This post is by Christopher M. Kramer MD, FACC, from the Departments of Medicine and Radiology, University of Virginia Health System, in Charlottesville, Va.

*********************************

Gadolinium-based 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).

CGCA 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

[youtuber youtube='http://www.youtube.com/watch?v=kHEzfhh7epI']

*************

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.

< Back to Listings