Document Detail


Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease.
MedLine Citation:
PMID:  21160462     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Behzad Najafian; Einar Svarstad; Leif Bostad; Marie-Claire Gubler; Camilla Tøndel; Chester Whitley; Michael Mauer
Publication Detail:
Type:  Journal Article; Multicenter Study     Date:  2010-12-15
Journal Detail:
Title:  Kidney international     Volume:  79     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-01     Completed Date:  2011-06-13     Revised Date:  2013-05-06    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  663-70     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Washington, Seattle, Washington, USA. najafian@u.washington.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Age Factors
Biological Markers / blood,  urine
Biopsy
Case-Control Studies
Child
Child, Preschool
Creatinine / blood,  urine
Disease Progression
Endothelial Cells / chemistry,  ultrastructure
Europe
Fabry Disease / complications*,  metabolism,  pathology,  physiopathology
Female
Glomerular Filtration Rate
Humans
Kidney Glomerulus / blood supply,  chemistry*,  pathology,  physiopathology
Least-Squares Analysis
Linear Models
Male
Podocytes / chemistry*,  ultrastructure*
Proteinuria / etiology,  metabolism,  pathology
Renal Insufficiency / etiology*,  metabolism,  pathology,  physiopathology
Risk Assessment
Risk Factors
Sex Factors
Trihexosylceramides / metabolism*
United States
Up-Regulation
Young Adult
Grant Support
ID/Acronym/Agency:
U54 NS065768/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Trihexosylceramides; 60-27-5/Creatinine; 71965-57-6/globotriaosylceramide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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