Clinical ResearchAgalsidase Benefits Renal Histology in Young Patients with Fabry DiseaseTøndel, Camilla*,†; Bostad, Leif‡,§; Larsen, Kristin Kampevold‡; Hirth, Asle†,‖; Vikse, Bjørn Egil*,¶; Houge, Gunnar‖,**; Svarstad, Einar*,¶ Author Information *Renal Research Group, Institute of Medicine, University of Bergen, Bergen, Norway; †Department of Pediatrics, ‡Department of Pathology, ‖Institute of Clinical Medicine, ¶Department of Medicine, and **Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; and §Institute of Gade, University of Bergen, Bergen, Norway Correspondence: Dr. Camilla Tøndel, Renal Research Group, Institute of Medicine, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway. Email: [email protected] Received March 27, 2012 Accepted October 9, 2012 Journal of the American Society of Nephrology 24(1):p 137-148, January 2013. | DOI: 10.1681/ASN.2012030316 Buy Metrics 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. Copyright © 2013 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.