title: Agalsidase benefits renal histology in young patients with Fabry disease.
abstract: The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7-33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.
authors.affiliation: Renal Research Group, Institute of Medicine, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway. camilla.tondel@med.uib.no
authors.forename: Camilla
authors.initials: C
authors.lastname: Tøndel
authors.forename: Leif
authors.initials: L
authors.lastname: Bostad
authors.forename: Kristin Kampevold
authors.initials: KK
authors.lastname: Larsen
authors.forename: Asle
authors.initials: A
authors.lastname: Hirth
authors.forename: Bjørn Egil
authors.initials: BE
authors.lastname: Vikse
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houge
authors.forename: Einar
authors.initials: E
authors.lastname: Svarstad
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D011507:Proteinuria / Q000652:urine; D011994:Recombinant Proteins; D014281:Trihexosylceramides / Q000652:urine; D055815:Young Adult; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; D014281:Trihexosylceramides; C000627036:agalsidase alfa; C018549:globotriaosylceramide; D000519:alpha-Galactosidase; C459420:agalsidase beta