title: Synchrotron X-ray analyses demonstrate phosphate-bound  gadolinium in skin in nephrogenic systemic fibrosis.
abstract: 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.
  
  
  OBJECTIVE
  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.affiliation: Department of Applied Science, University of California, Davis, CA 95616, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: George
authors.forename: S M
authors.initials: SM
authors.lastname: Webb
authors.forename: J L
authors.initials: JL
authors.lastname: Abraham
authors.forename: S P
authors.initials: SP
authors.lastname: Cramer
mesh_terms: D001344:Autopsy; D002118:Calcium / Q000032:analysis; D005682:Gadolinium / Q000032:analysis*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D054989:Nephrogenic Fibrosing Dermopathy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010710:Phosphates / Q000032:analysis; D012867:Skin / Q000737:chemistry* / Q000473:pathology; D013050:Spectrometry, Fluorescence / Q000379:methods*; D017356:Synchrotrons
chemical_list: D010710:Phosphates; D005682:Gadolinium; D002118:Calcium