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Podocyturia - Predictor of Renal Dysfunction in Fabry Nephropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02994303
Recruitment Status : Unknown
Verified August 2017 by Behzad Najafian, University of Washington.
Recruitment status was:  Recruiting
First Posted : December 15, 2016
Last Update Posted : August 28, 2017
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
National Center for Advancing Translational Science (NCATS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Lysosomal Disease Network
Information provided by (Responsible Party):
Behzad Najafian, University of Washington

Brief Summary:
In patients with Fabry disease, this research study explores the presence of podocytes in their urine as a potential non-invasive biomarker for baseline kidney disease; and explores changes in the quantity of podocytes in their urine over time as a predictor for kidney disease progression. To accomplish this, the investigators will evaluate the quantification of podocytes in the urine of Fabry disease patients at baseline and longitudinally over time. This study requires a single patient visit, during which the patient provides a urine specimen. The research team will then collect the patient's kidney function data proximate to the time of urine collection, and follow the patient's kidney function data longitudinally over the five years of this study by reviewing their medical charts. The study offers no interventions.

Condition or disease
Fabry Disease

Detailed Description:

Despite long-term recombinant enzyme replacement therapy, kidney failure remains a common and important complication of Fabry disease. Recent studies suggest that early administration of enzyme replacement therapy in sufficient dosage may prevent progression of kidney failure in patients with Fabry disease. Currently, there is no reliable non-invasive biomarker to detect early, occult kidney injury in these patients. Such early kidney injury detection is critical for guiding the decision as to when to initiate enzyme replacement therapy, and for identifying those patients with more severe kidney injury who may need higher doses of enzyme replacement therapy or additional forms of therapy.

Podocytes are special kidney cells with a crucial role in preventing escape of protein from the blood into the urine. Biopsy studies of Fabry disease patients suggest that podocyte injury occurs early and is progressive with increasing age in young Fabry disease patients. It is also likely that podocyte injury and loss leads to irreversible kidney lesions in later stages of Fabry disease nephropathy. Because injured podocytes are sloughed off into the urine (a manifestation known as podocyturia), quantification of urine podocytes might serve as a non-invasive and sensitive biomarker useful for predicting Fabry disease nephropathy risk; and to guide more effective Fabry disease treatment.

The investigators' preliminary data show correlations between presence of urinary podocytes and other markers of renal disease in adult Fabry disease patients; however, these cross-sectional data need to be expanded. The investigators have no information as to whether this potential biomarker could predict progression of the disease.

The investigators hypothesize that since podocyte injury plays a central role in kidney complications of Fabry disease, podocyte loss detected in the urine will identify patients with greater underlying kidney disease, and will identify patients with greater propensity for kidney disease progression. They also hypothesize that the number of podocytes in the urine of patients with Fabry disease will correlate directly with these patients' proteinuria, and will correlate inversely with their glomerular filtration rate (GFR) at baseline. Additionally the investigators hypothesize that the number of podocytes in the urine of patients with Fabry disease will predict increase in proteinuria and decline in glomerular filtration rate, as measured during long-term patient follow-up.

Data to be collected include identification of these patients' GLA gene mutation; measurement of their baseline a-galactosidase A enzyme activity; their baseline age, gender, height and weight; measurement of their baseline serum creatinine (SCr), eGFR, PCR and ACR; these patients' family history of Fabry disease, their history of kidney or systemic diseases, their medications including enzyme replacement therapy, and their medical information about other complications of Fabry disease (such as cardiomyopathy, arrhythmias, neuropathy and gastrointestinal problems).

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Study Type : Observational
Estimated Enrollment : 58 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Podocyturia, a Non-Invasive Predictor of Renal Dysfunction in Fabry Nephropathy
Study Start Date : September 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases




Primary Outcome Measures :
  1. Detection of Podocyturia in Subjects Diagnosed with Fabry Disease [ Time Frame: At time of enrollment ]
    In subjects who have been diagnosed with Fabry disease, their urine sample will be examined for the presence of podocyturia at time of enrollment. If podocyturia is present, it will be quantified and recorded.


Secondary Outcome Measures :
  1. Change from Baseline in Number of Urine Podocytes at Year 1, 2, 3, 4 and 5 [ Time Frame: Annually at Year 1, Year 2, Year 3, Year 4 and Year 5 ]
    For Fabry disease patients who tested positive at time of enrollment for the presence of urine podocytes, annually during the five years of this study their medical records will be used as the information source to record their numbers of urine podocytes. This annual podocyte-count data will be analyzed to determine whether change over time has occurred in their number of urine podocytes, and if it has occurred, to examine if this change correlates with changes in urine albumin excretion, urine protein excretion or glomerular filtration rate, as extracted from electronic medical records.

  2. Change from Baseline in urine protein/creatinine ratio (PCR) at Year 1, 2, 3, 4 and 5 [ Time Frame: At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5 ]
    In patients who have been diagnosed with Fabry disease, their urine protein/creatinine ratio (PCR) will be quantified at time of enrollment; and annually thereafter for five years by collection of data from their medical chart. Their quantified podocyturia will be correlated with change in their urine protein/creatinine ratio (PCR) over time.

  3. Change from Baseline in urine albumin/creatinine ratio (ACR) at Year 1, 2, 3, 4 and 5 [ Time Frame: At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5 ]
    In patients who have been diagnosed with Fabry disease, their urine albumin/creatinine ratio (ACR) will be quantified at time of enrollment; and annually thereafter for five years by collection of data from their medical chart. Their quantified podocyturia will be correlated with change in their urine albumin/creatinine ratio (ACR) over time.

  4. Change from Baseline in estimated glomerular filtration rate (eGFR) at Year 1, 2, 3, 4 and 5 [ Time Frame: At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5 ]
    In patients who have been diagnosed with Fabry disease, their estimated glomerular filtration rate (eGFR) will be quantified at time of enrollment; and annually thereafter for five years by collection of data from their medical chart. Their quantified podocyturia will be correlated with change in their estimated glomerular filtration rate (eGFR) over time.

  5. Change from Baseline in Number of Urine Podocytes at Year 1, 2, 3, 4 or 5, Based On Subject's New Urine Sample [ Time Frame: Annually at Year 1, Year 2, Year 3, Year 4 or Year 5 ]
    Providing more than one urine sample for podocyte counting is optional in this study. For those subjects who do provide an additional urine specimen in any year of this study that is subsequent to baseline, the number of urine podocytes at baseline will be compared to the number of urine podocytes in any additional urine specimen(s) collected in years 1 through 5. This podocyte-count data will be analyzed to determine whether change over time has occurred in their number of urine podocytes, and if it has occurred, to examine if this change correlates with changes in urine albumin excretion, urine protein excretion or glomerular filtration rate, as extracted from electronic medical records.


Biospecimen Retention:   Samples Without DNA
Urine Sample


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients of any gender who have been diagnosed with Fabry disease
Criteria

Inclusion Criteria:

  • Patients must have been diagnosed with Fabry disease
  • Patients must be between the ages of 1 day-90 years

Exclusion Criteria:

  • Fabry disease patients who have had a renal transplant
  • Fabry disease patients who are, or have been, subjects in any investigational drug study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02994303


Contacts
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Contact: Behzad Najafian, M.D. 206-897-5596 najafian@u.washington.edu
Contact: Cindy M. Tower 206-616-5464 cmschnei@u.washington.edu

Locations
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United States, Georgia
Emory University Recruiting
Decatur, Georgia, United States, 30033
Contact: Dawn Laney, MS,CGC, CCRC    404-778-8518    dawn.laney@emory.edu   
Principal Investigator: Dawn Laney, MS,CGC, CCRC         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Michael Mauer, MD    612-624-4688    pinth001@umn.edu   
Contact: Cathy A Bagne    612-624-4688    pinth001@umn.edu   
Principal Investigator: Michael Mauer, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Cindy M. Tower    206-616-5464    cmschnei@u.washington.edu   
Principal Investigator: Behzad Najafian, M.D.         
Sponsors and Collaborators
University of Washington
Rare Diseases Clinical Research Network
National Center for Advancing Translational Science (NCATS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Lysosomal Disease Network
Investigators
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Principal Investigator: Behzad Najafian, M.D. University of Washington Associate Professor, Pathology
Additional Information:
Publications of Results:
Other Publications:

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Responsible Party: Behzad Najafian, Associate Professor, Director, Electron Microscopy Laboratory, University of Washington
ClinicalTrials.gov Identifier: NCT02994303    
Other Study ID Numbers: 51316-EA
U54NS065768 ( U.S. NIH Grant/Contract )
First Posted: December 15, 2016    Key Record Dates
Last Update Posted: August 28, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management & Coordinating Center ("DMCC"). Eventually this data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Behzad Najafian, University of Washington:
Fabry disease
Fabry nephropathy
end-stage renal disease
Anderson-Fabry disease
Fabry's disease
Additional relevant MeSH terms:
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Fabry Disease
Kidney Diseases
Renal Insufficiency
Urologic Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders