Document Detail


Synchrotron X-ray analyses demonstrate phosphate-bound gadolinium in skin in nephrogenic systemic fibrosis.
MedLine Citation:
PMID:  20560953     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Nephrogenic systemic fibrosis (NSF) is an incurable, debilitating disease found exclusively in patients with decreased kidney function and comprises a fibrosing disorder of the skin and systemic tissues. The disease is associated with exposure to gadolinium (Gd)-based contrast agents (GBCA) used in magnetic resonance imaging (MRI). Tissue samples from many patients with NSF contain micron-sized insoluble Gd-containing deposits. However, the precise composition and chemical nature of these particles is unclear.
OBJECTIVES: To clarify the precise chemical structure of the Gd-containing deposits in NSF tissues.
METHODS: Autopsy skin tissues from a patient with NSF were examined in situ using synchrotron X-ray fluorescence (SXRF) microscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy and in correlation with light microscopy and the results of scanning electron microscopy /energy dispersive spectroscopy analyses.
RESULTS: The insoluble Gd deposits were shown to contain Gd no longer coordinated by GBCA chelator molecules but rather in a sodium calcium phosphate material. SXRF microscopy shows a clear correlation between Gd, Ca and P. EXAFS spectroscopy shows a very different spectrum from the GBCAs, with Gd–P distances at 3·11 A and 3·11 A as well as Gd–Gd distances at an average of 4·05 A, consistent with a GdPO4 structure.
CONCLUSIONS: This is the first direct evidence for the chemical release of Gd from GBCA in human tissue. This supports the physical–chemical, clinical and epidemiological data indicating a link between stability and dose of GBCA to the development of NSF.
Authors:
S J George; S M Webb; J L Abraham; S P Cramer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The British journal of dermatology     Volume:  163     ISSN:  1365-2133     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-03     Completed Date:  2011-01-10     Revised Date:  2011-09-22    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1077-81     Citation Subset:  IM    
Affiliation:
Department of Applied Science, University of California, Davis, CA 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Autopsy
Calcium / analysis
Gadolinium / analysis*
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Nephrogenic Fibrosing Dermopathy / etiology,  metabolism*,  pathology
Phosphates / analysis
Skin / chemistry*,  pathology
Spectrometry, Fluorescence / methods*
Synchrotrons
Grant Support
ID/Acronym/Agency:
EB-001962/EB/NIBIB NIH HHS; GM-65440/GM/NIGMS NIH HHS; R01 EB001962-15/EB/NIBIB NIH HHS; R01 GM065440-08/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Phosphates; 7440-54-2/Gadolinium; 7440-70-2/Calcium

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