Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis
Accepted 24 October 2006. published online 13 November 2006.
Background
Nephrogenic systemic fibrosis (NSF) is a disease of unknown etiology that affects a subset of patients with renal insufficiency. Recent publications suggested an association between exposure to gadolinium-containing contrast agents and subsequent development of NSF. We sought to detect gadolinium within the skin and soft tissue of patients with NSF who were exposed to gadolinium-based contrast.
Methods
Paraffin-embedded skin and soft tissue from NSF patients exposed to gadolinium, and from negative controls, was provided by the NSF Registry (New Haven, Conn). The tissue was searched for metals using a field emission scanning electron microscope that was equipped with energy dispersive spectroscopy. The presence of gadolinium and other metals was verified through identification of unique and requisite X-ray emission spectra.
Results
Gadolinium was detected in 4 of 13 tissue specimens from 7 patients with documented NSF who were exposed to gadolinium-based radiographic contrast. No gadolinium was detected in a paraffin-embedded specimen from a negative control. Based upon the known exposure history of patients with detectable gadolinium, a tissue residence time of 4 to 11 months was observed.
Limitations
As this was a pilot investigation, only a single control specimen and a single histological section from each block of tissue were utilized.
Conclusion
In this pilot investigation, gadolinium was detected in the tissue of a number of patients with NSF. Although neither dispositive of a pathophysiologic mechanism, nor proof of causation, the detection of gadolinium within tissue of NSF patients is supportive of an epidemiologic association between exposure to gadolinium-containing contrast material and development of disease.
Denver and Golden, Colorado, and New Haven, Connecticut
dResearch Associate, Materials Sciences and Geochemistry, Colorado School of Mines, Golden
eAssistant Professor, Dermatology & Pathology, Director, International Center for Nephrogenic Fibrosing Dermopathy Research (ICNFDR), Yale University Medical Center
Correspondence to: Whitney A. High, MD, MEng, Department of Dermatology, University of Colorado, Anschutz Cancer Center, 1665 N Ursula, Denver, CO 80010.