<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02994303</url>
  </required_header>
  <id_info>
    <org_study_id>51316-EA</org_study_id>
    <secondary_id>U54NS065768</secondary_id>
    <nct_id>NCT02994303</nct_id>
  </id_info>
  <brief_title>Podocyturia - Predictor of Renal Dysfunction in Fabry Nephropathy</brief_title>
  <official_title>Podocyturia, a Non-Invasive Predictor of Renal Dysfunction in Fabry Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rare Diseases Clinical Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lysosomal Disease Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In patients with Fabry disease, this research study explores the presence of podocytes in&#xD;
      their urine as a potential non-invasive biomarker for baseline kidney disease; and explores&#xD;
      changes in the quantity of podocytes in their urine over time as a predictor for kidney&#xD;
      disease progression. To accomplish this, the investigators will evaluate the quantification&#xD;
      of podocytes in the urine of Fabry disease patients at baseline and longitudinally over time.&#xD;
      This study requires a single patient visit, during which the patient provides a urine&#xD;
      specimen. The research team will then collect the patient's kidney function data proximate to&#xD;
      the time of urine collection, and follow the patient's kidney function data longitudinally&#xD;
      over the five years of this study by reviewing their medical charts. The study offers no&#xD;
      interventions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite long-term recombinant enzyme replacement therapy, kidney failure remains a common and&#xD;
      important complication of Fabry disease. Recent studies suggest that early administration of&#xD;
      enzyme replacement therapy in sufficient dosage may prevent progression of kidney failure in&#xD;
      patients with Fabry disease. Currently, there is no reliable non-invasive biomarker to detect&#xD;
      early, occult kidney injury in these patients. Such early kidney injury detection is critical&#xD;
      for guiding the decision as to when to initiate enzyme replacement therapy, and for&#xD;
      identifying those patients with more severe kidney injury who may need higher doses of enzyme&#xD;
      replacement therapy or additional forms of therapy.&#xD;
&#xD;
      Podocytes are special kidney cells with a crucial role in preventing escape of protein from&#xD;
      the blood into the urine. Biopsy studies of Fabry disease patients suggest that podocyte&#xD;
      injury occurs early and is progressive with increasing age in young Fabry disease patients.&#xD;
      It is also likely that podocyte injury and loss leads to irreversible kidney lesions in later&#xD;
      stages of Fabry disease nephropathy. Because injured podocytes are sloughed off into the&#xD;
      urine (a manifestation known as podocyturia), quantification of urine podocytes might serve&#xD;
      as a non-invasive and sensitive biomarker useful for predicting Fabry disease nephropathy&#xD;
      risk; and to guide more effective Fabry disease treatment.&#xD;
&#xD;
      The investigators' preliminary data show correlations between presence of urinary podocytes&#xD;
      and other markers of renal disease in adult Fabry disease patients; however, these&#xD;
      cross-sectional data need to be expanded. The investigators have no information as to whether&#xD;
      this potential biomarker could predict progression of the disease.&#xD;
&#xD;
      The investigators hypothesize that since podocyte injury plays a central role in kidney&#xD;
      complications of Fabry disease, podocyte loss detected in the urine will identify patients&#xD;
      with greater underlying kidney disease, and will identify patients with greater propensity&#xD;
      for kidney disease progression. They also hypothesize that the number of podocytes in the&#xD;
      urine of patients with Fabry disease will correlate directly with these patients'&#xD;
      proteinuria, and will correlate inversely with their glomerular filtration rate (GFR) at&#xD;
      baseline. Additionally the investigators hypothesize that the number of podocytes in the&#xD;
      urine of patients with Fabry disease will predict increase in proteinuria and decline in&#xD;
      glomerular filtration rate, as measured during long-term patient follow-up.&#xD;
&#xD;
      Data to be collected include identification of these patients' GLA gene mutation; measurement&#xD;
      of their baseline a-galactosidase A enzyme activity; their baseline age, gender, height and&#xD;
      weight; measurement of their baseline serum creatinine (SCr), eGFR, PCR and ACR; these&#xD;
      patients' family history of Fabry disease, their history of kidney or systemic diseases,&#xD;
      their medications including enzyme replacement therapy, and their medical information about&#xD;
      other complications of Fabry disease (such as cardiomyopathy, arrhythmias, neuropathy and&#xD;
      gastrointestinal problems).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">August 2019</completion_date>
  <primary_completion_date type="Anticipated">August 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Detection of Podocyturia in Subjects Diagnosed with Fabry Disease</measure>
    <time_frame>At time of enrollment</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Number of Urine Podocytes at Year 1, 2, 3, 4 and 5</measure>
    <time_frame>Annually at Year 1, Year 2, Year 3, Year 4 and Year 5</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in urine protein/creatinine ratio (PCR) at Year 1, 2, 3, 4 and 5</measure>
    <time_frame>At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in urine albumin/creatinine ratio (ACR) at Year 1, 2, 3, 4 and 5</measure>
    <time_frame>At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in estimated glomerular filtration rate (eGFR) at Year 1, 2, 3, 4 and 5</measure>
    <time_frame>At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Number of Urine Podocytes at Year 1, 2, 3, 4 or 5, Based On Subject's New Urine Sample</measure>
    <time_frame>Annually at Year 1, Year 2, Year 3, Year 4 or Year 5</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">58</enrollment>
  <condition>Fabry Disease</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Urine Sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients of any gender who have been diagnosed with Fabry disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have been diagnosed with Fabry disease&#xD;
&#xD;
          -  Patients must be between the ages of 1 day-90 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fabry disease patients who have had a renal transplant&#xD;
&#xD;
          -  Fabry disease patients who are, or have been, subjects in any investigational drug&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Behzad Najafian, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Washington Associate Professor, Pathology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Behzad Najafian, M.D.</last_name>
    <phone>206-897-5596</phone>
    <email>najafian@u.washington.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Cindy M. Tower</last_name>
    <phone>206-616-5464</phone>
    <email>cmschnei@u.washington.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dawn Laney, MS,CGC, CCRC</last_name>
      <phone>404-778-8518</phone>
      <email>dawn.laney@emory.edu</email>
    </contact>
    <investigator>
      <last_name>Dawn Laney, MS,CGC, CCRC</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Mauer, MD</last_name>
      <phone>612-624-4688</phone>
      <email>pinth001@umn.edu</email>
    </contact>
    <contact_backup>
      <last_name>Cathy A Bagne</last_name>
      <phone>612-624-4688</phone>
      <email>pinth001@umn.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Michael Mauer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cindy M. Tower</last_name>
      <phone>206-616-5464</phone>
      <email>cmschnei@u.washington.edu</email>
    </contact>
    <investigator>
      <last_name>Behzad Najafian, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.LysosomalDiseaseNetwork.org</url>
    <description>Web site of the Lysosomal Disease Network, which funds this research study. The Lysosomal Disease Network works under the auspices of the Rare Diseases Clinical Research Network.</description>
  </link>
  <link>
    <url>http://www.washington.edu</url>
    <description>Web site of the University of Washington in Seattle, Washington. This is the location of this research study's Principal Investigator and his team.</description>
  </link>
  <link>
    <url>http://www.emory.edu/home/index.html</url>
    <description>Web site of Emory University, one of the satellite locations of this research study.</description>
  </link>
  <link>
    <url>https://twin-cities.umn.edu/</url>
    <description>Web site of the University of Minnesota - Twin Cities, one of the satellite locations of this research study.</description>
  </link>
  <reference>
    <citation>Najafian B, Tondel C, Svarstad E, Sokolovkiy A, Smith K, Mauer M. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. PLoS One. 2016 Apr 15;11(4):e0152812. doi: 10.1371/journal.pone.0152812. eCollection 2016.</citation>
    <PMID>27081853</PMID>
  </reference>
  <reference>
    <citation>Najafian B, Fogo AB, Lusco MA, Alpers CE. AJKD Atlas of Renal Pathology: Fabry nephropathy. Am J Kidney Dis. 2015 Nov;66(5):e35-6. doi: 10.1053/j.ajkd.2015.08.006. No abstract available.</citation>
    <PMID>26498420</PMID>
  </reference>
  <reference>
    <citation>Wijburg FA, Benichou B, Bichet DG, Clarke LA, Dostalova G, Fainboim A, Fellgiebel A, Forcelini C, An Haack K, Hopkin RJ, Mauer M, Najafian B, Scott CR, Shankar SP, Thurberg BL, Tondel C, Tylki-Szymanska A, Ramaswami U. Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial. PLoS One. 2015 May 8;10(5):e0124987. doi: 10.1371/journal.pone.0124987. eCollection 2015.</citation>
    <PMID>25955246</PMID>
  </reference>
  <reference>
    <citation>Mauer M, Glynn E, Svarstad E, Tondel C, Gubler MC, West M, Sokolovskiy A, Whitley C, Najafian B. Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease. PLoS One. 2014 Nov 11;9(11):e112188. doi: 10.1371/journal.pone.0112188. eCollection 2014.</citation>
    <PMID>25386848</PMID>
  </reference>
  <reference>
    <citation>Najafian B, Mauer M, Hopkin RJ, Svarstad E. Renal complications of Fabry disease in children. Pediatr Nephrol. 2013 May;28(5):679-87. doi: 10.1007/s00467-012-2222-9. Epub 2012 Aug 17.</citation>
    <PMID>22898981</PMID>
  </reference>
  <reference>
    <citation>Najafian B, Mauer M. Quantitating glomerular endothelial fenestration: an unbiased stereological approach. Am J Nephrol. 2011;33 Suppl 1(Suppl 1):34-9. doi: 10.1159/000327075. Epub 2011 Jun 10.</citation>
    <PMID>21659733</PMID>
  </reference>
  <reference>
    <citation>Najafian B, Svarstad E, Bostad L, Gubler MC, Tondel C, Whitley C, Mauer M. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int. 2011 Mar;79(6):663-670. doi: 10.1038/ki.2010.484. Epub 2010 Dec 15.</citation>
    <PMID>21160462</PMID>
  </reference>
  <reference>
    <citation>Ramaswami U, Najafian B, Schieppati A, Mauer M, Bichet DG. Assessment of renal pathology and dysfunction in children with Fabry disease. Clin J Am Soc Nephrol. 2010 Feb;5(2):365-70. doi: 10.2215/CJN.08091109. Epub 2010 Jan 7.</citation>
    <PMID>20056758</PMID>
  </reference>
  <reference>
    <citation>Mauer M, Najafian B. Implications of early renal changes in Fabry disease. Clin Ther. 2008;30 Suppl B:S40. doi: 10.1016/s0149-2918(08)80034-3. No abstract available.</citation>
    <PMID>18395133</PMID>
  </reference>
  <reference>
    <citation>Hopkin RJ, Cabrera G, Charrow J, Lemay R, Martins AM, Mauer M, Ortiz A, Patel MR, Sims K, Waldek S, Warnock DG, Wilcox WR. Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry. Mol Genet Metab. 2016 Sep;119(1-2):151-9. doi: 10.1016/j.ymgme.2016.06.007. Epub 2016 Jun 13.</citation>
    <PMID>27510433</PMID>
  </reference>
  <reference>
    <citation>Hopkin RJ, Jefferies JL, Laney DA, Lawson VH, Mauer M, Taylor MR, Wilcox WR; Fabry Pediatric Expert Panel. The management and treatment of children with Fabry disease: A United States-based perspective. Mol Genet Metab. 2016 Feb;117(2):104-13. doi: 10.1016/j.ymgme.2015.10.007. Epub 2015 Oct 23.</citation>
    <PMID>26546059</PMID>
  </reference>
  <reference>
    <citation>Warnock DG, Mauer M. Fabry disease: dose matters. J Am Soc Nephrol. 2014 Apr;25(4):653-5. doi: 10.1681/ASN.2013121322. Epub 2014 Feb 20. No abstract available.</citation>
    <PMID>24556355</PMID>
  </reference>
  <results_reference>
    <citation>Fall B, Scott CR, Mauer M, Shankland S, Pippin J, Jefferson JA, Wallace E, Warnock D, Najafian B. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy. PLoS One. 2016 Dec 16;11(12):e0168346. doi: 10.1371/journal.pone.0168346. eCollection 2016.</citation>
    <PMID>27992580</PMID>
  </results_reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>August 25, 2017</last_update_submitted>
  <last_update_submitted_qc>August 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Behzad Najafian</investigator_full_name>
    <investigator_title>Associate Professor, Director, Electron Microscopy Laboratory</investigator_title>
  </responsible_party>
  <keyword>Fabry disease</keyword>
  <keyword>Fabry nephropathy</keyword>
  <keyword>end-stage renal disease</keyword>
  <keyword>Anderson-Fabry disease</keyword>
  <keyword>Fabry's disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</mesh_term>
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management &amp; Coordinating Center (&quot;DMCC&quot;). Eventually this data will become part of the database of Genotypes and Phenotypes (&quot;dbGaP&quot;), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02994303
org study id: 51316-EA
secondary id: U54NS065768
nct id: NCT02994303
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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).
observational model: Case-Only
time perspective: Prospective
measure: Detection of Podocyturia in Subjects Diagnosed with Fabry Disease
time frame: At time of enrollment
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
Urine Sample
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 90 Years
healthy volunteers: No
last name: Behzad Najafian, M.D.
role: Principal Investigator
affiliation: University of Washington Associate Professor, Pathology
last name: Behzad Najafian, M.D.
phone: 206-897-5596
email: najafian@u.washington.edu
last name: Cindy M. Tower
phone: 206-616-5464
email: cmschnei@u.washington.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.LysosomalDiseaseNetwork.org
description: Web site of the Lysosomal Disease Network, which funds this research study. The Lysosomal Disease Network works under the auspices of the Rare Diseases Clinical Research Network.
url: http://www.washington.edu
description: Web site of the University of Washington in Seattle, Washington. This is the location of this research study's Principal Investigator and his team.
url: http://www.emory.edu/home/index.html
description: Web site of Emory University, one of the satellite locations of this research study.
url: https://twin-cities.umn.edu/
description: Web site of the University of Minnesota - Twin Cities, one of the satellite locations of this research study.
citation: Najafian B, Tondel C, Svarstad E, Sokolovkiy A, Smith K, Mauer M. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. PLoS One. 2016 Apr 15;11(4):e0152812. doi: 10.1371/journal.pone.0152812. eCollection 2016.
PMID: 27081853
citation: Najafian B, Fogo AB, Lusco MA, Alpers CE. AJKD Atlas of Renal Pathology: Fabry nephropathy. Am J Kidney Dis. 2015 Nov;66(5):e35-6. doi: 10.1053/j.ajkd.2015.08.006. No abstract available.
PMID: 26498420
citation: Wijburg FA, Benichou B, Bichet DG, Clarke LA, Dostalova G, Fainboim A, Fellgiebel A, Forcelini C, An Haack K, Hopkin RJ, Mauer M, Najafian B, Scott CR, Shankar SP, Thurberg BL, Tondel C, Tylki-Szymanska A, Ramaswami U. Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial. PLoS One. 2015 May 8;10(5):e0124987. doi: 10.1371/journal.pone.0124987. eCollection 2015.
PMID: 25955246
citation: Mauer M, Glynn E, Svarstad E, Tondel C, Gubler MC, West M, Sokolovskiy A, Whitley C, Najafian B. Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease. PLoS One. 2014 Nov 11;9(11):e112188. doi: 10.1371/journal.pone.0112188. eCollection 2014.
PMID: 25386848
citation: Najafian B, Mauer M, Hopkin RJ, Svarstad E. Renal complications of Fabry disease in children. Pediatr Nephrol. 2013 May;28(5):679-87. doi: 10.1007/s00467-012-2222-9. Epub 2012 Aug 17.
PMID: 22898981
citation: Najafian B, Mauer M. Quantitating glomerular endothelial fenestration: an unbiased stereological approach. Am J Nephrol. 2011;33 Suppl 1(Suppl 1):34-9. doi: 10.1159/000327075. Epub 2011 Jun 10.
PMID: 21659733
citation: Najafian B, Svarstad E, Bostad L, Gubler MC, Tondel C, Whitley C, Mauer M. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int. 2011 Mar;79(6):663-670. doi: 10.1038/ki.2010.484. Epub 2010 Dec 15.
PMID: 21160462
citation: Ramaswami U, Najafian B, Schieppati A, Mauer M, Bichet DG. Assessment of renal pathology and dysfunction in children with Fabry disease. Clin J Am Soc Nephrol. 2010 Feb;5(2):365-70. doi: 10.2215/CJN.08091109. Epub 2010 Jan 7.
PMID: 20056758
citation: Mauer M, Najafian B. Implications of early renal changes in Fabry disease. Clin Ther. 2008;30 Suppl B:S40. doi: 10.1016/s0149-2918(08)80034-3. No abstract available.
PMID: 18395133
citation: Hopkin RJ, Cabrera G, Charrow J, Lemay R, Martins AM, Mauer M, Ortiz A, Patel MR, Sims K, Waldek S, Warnock DG, Wilcox WR. Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry. Mol Genet Metab. 2016 Sep;119(1-2):151-9. doi: 10.1016/j.ymgme.2016.06.007. Epub 2016 Jun 13.
PMID: 27510433
citation: Hopkin RJ, Jefferies JL, Laney DA, Lawson VH, Mauer M, Taylor MR, Wilcox WR; Fabry Pediatric Expert Panel. The management and treatment of children with Fabry disease: A United States-based perspective. Mol Genet Metab. 2016 Feb;117(2):104-13. doi: 10.1016/j.ymgme.2015.10.007. Epub 2015 Oct 23.
PMID: 26546059
citation: Warnock DG, Mauer M. Fabry disease: dose matters. J Am Soc Nephrol. 2014 Apr;25(4):653-5. doi: 10.1681/ASN.2013121322. Epub 2014 Feb 20. No abstract available.
PMID: 24556355
citation: Fall B, Scott CR, Mauer M, Shankland S, Pippin J, Jefferson JA, Wallace E, Warnock D, Najafian B. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy. PLoS One. 2016 Dec 16;11(12):e0168346. doi: 10.1371/journal.pone.0168346. eCollection 2016.
PMID: 27992580
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Behzad Najafian
investigator title: Associate Professor, Director, Electron Microscopy Laboratory
mesh term: Fabry Disease
mesh term: Kidney Diseases
mesh term: Renal Insufficiency
sharing ipd: Yes
ipd 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.