Revisiting the risks of MRI with Gadolinium based contrast agents—review of literature and guidelines
Revisiting the risks of MRI with Gadolinium based contrast agents-review of literature and guidelines
Aurang Z. Khawaja 0 1 2 3
Deirdre B. Cassidy 0 1 2 3
Julien Al Shakarchi 0 1 2 3
Damian G. McGrogan 0 1 2 3
Nicholas G. Inston 0 1 2 3
Robert G. Jones 0 1 2 3
0 Present address: Division of Diabetes and Cardiovascular Medicine, University of Dundee , Dundee DD19SY , UK
1 Department of Renal Transplant Surgery & Vascular Access, Queen Elizabeth Hospital, University Hospitals Birmingham , Mindelsohn Way, Birmingham B15 2GW, West Midlands , UK
2 Aurang Z. Khawaja
3 Department of Radiology, Queen Elizabeth Hospital, University Hospitals Birmingham , Mindelsohn Way, Birmingham B15 2GW, West Midlands , UK
Gadolinium based contrast agents (GBCA) have been linked to the occurrence of nephrogenic systemic fibrosis (NSF) in renal impaired patients. The exact interaction between the various different available formulations and occurrence of NSF is not completely understood, but has been postulated. This association has triggered public health advisory bodies to issue guidelines and best practice recommendations on its use. As a result, the reported incidence of NSF, as well as the published use of GBCA-enhanced magnetic resonance imaging in renal impairment, has seen a decline. Understanding of the events that led to these recommendations can increase clinical awareness and the implications of their usage. We present a review of published literature and a brief overview of practice recommendations, guidelines and manuals on contrast safety to aide everyday imaging practice. Teaching Points Low risk gadolinium based contrast agents should be the choice in renal insufficiency. Higher doses have been linked to NSF development. Doses should be as low as possible. Clear documentation of date, dose and type of formulation used should be noted.
Magnetic resonance imaging; Contrast media; Gadolinium/adverse effects; Nephrogenic fibrosing dermopathy; Renal insufficiency
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Gadolinium-based contrast agents (GBCA) have been linked
to the occurrence of nephrogenic systemic fibrosis (NSF) in
renal impaired patients. The majority of studies that report on
their use in the renal impaired population were published prior
to the publications that prompted the alert on NSF [1–3]. This
association has triggered public health advisory bodies to
issue guidelines and best practice recommendations on its use in
renal insufficiency. Since then, this has all but halted the rapid
progression and uptake of contrast-enhanced magnetic
resonance imaging (MRI) in this population that was seen in the
early to mid 2000s. Understanding of the events that led to
these recommendations can increase clinical awareness and
the implications of the use of GBCAs in daily imaging
practice. We conducted an electronic database search [PubMed/
Medline, EMBASE] to collate the evidence in published
literature on the occurance of NSF in the renal impaired. We also
carried out a forward citation and bibliographic search of
identified studies. Published studies were reviewed for reported
pathophysiological and clinical manifestations, proposed
diagnostic pathway, treatments options and reported incidence.
We also reviewed practice recommendations, guidelines and
published manuals on contrast safety.
Background and incidence In the year 2000, 15 patients with
chronic kidney disease were identified presenting with
scleromyxoedema-like cutaneous manifestations yet having
significant clinical and histo-pathological differences; the term
nephrogenic fibrosing dermopathy was initially proposed.
These clinical findings are now recognized as characteristic
of NSF [4]. Following this, case reports of similar findings and
also significant systemic involvement found on autopsy were
reported [5, 6]. Patients with end-stage renal disease were
reported to develop symptoms as early as two to four weeks
after exposure to GBCAs for MRI [1]. Exact pathogenesis
remains unclear; however, postulation of likely early dermal
manifestation of this gadolinium toxicity is proposed [7]. A
strong association is observed in the presence of both acute
renal impairment and chronic dialysis dependent renal
insufficiency and other influencing co-factors that may play a role,
such as a background inflammatory process [8, 9]. As the
evidence in published literature increased, the United States
Food and Drug Administration (FDA), followed by the
European Medicines Agency (EMA) issued an alert on the use of
GBCAs in patients with renal insufficiency [10, 11]. Since
then, public health and practice guideline bodies have
published recommendations on its use [12–14]. A 2008
multicentre retrospective review reported 15 cases of NSF in a total
population of 83,121 (0.02 % incidence), all of whom
received at least one administration of a GBCA. All 15 of these
cases of NSF were found in patients who had received a
higher than standard dose, increasing the incidence to
0.17 % (15 of 8997 patients). A hig (...truncated)