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Review
. 2019 Mar;28(2):154-162.
doi: 10.1097/MNH.0000000000000475.

Gadolinium-based contrast agents: why nephrologists need to be concerned

Katarina Leyba  1 , Brent Wagner  2   3   4
Affiliations
Review

Gadolinium-based contrast agents: why nephrologists need to be concerned

Katarina Leyba et al. Curr Opin Nephrol Hypertens. 2019 Mar.

Abstract

Purpose of review: The hegemony of gadolinium-based contrast agent-induced adverse events stretches beyond those who have renal impairment. 'Nephrogenic' systemic fibrosis is a misnomer: gadolinium-based contrast agents are the known trigger for the disease; kidney impairment is a risk factor. Impaired (true) glomerular filtration may be one catalyst for gadolinium-based contrast agent-induced adverse events, but it is increasingly evident that the same cluster of symptoms occurs in patients with normal renal function.

Recent findings: It has been known for nearly 30 years that gadolinium-based contrast agents distribute and are cleared according to a three compartment model. Single doses of gadolinium-based contrast agents can trigger 'nephrogenic' systemic fibrosis in nondialysis dependent patients. Manifestations have occurred years after exposure. Renal insufficiency alone is not an adequate explanation for 'nephrogenic' systemic fibrosis, and the continuum of its symptoms with the adverse events reported by patients with normal renal function clearly indicate that the physiologic reactions are largely undefined.

Summary: Gadolinium-based contrast agents should be used with extreme caution.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
National estimates for sales of gadolinium-based contrast agents in 2007. The Food and Drug Administration boxed warning cautioning against the use of gadolinium-based contrast agents was on 23 May 2007. Note that this boxed warning remains in the prescribing information for all gadolinium-based contrast agents regardless of chemical structure or valence. The American College of Radiology - based only on retrospective case reports and case series - categorized gadolinium-based contrast agents into three groups: group I, agents with the greatest number of ‘nephrogenic’ systemic fibrosis cases; group II, agents associated with ‘few, if any unconfounded cases’ of ‘nephrogenic’ systemic fibrosis; and group III, ‘agents for which data remains limited regarding (‘nephrogenic’ systemic fibrosis) risk, but for which few, if any unconfounded cases of (‘nephrogenic’ systemic fibrosis) have been reported’. Note that group II agents (MultiHance and ProHance) represented a small market share (9 and 5%, respectively) when ‘nephrogenic’ systemic fibrosis was linked to gadolinium-based contrast agents and none of the group III agents were being used to any significant degree.
FIGURE 2.
FIGURE 2.
The Girardi et al. criteria for the diagnosis of ‘nephrogenic’ systemic fibrosis. ‘Nephrogenic’ is a misnomer because renal insufficiency seems to be a catalyst for the disease, whereas the genesis is certainly gadolinium-based contrast agent exposure [11]. The diagnostic criteria are based on clinical and histopathologic scores [13▪▪]. The degree of renal impairment is not part of the diagnostic criteria. A history of exposure to gadolinium-based contrast agents is not part of the diagnostic criteria. NSF, ‘nephrogenic’ systemic fibrosis.
FIGURE 3.
FIGURE 3.
Market share of gadolinium-based contrast agents (in packages sold) from US manufacturers to nonretail channels of distribution. Adapted from [3▪▪].
See this image and copyright information in PMC

References

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    1. FDA. Gadolinium retention after gadolinium based contrast magnetic resonance imaging in patients with normal renal function. Briefing document. Medical Imaging Drugs Advisory Committee Meeting Washington, DC; 2017. Available from: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/MedicalImagingDrugsAdvisory-Committee/UC.... [Cited Food & Drug Administration] [Accessed 30 June 2018].

      The Food and Drug Administration (FDA) convened a meeting to address the growing concerns among clinicians, radiologists, and patients about long-term retention of gadolinium in numerous tissues regardless of renal function. A theme repeated among industry representatives, FDA officers, and patients was that gadolinium retention in the setting of normal kidney function represented a continuum with ‘nephrogenic’ systemic fibrosis.

    1. Wagner B, Drel V, Gorin Y. Pathophysiology of gadolinium-associated systemic fibrosis. Am J Physiol Renal Physiol 2016; 311:F1–F11. - PMC - PubMed
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