Contrast Caution

Physicians who schedule magnetic resonance imaging (MRI) studies for their patients often specify the use of a gadolinium-based contrast agent – a chemical solution injected into the bloodstream that makes for better quality images.

Gadolinium is a rare earth metal that aligns with an MRI’s powerful magnetic field, but it is also toxic, so in its injectable form the metal is bound to chelating molecules to block its dangerous effects. Most of these molecules are then filtered through the kidneys and eliminated.

But there is growing evidence that tiny particles of gadolinium remain in the body – including the brain – causing serious side effects in some people, says kidney researcher Brent Wagner, MD, an associate professor in The University of New Mexico Department of Internal Medicine.

“We’ve come to the conclusion if a living organism gets this stuff there’s a chance that these weird particles can form, and my suspicion is this is what triggers this reaction,” says Wagner, who also serves as a staff physician at the Raymond G. Murphy Veterans Affairs Medical Center in Albuquerque. “It’s probably distributing everywhere in the body once someone gets it.”

Reports first started emerging about 15 years ago that some patients who had received the gadolinium contrast agent were experiencing a painful, debilitating skin condition called systemic fibrosis, which causes skin thickening and tightening in the joints and extremities, as well as internal organ damage.

At first, it was assumed that the reaction only occurred in patients with pre-existing kidney disease, but it later became clear that it also occurs in people with healthy kidneys, Wagner says.

“The kidneys themselves are not the problem,” he says. “There is long-term retention of gadolinium – a known toxic metal – regardless of the brand and irrespective of kidney function. There are thousands of members of social media groups focused on the chronic adverse effects of gadolinium-based contrast agents.”

Now, Wagner leads a team of researchers exploring how gadolinium triggers the systemic reaction in some patients.

It has been theorized that the majority of the skin thickening was due to circulating, bone marrow-derived white blood cells called fibrocytes, Wagner says, adding that the gadolinium appears to produce an inflammatory response that triggers the buildup of fibrocytes in skin tissue.

“My laboratory was the first to prove this experimentally,” he says. “Furthermore, we were the first to demonstrate that bone marrow possesses a ‘memory’ of gadolinium exposure – gadolinium-induced fibrosis is enhanced in those who have had a prior administration of magnetic resonance imaging contrast.”

Much of Wagner’s research to date has been conducted in animal models or using donated tissue. Now, he is recruiting patients for a pilot study in humans through the UNM Clinical & Translational Science Center in hopes of identifying potential treatments.

While many participants have had just one dose of the contrast agent, gadolinium is still detectable in their blood, urine, fingernails and scalp hair without causing symptoms. Wagner stresses that “most people just tolerate it very, very well. If we know why that it is, maybe we have a shot at helping the people who do have symptoms.”

While gadolinium-based contrast agents often play an important role in helping physicians diagnose disease, Wagner believes they should be used with caution and consideration of whether the risks outweigh the potential benefits.

“I don’t know if there’s a true gadolinium deposition disease or not, but I do want to take the patient’s perspective,” he says. “It’s an alien heavy metal that stays in your body.”