Podocyturia - Predictor of Renal Dysfunction in Fabry Nephropathy
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| ClinicalTrials.gov Identifier: NCT02994303 |
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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
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| Condition or disease |
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| Fabry Disease |
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).
| 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 |
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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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 |
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
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
| Contact: Behzad Najafian, M.D. | 206-897-5596 | najafian@u.washington.edu | |
| Contact: Cindy M. Tower | 206-616-5464 | cmschnei@u.washington.edu |
| 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. | |
| Principal Investigator: | Behzad Najafian, M.D. | University of Washington Associate Professor, Pathology |
Publications of Results:
Other Publications:
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Fabry disease Fabry nephropathy end-stage renal disease Anderson-Fabry disease Fabry's disease |
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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 |