This post is by Christopher M. Kramer
MD, FACC, from
the Departments of Medicine and Radiology, University
of Virginia Health System, in Charlottesville, Va.
magnetic resonance contrast agents (GBCA) have been used for well over two
decades and more than 200 million patients have received them safely. In the
early part of the last decade, a dermatologic condition was recognized in
dialysis patients known as nephrogenic systemic fibrosis (NSF), a progressive
induration of the skin that also can involve internal organs and is often fatal
as there is no specific therapy.
Soon thereafter, gadolinium was noted in skin
biopsies of some of these patients and an association between the use of these
agents for MRI and NSF was made. In 2006, the FDA issued a warning in regards
to the use of GBCA in patients with severe chronic kidney disease (CKD). These
agents are cleared by the kidneys with an elimination half-time in patients
with normal renal function of approximately 1.5 hours, but up to 34 hours in
patients with severe CKD (stage 4/5) or acute kidney injury. With prolonged
circulation times, gadolinium can then become unchelated and it is in this form
that it becomes potentially toxic to tissues. The incidence is quite low, with an
estimation of 4.3 cases/1000 patient-years. One review of over 83,000 patients
in the U.S.
identified 15 (0.02%) with NSF and these patients got a higher than standard
dose and many of them had acute renal failure at the time. The disease has not
been identified in patients with milder forms of kidney disease (stage 1-3).
included gadodiamide (Omniscan), gadopentetate dimeglumine (Magnevist),
gadoversetamide (OptiMARK), gadoteridol (ProHance), gadobenate diglumine
(MultiHance), Eovist (gadoxetate disodium) and Ablavar (gadofosveset trisodium).
The first 3 listed above are older agents and have been implicated in more of
the historical cases, in part because of the frequency of their use and in part
because their chelatation of gadolinium is less tight. However, the FDA states
that none of these agents can be considered safe as all have been implicated
with cases of NSF.
Since the FDA
warning in 2006, clinicians have been avoiding the use of these agents in
patients with CrCl<30, using the lowest possible doses for MR studies, and
avoiding repeat studies in these patients. The number of cases of this disease
has fallen to a nearly negligible level. However, on Sept. 9, the FDA required
a change in labeling of all gadolinium-based agents that goes beyond their
previous warning in an attempt to minimize the future risk of NSF. The labeling
will simply suggest that health care professionals should screen patients to
identify those at risk (stage 4/5 CKD or acute kidney injury) and avoid use in
these agents. This change is primarily cosmetic, as the recognition of this
disease and the FDA warning are each more than 4 years old and has already
resulted in changes in practice that have limited the scope of the problem.
UPDATE (9/30): CVN Video
Please note that statements or opinions expressed herein reflect the
views of the contributor, and do not reflect the official views of the
ACCF, unless otherwise noted.