On May 23, 2007, the U.S. Food and Drug Administration (FDA) asked manufacturers of all gadolinium-based contrast agents used in magnetic resonance imaging (MRI) to include a black-box warning on the products’ labeling. The warning came after reports of patients developing nephrogenic systemic fibrosis, or NSF.

NSF is a debilitating and potentially fatal disease that inhibits skin and tissues from moving by causing them to thicken. It may also cause organs to thicken, as well. The cause of the disease is unknown, and no consistent treatment exists.

The warnings on the labels would state that patients with severe kidney insufficiency who receive a contrast agent are at risk for developing NSF. It would also state that liver transplant patients or patients with chronic liver disease are also at risk if they experience any degree of kidney insufficiency.

There have been 128 reports of NSF, all of which involve a patient who had severe kidney failure or impairment. No reports of NSF developing in patients with normal kidney function or with mild to moderate kidney insufficiency have been received. Patients with liver problems also have an increased risk of kidney problems.

Gadolinium-based contrast agents are often used to improve visibility of internal structures in patients undergoing an MRI. Gadolinium is a metal with a small magnetic field that can provide a greater contrast between normal and abnormal tissue in the body during an MRI.

The five contrast agents that have been approved for use in the US include:

• Magnevist
• Omniscan
• OptiMARK
• MultiHance
• Prohance

Single and multiple administrations of contrast agents have resulted in the development of NSF, but reports have not consistently been able to identify a specific agent. When agents could be identified, Omniscan was the most commonly reported agent, followed by Magnevist and OptiMARK.

Doctors are advised to screen patients for kidney problems before administering an imaging agent and should allow enough time to elapse to ensure elimination of a dose before administering another. The recommended dose for contrast agents should not be exceeded.

Source: Food and Drug Administration Release P07-90, May 23, 2007; Jennifer Corbett Dooren, “MRI contrast agents draw warning,” Wall Street Journal, May 24, 2007.