Assess Urine Biomarkers to Predict Nephropathy in Fabry Disease

Study Overview
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Brief Summary
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The purpose of this research is to collect biological samples (urine) to develop assays for immune biomarkers to possibly in the future be able to screen subjects with Fabry disease and be able to understand better progression of nephropathy in Fabry disease and predict nephropathy in Fabry disease.

Detailed Description
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This is a study to assess the markers related to autophagy, apoptosis, pyroptosis, and inflammatory markers related to NFkB, TNF-alpha, and TGF-β1 pathways in the urine. Urinary biomarkers will then be compared to the standard measures of kidney function and proteinuria: GFR, cystatin-C, B2M, bikunin, NGAL. Gb3 and Lyso-Gb3, urine microalbumin, and urine protein-to-creatinine (UPCR) ratio. Investigators will also analyze the role of therapy, especially for the inflammatory responses in participants on stable enzyme replacement therapy (ERT) with that of patients naïve to therapy. There will be a total of 25 biomarkers that will be assessed during the study. Biomarkers of inflammation Il-4 Il-6 IL-8 Il-10 Il-12 Il-18 MCP1 TGF-β1 IFN-γ TNF-α IL-1β RANTES BAFF APRIL PAI-1 Biomarkers of kidney function and proteinuria B2M Bikunin NGAL Osteopontin Clusterin Creatinine Acute kidney injury KIM-1 YKL-40 EGF CK-18 M30

Official Title
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Pilot Study to Assess Clinical and Pivotal Biomarkers in the Urine to Predict the Progression of Nephropathy in Fabry Disease

Conditions
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Fabry Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female subject is greater than 18 but not older than 80 years. Subject willing to sign the informed consent and/or assent. Confirmed diagnosis of Fabry disease based on deficient α-Gal A enzymatic activity and molecular analysis demonstrating pathogenic variants in the GLA gene. Exclusion Criteria: Any other known genetic condition associated with CKD. Evidence of hepatitis B or C infections or other chronic infectious diseases, Pregnancy or breastfeeding. Any other chronic condition, as per PI's discretion, that makes the subject ineligible.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fabry patients without clinical evidence of nephropathy<br>No deterioration of kidney function. | |
| Fabry patients with clinical evidence of nephropathy<br>Deterioration of kidney function. | |
| Naïve Fabry patients<br>These patients have no received treatment. | |
| Healthy controls<br>Not diagnosed with Fabry disease. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| identify urinary inflammatory biomarkers associated with nephropathy in Fabry disease, Units pg/ml | IL-1β, TNF-α, IL-6, Il-4, IL-8, Il-10, Il-12, Il-18, MCP1, RANTES, BAFF, APRIL, TGF-β1, INF-gamma, and PAI-1will be measured in urine. | through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify biomarkers of renal glomerular function, tubular injury and endothelial dysfunction. Units pg/ml | B2M, GFR, albumin, cystatin C, osteopontin, clusterin, creatinine, EGF, NGAL, KIM-1, alpha-1-microglobulin, bikunin, YKL-40, CK-18 M30. | through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urine collection, biomarkers, CKD, Early detection