Gadolinium MRI Contrast Agent Injury

Gadolinium based MRI contrast agents increase risk of Nephrogenic Systemic Fibrosis (NSF) and Nephrogenic Fibrosing Dermopathy (NFD) when administered to patients with renal insufficiency.

MRI (magnetic resonance imaging) and MRA (magnetic resonance angiography) are non-invasive medical tests that allow physicians to see images of the living tissues within the human body.  They are a critical part of the diagnosis and treatment processes because they provide detailed images of organs, soft tissues, bone, arteries and blood vessels and virtually all internal body structures. 

Contrast agents or dyes are used to enhance images on MRI to allow for improved visibility of internal structures and allow for better delineation between normal and abnormal tissues.  Although iodine based contrast agents have been used for many years, they have been linked to acute renal failure.  In 1999, gadolinium contrast agents were approved for use in MRI.  However, the gadolinium-based agents have now been linked to a debilitating and potentially life-threatening condition for patients with severe kidney insufficiency. 

The FDA issued a news release on May 23, 2007 requesting that manufacturers of the gadolinium based contrast agents include a new black box warning on the product labeling of these agents stating that patients with renal insufficiency who receive gadolinium-based agents “are at risk for developing a debilitating, and a potentially fatal disease known as nephrogenic systemic fibrosis (NSF)” or nephrogenic fibrosing dermopathy (NFD).  It also states that liver transplant recipients, individuals with chronic liver disease are also at risk for developing NSF / NFD if they are experiencing kidney insufficiency in addition to their liver condition.

Gadolinium Based MRI Contrast Agents

There are five gadolinium based contrast agents currently approved for use in the U.S.  They are Magnevist (gadopentetate dimeglumine), Ominiscan (gadodiamide), OptiMARK (gadoversetamide), MultiHance (gadobenate dimeglumine), and Prohance (gadoteridol).  Because of incomplete data, it is not possible to know if the extent of risk for developing NSF is the same for all agents.  Therefore, patients should be screened for kidney problems prior to undergoing MRI with one of these imaging agents.  Although NSF has been identified following both single and multiple administrations of gadolinium based agents, it has specifically been identified following sequential administration of Omniscan and MultiHance and Omniscan and ProHance.

Signs of Injury or Illness

In a healthy individual, gadolinium is removed from the body by the kidneys.  When the kidney functioning is compromised, the gadolinium remains in the body causing serious harm.  NSF / NFD can take weeks or months to appear in patients but once it begins the disease develops and progresses rapidly and can be fatal.  If you have undergone MRI or MRA and are experiencing any symptoms which may be related to NSF / NFD, you should seek immediate medical attention. 

Symptoms of NSF / NFD include:

• Burning, itching or swelling
• Hardening or tightening of the skin, generally in the extremities
• Variations in skin texture, similar to an orange peel
• Red or dark patches on the skin
• Yellow spots in the whites of the eyes
• Muscle weakness
• Deep skeletal pain, especially in the hips and ribs
• Joint stiffness and difficulty straightening limbs and extremities

Injured by Gadolinium based Contrast Agent?

If you or a family member have undergone MRI / MRA screening with contrast in the recent past and are experiencing any of the above symptoms, you should contact your healthcare provider immediately.  This life-threatening condition progresses rapidly and can be fatal.

You may be entitled to compensation from those responsible for the injury.  At Arnold & Itkin LLP, our attorneys have the knowledge and experience to take on large medical product manufacturers and hold them accountable for their actions.

Gadolinium MRI Contrast Agent Questions & Answers

(Source: FDA.gov)

What is gadolinium and what is its use in clinical medicine?

Gadolinium is a paramagnetic metal ion. Paramagnetic ions, such as gadolinium, tend to move into magnetic fields. This trait makes paramagnetic ions such as gadolinium useful for MRI and MRA.

Gadolinium-based contrast agents are manufactured by a chelating process, a procedure in which large organic molecules form a stable complex around the gadolinium. The chelate reduces the chances of toxicity that could result from exposure to free gadolinium. This stable complex is eliminated via the kidneys in patients with normal functioning kidneys.

Gadolinium-based contrast agents are approved by FDA for use with MRI as a contrast agent to provide an improved image of body organs and tissues.

Gadolinium-based contrast agents are also used for MRA, another imaging procedure used to evaluate blood vessels.

What is the difference between MRA and MRI?

MRA is a special type of MRI used to study blood vessels. MRA is utilized to aid in the detection of heart disorders, stroke, and vascular diseases.

Can an MRI and MRA be performed without gadolinium-based contrast?

Yes, MRI and MRA can be performed without contrast.

MRI with gadolinium-based contrast agents provides additional diagnostic information as compared to MRI without contrast.

The use of gadolinium-based contrast agents in MRA is not FDA approved. MRA with gadolinium-based contrast is thought by many radiologists to provide more detailed images of blood vessels than MRA without gadolinium-based contrast.

Are there other approved MRI contrast agents that do not contain gadolinium?

Yes. However, the two other approved MRI contrast agents, Feridex, I.V. (an iron-containing injectable solution) and Teslascan (a manganese-containing injectable solution) are FDA-approved only for the evaluation of lesions of the liver. Imaging contrast agents, such as iodinated contrast agents are used in Computed Tomography, plain X-ray and X-ray angiography. However, these iodinated contrast agents require X-ray imaging rather than MRI.

What is the concern regarding gadolinium-based contrast agents?

Patients with moderate (glomerular filtration rate less than 60 mL/min/1.73m2) to end-stage (glomerular filtration rate less than 15 mL/min/1.73m2 or on dialysis) kidney disease who receive gadolinium-based contrast agents are at risk for developing a serious systemic fibrosing disease called Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD).

As of December 21, 2006, FDA has received 90 reports of NSF/NFD in patients who received gadolinium-based contrast agents for MRI and MRA. In addition, researchers have found gadolinium deposits in the skin of patients with NSF/NFD. The association between NSF/NFD was first reported in a May 29, 2006, press release from the Danish Medicines Agency (DMA) and the April 2006 report by Grobner et al in Nephrology, Dialysis and Transplantation (2006) Vol 21 (4):1104-1108 and following erratum (2006) 21(6): 1745.

What is Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD)?

NSF/NFD was first described in the medical literature in 2000. The first case of NSF/NFD was identified in 1997. The disease is observed in patients that have moderate to end-stage kidney disease. NSF/NFD causes fibrosis of the skin and connective tissues throughout the body. Patients develop skin thickening that may prevent bending and extending joints, resulting in decreased mobility of joints. NSF/NFD usually starts in the lower extremities. Fibrosis can also develop in the diaphragm, muscles in the thigh and lower abdomen, and lung vessels. The clinical course of NSF/NFD is progressive and may be fatal.

What is the treatment for NSF/NFD?

There is no known treatment for NSF/NFD.

Improved renal function (spontaneous or via renal transplantation) appears to slow or arrest NSF/NFD and may even result in a gradual reversal of NSF/NFD. Other treatments are being tested.

How many gadolinium-based contrast agents has FDA approved? Was NSF/NFD seen with all of the U.S.-approved gadolinium-based contrast agents?

There are five FDA approved gadolinium-based contrast agents (Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance).

Of the 90 cases of NSF/NFD FDA has received, most have been associated with the administration of Omniscan. Other cases, however, have been associated with Magnevist and OptiMARK exposure. Although NSF/NFD has been reported for only 3 of the 5 gadolinium-based contrast agents, FDA believes that NSF/NFD may occur with the use of any of the approved gadolinium-based contrast agents.

Do the gadolinium-based contrast agents cause NSF/NFD?

Whether the gadolinium-based contrast agents are the only agents or conditions that may be associated with NSF/NFD in patients with renal disease is unknown. However, the 90 case reports FDA has received and the finding of gadolinium deposits in the skin of patients with NSF/NFD suggests that gadolinium-based contrast is a factor in the development of NSF/NFD in patients with moderate to end-stage kidney disease.

What actions will FDA take regarding the new information about gadolinium-based contrast agent administration and the development of NSF/NFD in patients with moderate to severe kidney disease?

FDA is continuing to evaluate the 90 case reports, is having ongoing discussions with NSF/NFD experts, is reviewing results of clinical trials with gadolinium-based contrast agents, and is working with the manufacturers to review all safety reports and adverse event reports. FDA will be initiating labeling changes for gadolinium-based contrast agents.

What information was known about serious side effects prior to the approval of gadolinium-based contrast agents?

The five U.S. approved gadolinium-based contrast agents were approved between 1988 and 2004. In the combined pre-marketing studies for these approved gadolinium-based contrast agents, over 3000 patients were studied.

The most common serious side effect from gadolinium-based contrast agents is an allergic reaction that is usually mild but is occasionally severe and even results in fatalities. Some patients develop skin conditions, such as rash, sweating, itching, hives, and facial swelling. Most of these conditions are allergic in nature.

Gadolinium-based contrast agents can be very irritating to the veins into which they are injected, causing irritation of blood vessels and skin and the formation of blood clots.

Very few patients with severely compromised kidney function or those on dialysis have been studied in clinical trials. The labels for gadolinium-based contrast agents caution that the risk of toxic reactions may be greater in patients with impaired kidney function because gadolinium is mostly excreted by the kidney.

More information about Gadolinium-based MRI Contrast Agents

FDA Requests Boxed Warning for Contrast Agents Used to Improve MRI Images

FDA.gov – May 23, 2007

 

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