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Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis

https://doi.org/10.1016/j.jaad.2006.10.047Get rights and content

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.

Section snippets

Methods

Thirteen blocks of paraffin-embedded tissue from 7 patients with a clinical and histopathologic diagnosis of NSF were obtained from the NSF Registry. Included with this submission was an additional paraffin-embedded block containing tissue from routine dermatopathology case processed and stored at the same dermatopathology facility. Participants in Colorado were blinded as to which blocks of tissue represented cases of NSF and which blocks represented negative controls. Positive

Control specimens

Large amounts of gadolinium were detected on carbon planchettes coated directly with contrast agent. This provided reassurance that the EDS apparatus could reliably detect gadolinium. Waste tissue doped with gadolinium-containing contrast also contained large amounts of detectable gadolinium upon examination with EDS, indicating that the material survived tissue processing. The needle track from the doping process was readily identified at low magnification, with a decreasing gradient of

Discussion

The cause of NSF has never been convincingly established.8 Admittedly, our study does not establish causation with respect to gadolinium-containing contrast agents used in MRI. Yet this interesting and novel observation of gadolinium particles within the tissue of NSF patients corroborates recent observations of an epidemiologic association between exposure to gadolinium-based contrast agents and development of NSF.9, 10

Accumulation of gadolinium within body tissue from gadolinium-containing

Conclusion

In conclusion, our study provides spectroscopic and histologic evidence to support recent epidemiologic associations between gadolinium-containing contrast and the development of NSF. This pilot investigation documented gadolinium deposition in 4 of 13 specimens from 7 patients with NSF. No gadolinium was detected in a single negative control from a patient without NSF. Correlation is not equivalent to causation, but the presence of gadolinium may implicate certain contrast agents, or even the

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Funding sources: None.

Conflicts of interest: None identified.

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