Podocyturia - Predictor of Renal Dysfunction in Fabry Nephropathy

NCT02994303 | Unknown DMC

• 2 other identifiers: 51316-EAU54NS065768
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 3

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.

Conditions

Fabry Disease

Keywords

Fabry disease; Fabry nephropathy; end-stage renal disease; Anderson-Fabry disease; Fabry's disease

Outcome Measures

Primary Outcomes (1)

• Detection of Podocyturia in Subjects Diagnosed with Fabry Disease

  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.

  At time of enrollment

Secondary Outcomes (5)

• Change from Baseline in Number of Urine Podocytes at Year 1, 2, 3, 4 and 5

  Annually at Year 1, Year 2, Year 3, Year 4 and Year 5

• Change from Baseline in urine protein/creatinine ratio (PCR) at Year 1, 2, 3, 4 and 5

  At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5

• Change from Baseline in urine albumin/creatinine ratio (ACR) at Year 1, 2, 3, 4 and 5

  At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5

• Change from Baseline in estimated glomerular filtration rate (eGFR) at Year 1, 2, 3, 4 and 5

  At time of enrollment, then annually at Year 1, Year 2, Year 3, Year 4 and Year 5

• Change from Baseline in Number of Urine Podocytes at Year 1, 2, 3, 4 or 5, Based On Subject's New Urine Sample

  Annually at Year 1, Year 2, Year 3, Year 4 or Year 5

Eligibility Criteria

• Age: 1 Day - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients of any gender who have been diagnosed with Fabry disease

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Washington: lead
• Rare Diseases Clinical Research Network: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Lysosomal Disease Network: collaborator

Study Sites (3)

Emory University

Decatur, Georgia, 30033, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 RESULT

Related Links

• Web site of the University of Washington in Seattle, Washington. This is the location of this research study's Principal Investigator and his team.
• Web site of Emory University, one of the satellite locations of this research study.
• Web site of the University of Minnesota - Twin Cities, one of the satellite locations of this research study.

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine Sample

MeSH Terms

Conditions

Fabry Disease; Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Behzad Najafian, M.D.

  University of Washington Associate Professor, Pathology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Behzad Najafian, M.D.

CONTACT

206-897-5596; najafian@u.washington.edu

Cindy M. Tower

CONTACT

206-616-5464; cmschnei@u.washington.edu

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Director, Electron Microscopy Laboratory

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 15, 2016
• Study Start: September 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 28, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (3)