title: Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease.
abstract: Progressive renal failure often complicates Fabry disease, the pathogenesis of which is not well understood. To further explore this we applied unbiased stereological quantitative methods to electron microscopic changes of Fabry nephropathy and the relationship between parameters of glomerular structure and renal function in 14 young Fabry patients (median age 12 years). Renal biopsies were obtained shortly before enzyme replacement therapy from these patients and from nine normal living kidney donors as controls. Podocyte globotriaosylceramide (GL-3) inclusion volume density increased progressively with age; however, there were no significant relationships between age and endothelial or mesangial inclusion volume densities. Foot process width, greater in male Fabry patients, also progressively increased with age compared with the controls, and correlated directly with proteinuria. In comparison to the biopsies of the controls, endothelial fenestration was reduced in Fabry patients. Thus, our study found relationships between quantitative parameters of glomerular structure in Fabry nephropathy and age, as well as urinary protein excretion. Hence, podocyte injury may play a pivotal role in the development and progression of Fabry nephropathy.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA. Electronic address: najafian@u.washington.edu.
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway; Institute of Medicine, University of Bergen, Bergen, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Svarstad
authors.affiliation: Department of Pathology, University of Bergen, Bergen, Norway; Institute of Gade, University of Bergen, Bergen, Norway.
authors.forename: Leif
authors.initials: L
authors.lastname: Bostad
authors.affiliation: INSERM, U983, Université René Descartes, Hôpital Necker-Enfants Malades AP-HP, Paris, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.affiliation: Institute of Medicine, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Tøndel
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Chester
authors.initials: C
authors.lastname: Whitley
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood / Q000652:urine; D018450:Disease Progression; D042783:Endothelial Cells / Q000737:chemistry / Q000648:ultrastructure; D005060:Europe; D000795:Fabry Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D050199:Podocytes / Q000737:chemistry* / Q000648:ultrastructure*; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051437:Renal Insufficiency / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D014281:Trihexosylceramides / Q000378:metabolism*; D014481:United States; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D003404:Creatinine