The connection between gadolinium and the disease known as nephrogenic fibrosis syndrome (NFS) presents an urgent and immediate reason for imaging centers to amend MR policies, procedures, and protocols.
A flurry of advisories from the FDA, the ACR’s Document for Safe MR Practices: 2007, reports in the peer-review literature, and aggressive activities on the part of the legal community, have put this troubling development front and center for all parties associated with medical imaging.
“To the best of my knowledge yes, imaging center cases have been reported,” says Emanual Kanal, MD, Director, MR Services, University of Pittsburgh Medical Center “I don’t think all of these patients are inpatients at all.”
NSF/NFD, first observed in 1997, causes thickening and hardening of the skin, usually in the extremities, and occurs in patients with underlying renal disease. It is a progressive, irreversible, and potentially fatal disease. Nearly all known cases of the disease have occurred in patients with at least one known exposure to gadolinium within a few days to months prior to developing the disease. But experts still do not know why some patients develop NSF, or how to prevent NSF from occurring.
Nonetheless, the first lawsuit pertaining to NSF and gadolinium was filed in Cleveland by law firm Spagenberg, Shibley & Liber [ http://www.spanglaw.com/] on behalf of a retired Cleveland restaurant supplier who claims he contracted NSF from an MRI contrast agent. Other law firms are actively soliciting NSF patients.
Most experts agree that there is a link, but it is not known whether the causative agent is released free gadolinium, prolonged exposure to abnormally high doses of gadolinium-plus-chelate, the chelate itself or some combination of the above with additional factors related to the biochemistry of patients with severe renal failure, according to the ACR’s Document for Safe MR Practices: 2007. The same document notes that some data suggest that elevated levels of phosphate, iron, zinc, or copper, or the presence of Fosrenol might serve as competitors for the chelate molecule and increase the concentration of free gadolinium in the patient.
Compounding the problem is the fact that a history of multiple prior administrations of gadolinium also appears to be associated with an increased incidence of the development of NSF. And the patients most likely to require high dose administration of gadolinium are the very patients most at risk for developing NSF, namely those with underlying renal disease.
“We are predominantly seeing this in high-dose, such as double- or triple-dose applications” reports Kanal. “It seems that the number one clinical situation for which high dose gadolinium based MR contrast agents are given is an MR angiographic study.”
Because contrast is not typically used in MRA of the brain and a standard dose is typically used in MRA of the carotid arteries, Kanal explains, the patients getting high-dose gadolinium are primarily those who need a non-neurological, body application MR angiogram, such as a peripheral run-off or a cardiac MR examination or MR angiographic evaluation of renal artery stenosis. “So when you stop and think about it, who are the patients that are getting double dose contrast?” asks Kanal. “It’s people who have peripheral artery disease, and patients with renal artery stenosis, and diabetics, and hypertensive patients; in general, frequently it is patients who are likely to have problems with their kidneys. I believe that this is why we are seeing such a predominance of these cases in instances of MR angiography in renal disease patients.”
Kanal adds that known renal disease is a predominant indication to send patients for an MR angiogram rather than to CT, as clinicians and radiologists believe that this might protect these patients from developing contrast-induced nephropathy related to iodinated contrast agents. “And it seems that the worse the renal disease and the higher the dose, the better the chance of developing NSF,” he notes.
Are All Agents Dangerous?
Cases of NFS have been associated with three of the five agents currently approved by the FDA: OmniscanTM, Optimark®, and, Magnevist®. “To go by pure numbers in the peer review literature, to date there have been roughly 55 cases reported to have been associated with a prior Omniscan administration, two reported with a prior Magnevist administration, and none that reported a prior administration