Investigator Title: Professor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Label: FSGS/MCD Cohort (Cohort A)

Description: 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.

Label: MN Cohort (Cohort A)

Description: 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.

Label: Other glomerulopathies cohort

Description: 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.

Label: cNEPTUNE (Cohort B)

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

Acronym NEPTUNE
Study Design Info

Observational Model: Cohort

Time Perspective: Prospective

Source: ClinicalTrials.gov