Products Liability Newsletter
Gadolinium-Based Contrast Dyes and Nephrogenic System Fibrosis
What Gadolinium is and How it is Used
Gadolinium is a metallic element found in the earth’s crust; it is a paramagnetic metal ion. This means it moves differently from other particles in a magnetic field. That makes it useful in magnetic resonance imaging procedures (MRIs) because it can be made into contrast agents that, when injected into the body, help make internal structures more visible during the MRI. Thus, gadolinium can be used to help find abnormal growths and tumors in organs. Because Gadolinium is a dangerously toxic material in its natural free state, it goes through a chelating process. In this procedure, a large organic molecule surrounds the gadolinium molecule to form a stable complex, which reduces the chance of toxicity from being injected with a gadolinium-based contrast agent (GBCA). The kidneys predominantly eliminate this stable complex; people with healthy kidneys typically excrete the compounds and all of the gadolinium within a couple of hours.
The Food and Drug Administration (FDA) approved five GBCAs for use in MRIs between 1998 and 2004. The five approved GBCAs are marketed under the names Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance. Some doctors also use GBCAs in magnetic resonance angiography (MRA) procedures, which are used to evaluate blood vessels, but the FDA has not approved it for this use. Although the FDA has approved two other contrast agents that do not contain gadolinium, they are only approved for use in the liver.
Dangers of Gadolinium-based Contrast Agents and Nephrogenic System Fibrosis
Although most patients injected with GBCAs appear to experience no or very minor adverse affects, certain patients develop severe, potential fatal side affects. Patients with normal kidney functions are able to quickly excrete the gadolinium through their kidneys, but patients with poor or insufficient kidney function have been linked to an untreatable condition called Nephrogenic System Fibrosis (NSF), also known as Nephrogenic Fibrosing Dermopathy (NFD). The first known case of NSF was discovered in 1997. Before the FDA approved the GBCAs for use, studies were done on about 3,000 patients. However, very few of the patients in these pre-market studies suffered from severe kidney disease, and thus the potential NSF risk for those patients was undiscovered.
NSF is a severe, debilitating, and currently incurable disorder that causes fibrosis, or an increased formation of connective tissue in the skin. This causes the skin to harden and become coarse, which may prevent bending and extending joints and may leave some unable to walk. NSF usually starts developing in the lower limbs but can also affect the diaphragm, torso, lungs, and eyes. It gets worse over time and can ultimately cause severe disability or even death. Improved kidney function, either by the kidney healing itself or through a transplant, can help slow or stop NSF development and even gradually reverse it, but there is no other known treatment. Cases of NSF have been tied to the administration of all five of the approved GBCAs, and the FDA warns patients of the following symptoms:
- Reddened or darkened patches of skin
- Swelling, hardening, or tightening of the skin
- Burning or itching of the skin
- Yellow raised spots on the whites of eyes
- Joint stiffening or difficulty extending or bending arms, legs, hands, or feet
- Muscle weakness
- Pain deep in the hip joints or ribs
The FDA has not yet been able to determine whether the gadolinium in the gadolinium-based contrast agents is the only cause of NSF in patients with kidney disease. However, the FDA admits that several published medical reports suggest that patients who have developed NSF have gadolinium deposits in their skin caused by the administration of GBCAs. NSF appears in both male and female patients and patients of all ages, races, and from a variety of nationalities.
Other conditions linked to NSF include coagulation abnormalities, deep venous thrombosis (DVT), and recent vascular surgery. Commonly, an NSF patient has recently undergone a vascular surgical procedure or has experienced a thrombotic episode approximately two weeks before the onset of the skin changes signaling NSF development.
FDA Response to NSF Caused by Gadolinium-based Contrast Agents
In response to the NSF cases caused by GBCAs, the FDA requested that the manufacturers of the five approved GBCAs add new warnings to the products’ boxes and in the warning labels. The FDA requested that these new warnings discuss the risks of patients with severe kidney disease developing NSF after using this product.
The FDA also asked the manufacturers to collect data about patients with varying degrees of poor kidney function who have been exposed to GBCAs, so that they can more accurately estimate the risk of NSF for patients with kidney disease. The FDA has vowed to keep monitoring the situation and suggested it might request additional label changes and studies in the future once they learn new information about NSF and its relation to GBCAs.
Not surprisingly, these cases of NSF have resulted in many lawsuits around the country. On February 27, 2008 the United States Judicial Panel on Multidistrict Litigation ordered that the dozens of cases across 13 different federal districts be consolidated in one action in the Northern District of Ohio because the actions all shared common questions of fact. The consolidated case, now called In re: Gadolinium Based Contrast Agents Products Liability Litigation, is still ongoing under Judge Dan A. Polster.
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