{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:05:40Z","timestamp":1791993940080,"version":"4.4.0"},"reference-count":121,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["P1-0170"],"award-info":[{"award-number":["P1-0170"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Progressive nephropathy is one of the main features of Fabry disease, which largely contributes to the overall morbidity and mortality burden of the disease. Due to the lack of specific biomarkers, the heterogeneity of the disease, and unspecific symptoms, diagnosis is often delayed. Clinical presentation in individual patients varies widely, even in patients from the same family carrying the same pathogenic GLA variant. Therefore, it is reasonable to anticipate that additional genomic, transcriptomic, proteomic, and metabolomics factors influence the manifestation and progression of the disease. The aim of this article is to provide an overview of nephropathy in Fabry patients and the biomarkers currently used in the diagnosis and follow-up. Current biomarkers are associated with late signs of kidney damage. Therefore, there is a need to identify biomarkers associated with early stages of kidney damage that would enable early diagnosis, which is crucial for effective treatment and prevention of severe irreversible complications. Recent advances in sequencing and -omics technologies have led to several studies investigating new biomarkers. We will provide an overview of the novel biomarkers, critically evaluate their clinical utility, and propose future perspectives, which we believe might be in their integration.<\/jats:p>","DOI":"10.3390\/genes11091091","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T10:22:23Z","timestamp":1600424543000},"page":"1091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Biomarkers of Fabry Nephropathy: Review and Future Perspective"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-1084","authenticated-orcid":false,"given":"Tina","family":"Levstek","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-9606","authenticated-orcid":false,"given":"Bojan","family":"Vujkovac","sequence":"additional","affiliation":[{"name":"Centre for Fabry Disease, General Hospital Slovenj Gradec, Gosposvetska cesta 1, 2380 Slovenj Gradec, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-3547","authenticated-orcid":false,"given":"Katarina","family":"Trebusak Podkrajsek","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"},{"name":"Clinical Institute for Special Laboratory Diagnostics, University Children\u2019s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1056\/NEJM196705252762101","article-title":"Enzymatic Defect in Fabry\u2019s Disease. Ceramidetrihexosidase Deficiency","volume":"276","author":"Brady","year":"1967","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF00446279","article-title":"Characterization of \u03b1-galactosidase isoenzymes in normal and Fabry human-Chinese Hamster somatic cell hybrids","volume":"36","author":"Hamers","year":"1977","journal-title":"Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1073\/pnas.0712309105","article-title":"Elevated globotriaosylsphingosine is a hallmark of Fabry disease","volume":"105","author":"Aerts","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.bbadis.2010.05.003","article-title":"Plasma globotriaosylsphingosine: Diagnostic value and relation to clinical manifestations of Fabry disease","volume":"1802","author":"Rombach","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s00428-007-0468-6","article-title":"Cellular and tissue localization of globotriaosylceramide in Fabry disease","volume":"451","author":"Askari","year":"2007","journal-title":"Virchows Arch."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2147\/TACG.S146022","article-title":"Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype-phenotype correlations","volume":"12","author":"Oliveira","year":"2019","journal-title":"Appl. Clin. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1136\/jmg.2008.065904","article-title":"Natural course of Fabry disease: Changing pattern of causes of death in FOS - Fabry Outcome Survey","volume":"46","author":"Mehta","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.kint.2016.10.004","article-title":"Screening, diagnosis, and management of patients with Fabry disease: Conclusions from a \u201cKidney Disease: Improving Global Outcomes\u201d (KDIGO) Controversies Conference","volume":"91","author":"Schiffmann","year":"2017","journal-title":"Kidney Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s10545-006-0196-0","article-title":"Manifestations of Fabry disease in placental tissue","volume":"29","author":"Vedder","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/0002-9378(90)90410-9","article-title":"Demonstration of Fabry\u2019s disease deposits in placenta","volume":"162","author":"Popli","year":"1990","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Desnick, R.J. (2015). Fabry Disease: \u03b1-Galactosidase A Deficiency. Rosenberg\u2019s Molecular and Genetic Basis of Neurological and Psychiatric Disease: Fifth Edition, Academic Press.","DOI":"10.1016\/B978-0-12-410529-4.00038-3"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1136\/jmg.33.8.682","article-title":"Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the \u03b1-galactosidase A gene","volume":"33","author":"Jansen","year":"1996","journal-title":"J. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s00109-005-0656-2","article-title":"Relationship between X-inactivation and clinical involvement in Fabry heterozygotes. Eleven novel mutations in the \u03b1-galactosidase a gene in the Czech and Slovak population","volume":"83","author":"Dobrovolny","year":"2005","journal-title":"J. Mol. Med."},{"key":"ref_15","first-page":"100529","article-title":"Comment: Why are females with Fabry disease affected?","volume":"21","author":"Beck","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ymgme.2007.09.013","article-title":"Females with Fabry disease frequently have major organ involvement: Lessons from the Fabry Registry","volume":"93","author":"Wilcox","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s10545-010-9261-9","article-title":"Toward a consensus in the laboratory diagnostics of Fabry disease - recommendations of a European expert group","volume":"34","author":"Gal","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.clinbiochem.2011.03.141","article-title":"Whole-blood \u03b1-D-galactosidase A activity for the identification of Fabry\u2019s patients","volume":"44","author":"Massaccesi","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1016\/j.cca.2010.06.023","article-title":"Quantification of \u03b1-galactosidase activity in intact leukocytes","volume":"411","author":"Kovarik","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cccn.2004.10.019","article-title":"Screening for Fabry disease using whole blood spots fails to identify one-third of female carriers","volume":"353","author":"Linthorst","year":"2005","journal-title":"Clin. Chim. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s12967-016-1049-8","article-title":"Increased urinary CD80 excretion and podocyturia in Fabry disease","volume":"14","author":"Trimarchi","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s10545-006-0484-8","article-title":"The Dutch Fabry cohort: Diversity of clinical manifestations and Gb3 levels","volume":"30","author":"Vedder","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2174\/187152506778520718","article-title":"The role of ceramide trihexoside (globotriaosylceramide) in the diagnosis and follow-up of the efficacy of treatment of Fabry Disease: A review of the literature","volume":"4","author":"Bekri","year":"2008","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ymgme.2016.10.006","article-title":"Plasma LysoGb3: A useful biomarker for the diagnosis and treatment of Fabry disease heterozygotes","volume":"120","author":"Nowak","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ymgme.2010.03.020","article-title":"Plasma globotriaosylsphingosine as a biomarker of Fabry disease","volume":"100","author":"Togawa","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s10157-017-1525-3","article-title":"Plasma lyso-Gb3: A biomarker for monitoring fabry patients during enzyme replacement therapy","volume":"22","author":"Sakuraba","year":"2018","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1136\/jmedgenet-2017-104863","article-title":"Agalsidase alfa versus agalsidase \u03b2 for the treatment of Fabry disease: An international cohort study","volume":"55","author":"Arends","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: Management and treatment recommendations for adult patients","volume":"123","author":"Ortiz","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.1111\/j.1742-4658.2007.06041.x","article-title":"Active-site-specific chaperone therapy for Fabry disease. Yin and Yang of enzyme inhibitors","volume":"274","author":"Fan","year":"2007","journal-title":"FEBS J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1093\/ndt\/gfm848","article-title":"Nephropathy in males and females with Fabry disease: Cross-sectional description of patients before treatment with enzyme replacement therapy","volume":"23","author":"Ortiz","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/cge.12386","article-title":"The kidney in Fabry\u2019s disease","volume":"86","author":"Pisani","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ncpneph0806","article-title":"Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults","volume":"4","author":"Ortiz","year":"2008","journal-title":"Nat. Clin. Pract. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S134","DOI":"10.1097\/01.ASN.0000016684.07368.75","article-title":"Renal pathology in Fabry disease","volume":"13","author":"Alroy","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"44","DOI":"10.5414\/CNP88FX28","article-title":"Fabry disease: Diagnostic methods in nephrology practice","volume":"88","author":"Vujkovac","year":"2017","journal-title":"Clin. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1053\/j.ajkd.2007.12.032","article-title":"Renal biopsy findings in children and adolescents with Fabry disease and minimal albuminuria","volume":"51","author":"Bostad","year":"2008","journal-title":"Am. J. Kidney Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrneph.2014.114","article-title":"Inflammatory processes in renal fibrosis","volume":"10","author":"Meng","year":"2014","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nrneph.2015.215","article-title":"Renal fibrosis in 2015: Understanding the mechanisms of kidney fibrosis","volume":"12","author":"Zhou","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1681\/ASN.2008030287","article-title":"New equations to estimate GFR in children with CKD","volume":"20","author":"Schwartz","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000493469","article-title":"Glomerular hyperfiltration: An early marker of nephropathy in Fabry disease","volume":"141","author":"Riccio","year":"2019","journal-title":"Nephron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2215\/CJN.08091109","article-title":"Assessment of renal pathology and dysfunction in pediatric patients with Fabry disease","volume":"5","author":"Ramaswami","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1093\/ndt\/gfp031","article-title":"Fabry disease: Progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy","volume":"24","author":"Schiffmann","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ymgme.2011.06.021","article-title":"Cystatin C and NT-proBNP as prognostic biomarkers in Fabry disease","volume":"104","author":"Olivera","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/ajcp\/82.1.24","article-title":"Immunohistochemical localization of glycosphingolipid in urinary renal tubular cells in Fabry\u2019s disease","volume":"82","author":"Chatterjee","year":"1984","journal-title":"Am. J. Clin. Pathol"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1346-8138.1985.tb01540.x","article-title":"Concentric lamellar spheres in urine from a female carrier of and patients with Fabry\u2019s disease\u2014With special reference to polarization and electron microscopic comparison with nephrotic syndrome","volume":"12","author":"Nagao","year":"1985","journal-title":"J. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1056\/NEJM197104082841401","article-title":"Diagnosis of glycosphingolipidoses by urinary-sediment analysis","volume":"284","author":"Desnick","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1093\/ndt\/gfr084","article-title":"Targeted urine microscopy in Anderson-Fabry disease: A cheap, sensitive and specific diagnostic technique","volume":"26","author":"Selvarajah","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ymgme.2014.08.007","article-title":"Chronic kidney disease and an uncertain diagnosis of Fabry disease: Approach to a correct diagnosis","volume":"114","author":"Svarstad","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.2215\/CJN.01820217","article-title":"Long-term dose-dependent agalsidase effects on kidney histology in Fabry disease","volume":"12","author":"Skrunes","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1093\/ndt\/gfp528","article-title":"Scoring system for renal pathology in Fabry disease: Report of the International Study Group of Fabry Nephropathy (ISGFN)","volume":"25","author":"Fogo","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ymgme.2019.03.010","article-title":"Low-dose agalsidase \u03b2 treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial","volume":"127","author":"Ramaswami","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/ki.2010.484","article-title":"Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease","volume":"79","author":"Najafian","year":"2011","journal-title":"Kidney Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00428-008-0653-2","article-title":"Kidney biopsy findings in heterozygous Fabry disease females with early nephropathy","volume":"453","author":"Valbuena","year":"2008","journal-title":"Virchows Arch."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/modpathol.3800634","article-title":"Fabry disease: A morphologic study of 11 cases","volume":"19","author":"Fischer","year":"2006","journal-title":"Mod. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000479751","article-title":"Bedside stereomicroscopy of Fabry kidney biopsies: An easily available method for diagnosis and assessment of sphingolipid deposits","volume":"138","author":"Svarstad","year":"2018","journal-title":"Nephron"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1046\/j.1523-1755.2002.00675.x","article-title":"Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy","volume":"62","author":"Thurberg","year":"2002","journal-title":"Kidney Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1681\/ASN.2006080816","article-title":"Sustained, long-term renal stabilization after 54 months of agalsidase \u03b2 therapy in patients with Fabry disease","volume":"18","author":"Germain","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.2147\/DDDT.S207856","article-title":"Cardio-renal outcomes with long-term agalsidase alfa enzyme replacement therapy: A 10-year Fabry Outcome Survey (FOS) analysis","volume":"13","author":"Ramaswami","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/ehf2.12647","article-title":"Cardiomyopathy and kidney function in agalsidase \u03b2-treated female Fabry patients: A pre-treatment vs. post-treatment analysis","volume":"7","author":"Wanner","year":"2020","journal-title":"ESC Hear. Fail."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1681\/ASN.2006111263","article-title":"Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing","volume":"18","author":"Schiffmann","year":"2007","journal-title":"J. Am. Soc. Nephrol"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.2215\/CJN.04340510","article-title":"Prognostic indicators of renal disease progression in adults with fabry disease: Natural history data from the Fabry Registry","volume":"5","author":"Wanner","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1038\/sj.ki.5001794","article-title":"Predicting initiation and progression of chronic kidney disease: Developing renal risk scores","volume":"70","author":"Taal","year":"2006","journal-title":"Kidney Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/sj.ejhg.5201184","article-title":"Remarkable variability in renal disease in a large Slovenian family with Fabry disease","volume":"12","author":"Verovnik","year":"2004","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"205948","DOI":"10.1155\/2013\/205948","article-title":"Urine bikunin as a marker of renal impairment in Fabry\u2019s disease","volume":"2013","author":"Lepedda","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ymgme.2017.05.007","article-title":"New biomarkers defining a novel early stage of Fabry nephropathy: A diagnostic test study","volume":"121","author":"Aguiar","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"360","DOI":"10.2215\/CJN.06090809","article-title":"Biomarkers of Fabry disease nephropathy","volume":"5","author":"Schiffmann","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1093\/ndt\/gft452","article-title":"Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease","volume":"29","author":"Prabakaran","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/s10545-008-0900-3","article-title":"Abnormal expression and processing of uromodulin in Fabry disease reflects tubular cell storage alteration and is reversible by enzyme replacement therapy","volume":"31","author":"Elleder","year":"2008","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000369309","article-title":"Foot process effacement is an early marker of nephropathy in young classic Fabry patients without albuminuria","volume":"129","author":"Kanai","year":"2015","journal-title":"Nephron"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Fall, B., Scott, C.R., Mauer, M., Shankland, S., Pippin, J., Jefferson, J.A., Wallace, E., Warnock, D., and Najafian, B. (2016). Urinary podocyte loss is increased in patients with Fabry disease and correlates with clinical severity of Fabry nephropathy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168346"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1681\/ASN.2019050497","article-title":"Accumulation of globotriaosylceramide in podocytes in Fabry nephropathy is associated with progressive podocyte loss","volume":"31","author":"Najafian","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/ckj\/sfy053","article-title":"Early decrease in the podocalyxin to synaptopodin ratio in urinary Fabry podocytes","volume":"12","author":"Trimarchi","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3389\/fendo.2014.00148","article-title":"Podocyte dedifferentiation: A specialized process for a specialized cell","volume":"5","author":"May","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1750-1172-8-116","article-title":"Fibrosis: A key feature of Fabry disease with potential therapeutic implications","volume":"8","author":"Weidemann","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"49","DOI":"10.5935\/0101-2800.20160008","article-title":"Podocyturia in Fabry disease","volume":"38","author":"Pereira","year":"2016","journal-title":"J. Bras. Nefrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s10545-007-0716-6","article-title":"Correlation between interleukin-6 promoter and C-reactive protein (CRP) polymorphisms and CRP levels with the Mainz Severity Score Index for Fabry disease","volume":"31","author":"Altarescu","year":"2008","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1212\/01.WNL.0000166000.24321.4F","article-title":"Effect of genetic modifiers on cerebral lesions in Fabry disease","volume":"64","author":"Altarescu","year":"2005","journal-title":"Neurology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1034\/j.1399-0004.2002.610605.x","article-title":"Endothelial nitric oxide synthase gene polymorphisms in Fabry\u2019s disease","volume":"61","author":"Heltianu","year":"2002","journal-title":"Clin. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"107558","DOI":"10.18632\/oncotarget.22505","article-title":"Genetic variants associated with Fabry disease progression despite enzyme replacement therapy","volume":"8","author":"Scionti","year":"2017","journal-title":"Oncotarget"},{"key":"ref_80","first-page":"4980942","article-title":"High Lyso-Gb3 plasma levels associated with decreased miR-29 and miR-200 urinary excretion in young non-albuminuric male patient with classic Fabry disease","volume":"2019","author":"Jaurretche","year":"2019","journal-title":"Case Rep. Nephrol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4236\/ojneph.2018.83009","article-title":"Urinary excretion of microRNAs in young Fabry disease patients with mild or absent nephropathy","volume":"8","author":"Jaurretche","year":"2018","journal-title":"Open J. Nephrol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"15277","DOI":"10.1038\/s41598-019-51805-6","article-title":"Circulating microRNAs in Fabry disease","volume":"9","author":"Xiao","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Condrat, C.E., Thompson, D.C., Barbu, M.G., Bugnar, O.L., Boboc, A., Cretoiu, D., Suciu, N., Cretoiu, S.M., and Voinea, S.C. (2020). miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells, 9.","DOI":"10.3390\/cells9020276"},{"key":"ref_84","first-page":"1","article-title":"Aberrant DNA methylation of calcitonin receptor in Fabry patients treated with enzyme replacement therapy","volume":"5","author":"Metz","year":"2015","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_85","first-page":"100497","article-title":"Future clinical and biochemical predictions of Fabry disease in females by methylation studies of the GLA gene","volume":"20","author":"Hossain","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cca.2015.11.018","article-title":"Tandem mass spectrometry multiplex analysis of methylated and non-methylated urinary Gb3 isoforms in Fabry disease patients","volume":"452","author":"Abaoui","year":"2016","journal-title":"Clin. Chim. Acta"},{"key":"ref_87","first-page":"239204","article-title":"Proteomics: Challenges, Techniques and Possibilities to Overcome Biological Sample Complexity","volume":"1","author":"Chandramouli","year":"2009","journal-title":"Hum. Genom. Proteom."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1002\/jcp.24002","article-title":"Challenges and Opportunities of Metabolomics","volume":"227","author":"Johnson","year":"2012","journal-title":"J. Cell Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1021\/ac203433e","article-title":"Urinary globotriaosylsphingosine-related biomarkers for Fabry disease targeted by metabolomics","volume":"84","author":"Boutin","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9039","DOI":"10.1021\/ac401542k","article-title":"A metabolomic study to identify new globotriaosylceramide-related biomarkers in the plasma of Fabry disease patients","volume":"85","author":"Manwaring","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"280","DOI":"10.2174\/092986713804806685","article-title":"A metabolomic study reveals novel plasma lyso-Gb3 analogs as Fabry disease biomarkers","volume":"20","author":"Dupont","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1093\/ndt\/gfq306","article-title":"Globotriaosylsphingosine actions on human glomerular podocytes: Implications for Fabry nephropathy","volume":"26","author":"Sanz","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ymgme.2017.09.004","article-title":"Contribution of inflammatory pathways to Fabry disease pathogenesis","volume":"122","author":"Rozenfeld","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1872214809666150302104542","article-title":"Abatacept and glomerular diseases: The open road for the second signal as a new target is settled down","volume":"9","author":"Trimarchi","year":"2015","journal-title":"Recent Pat. Endocr. Metab. Immune Drug Discov."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3109\/08923973.2015.1127382","article-title":"TGF-\u03b2: The connecting link between nephropathy and fibrosis","volume":"38","author":"Sutariya","year":"2016","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cytogfr.2012.08.001","article-title":"MIF, CD74 and other partners in kidney disease: Tales of a promiscuous couple","volume":"24","author":"Sanz","year":"2013","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.cca.2010.07.038","article-title":"How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?","volume":"411","author":"Ntwari","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1021\/ac404000d","article-title":"Multiplex tandem mass spectrometry analysis of novel plasma lyso-Gb3-related analogues in Fabry disease","volume":"86","author":"Boutin","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.cca.2019.10.005","article-title":"The clinical utility of total concentration of urinary globotriaosylsphingosine plus its analogues in the diagnosis of Fabry disease","volume":"500","author":"Alharbi","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s13361-014-1060-3","article-title":"Metabolomic discovery of novel urinary galabiosylceramide analogs as Fabry disease biomarkers","volume":"26","author":"Boutin","year":"2015","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cca.2014.08.002","article-title":"Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry","volume":"438","author":"Blais","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tebani, A., Mauhin, W., Abily-Donval, L., Lesueur, C., Berger, M.G., Nadjar, Y., Berger, J., Benveniste, O., Lamari, F., and Lafor\u00eat, P. (2020). A proteomics-based analysis reveals predictive biological patterns in Fabry disease. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051325"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1136\/jmedgenet-2019-106030","article-title":"Rapid, proteomic urine assay for monitoring progressive organ disease in Fabry disease","volume":"57","author":"Doykov","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"11042","DOI":"10.1038\/s41598-018-29240-w","article-title":"Urine-derived cells: A promising diagnostic tool in Fabry disease patients","volume":"8","author":"Slaats","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1136\/jmedgenet-2017-104704","article-title":"Fabry disease: Characterisation of the plasma proteome pre- and post-enzyme replacement therapy","volume":"54","author":"Heo","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1039\/C4MB00707G","article-title":"Early markers of Fabry disease revealed by proteomics","volume":"11","author":"Matafora","year":"2015","journal-title":"Mol. Biosyst."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/ejhf.230","article-title":"Gender-specific plasma proteomic biomarkers in patients with Anderson-Fabry disease","volume":"17","author":"Hollander","year":"2015","journal-title":"Eur. J. Heart Fail."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1039\/c3mb25402j","article-title":"Alteration of proteomic profiles in PBMC isolated from patients with Fabry disease: Preliminary findings","volume":"9","author":"Cigna","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1021\/pr301200e","article-title":"The identification of new biomarkers for identifying and monitoring kidney disease and their translation into a rapid mass spectrometry-based test: Evidence of presymptomatic kidney disease in pediatric Fabry and type-I diabetic patients","volume":"12","author":"Manwaring","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Kistler, A.D., Siwy, J., Breunig, F., Jeevaratnam, P., Scherl, A., Mullen, W., Warnock, D.G., Wanner, C., Hughes, D.A., and Mischak, H. (2011). A distinct urinary biomarker pattern characteristic of female Fabry patients that mirrors response to enzyme replacement therapy. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020534"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.3109\/0886022X.2010.516859","article-title":"Study of urinary proteomes in Anderson-Fabry disease","volume":"32","author":"Zima","year":"2010","journal-title":"Ren. Fail."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1073\/pnas.0611315104","article-title":"Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities","volume":"104","author":"Moore","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1016\/j.bbadis.2019.07.005","article-title":"Global glycosphingolipid analysis in urine and plasma of female Fabry disease patients","volume":"1865","author":"Heywood","year":"2019","journal-title":"Biochim. Biophys. Acta\u2014Mol. Basis Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"13382","DOI":"10.1021\/acs.analchem.7b03609","article-title":"Separation and analysis of lactosylceramide, G galabiosylceramide, and globotriaosylceramide by LC-MS\/MS in urine of Fabry disease patients","volume":"89","author":"Boutin","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_115","first-page":"17","article-title":"Tandem mass spectrometry quantitation of lyso-Gb3 and six related analogs in plasma for Fabry disease patients","volume":"90","author":"Boutin","year":"2016","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Sueoka, H., Ichihara, J., Tsukimura, T., Togawa, T., and Sakuraba, H. (2015). Nano-LC-MS\/MS for quantification of lyso-Gb3 and its analogues reveals a useful biomarker for Fabry disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127048"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1021\/ac303033v","article-title":"Multiplex analysis of novel urinary lyso-Gb3-related biomarkers for Fabry disease by tandem mass spectrometry","volume":"85","author":"Lavoie","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.2174\/092986712800784739","article-title":"Novel Gb3 isoforms detected in urine of Fabry disease patients: A metabolomic study","volume":"19","author":"Boutin","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1007\/s00125-018-4567-5","article-title":"Biomarkers of diabetic kidney disease","volume":"61","author":"Colhoun","year":"2018","journal-title":"Diabetologia"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3803\/EnM.2016.31.1.38","article-title":"How to establish clinical prediction models","volume":"31","author":"Lee","year":"2016","journal-title":"Endocrinol. Metab."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1001\/jama.2011.451","article-title":"A predictive model for progression of chronic kidney disease to kidney failure","volume":"305","author":"Tangri","year":"2011","journal-title":"JAMA\u2014J. Am. Med. Assoc."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/9\/1091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:11:22Z","timestamp":1760177482000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/9\/1091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,18]]},"references-count":121,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["genes11091091"],"URL":"https:\/\/doi.org\/10.3390\/genes11091091","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,18]]}}}