There is an article (Change in Use of Gadolinium-Enhanced Magnetic Resonance Studies in Kidney Disease Patients After US Food and Drug Administration Warnings: A Cross-sectional Study of Veterans Affairs Health Care System Data From 2005-2008 ) and an editorial (Nephrogenic Systemic Fibrosis and Gadolinium-Enhanced Magnetic Resonance Imaging: Does a US Food and Drug Administration Alert Influence Practice Patterns in CKD?) about Nephrogenic Systemic Fibrosis (NSF) in the September issue of the American Journal of Kidney Diseases examining the effect of the FDA’s warning about the use of gadolinium containing contrast agents in patients with compromised renal function.
I’ve written about NSF several times previously. Briefly, it’s a systemic fibrotic disorder that superficially resembles scleroderma. It was first recognized in 1997 and linked to gadolinium containing contrast agents that are commonly used in magnetic resonance imaging (MRI) in 2006. Gadolinium appeared to trigger the disorder in patients with advanced renal failure, ie those with glomerular filtration rates <30 ml/min. The current study from the Veterans Administration showed, not surprisingly, that since the FDA warned about the association with gadolinium and NSF that the number of gadolinium enhanced MRI studies had markedly decreased.
The editorial by Diego Martin, a radiologist at Emory, gives several reasons why the decline may not serve the best interests of patients in need of diagnostic imaging studies. When the FDA issued its black box warning about gadolinium it applied to all five of gadolinium-based contrast agents available in the US though all five appear to differ in the propensity to cause NSF. In fact, most of the cases of NSF were associated with gadodiamide (Omniscan). This preparation is the least stable of the five; stability , or rather the lack of it, has been thought to be of great importance in the development of NSF. Recent reports indicate that the incidence of NSF appears to be zero, even in patients with severely diminished renal function, following the use of higher stability gadolinium contrast agents, specifically gadobenate dimeglumine.
Thus the first problem is that the FDA has not distinguished between those gadolinium preparations that may cause NSF from those that may pose no risk at all. This has likely caused many clinicians to not order gadolinium enhanced MRIs in patients in whom there is not risk of NSF. This reluctance may have spread to patients whose GFRs are greater than 30 ml/min. Patients may be getting CT scans instead of MRIs because of the fear of NSF. CTs carry their own risks. Ionizing radiation is carcinogenic. Iodinated contrast agents have their own range of toxicity. Also, MRIs in some patients may yield better diagnostic information than that obtained with a CT.
The FDA, as is true of most organizations both in and out of the government, wants to do good. It’s just that wanting to do good and actually doing it are different. The former is much easier than the latter; intention and outcome are often conflated. The solution of this problem is for the various clinical groups interested in the problem of gadolinium and NSF to examine all the data and to continually refine recommendations that will best serve patient care. It seems that the current black box advisory on all gadolinium preparations should be re-examined and changed appropriately.
