Gadolinium Side Effects

Gadolinium side effects have recently been linked to patients undergoing magnetic resonance imaging (MRI). Gadolinium for MRI is used to improve the visibility of internal organs and tissue so the radiologist can more easily detect abnormalities. A population-based study led by Dr. Aneet Deo revealed that patients with end stage renal disease (ESRD) were at an increased risk for gadolinium side effects. Nephrogenic systemic fibrosis (NSF) was found in ESRD patients after gadolinium exposure.

The study analyzed data from 467 patients on kidney dialysis due to ESRD. MRI with gadolinium was reported in 87 patients who underwent 123 radiological studies, the most common being MRI of the abdomen and pelvis. The study was the first to strongly associate gadolinium side effects like NSF with dialysis patients. The researchers documented 4.3 cases of NSF per 1000 patient-years. From these initial studies it appears that only patients with end stage renal disease (kidney disease) seem to be at risk of developing the debilitating skin disorder nephrogenic systemic fibrosis (NSF).

Nephrogenic systemic fibrosis is a systemic disorder that is potentially fatal. NSF is characterized by thickening and tightening of the skin. It was first observed in 1997 when it was referred to as nephrogenic fibrosing dermopathy (NFD). Although the exact cause of NSF is unknown, recent studies have shown a link between NSF and patients with kidney problems following gadolinium MRI exposure.

The gadolinium side effect NSF usually starts in the lower extremities although it can also develop in the diaphragm, muscles in the thigh and lower abdomen, and lungs. As patients develop skin thickening they can suffer from decreased joint mobility resulting from the inability to bend and extend joints. NSF has been reported following administration of all five of the FDA approved gadolinium contrast agents: Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance.

In response to the association of NSF and gadolinium MRI the Food and Drug Administration (FDA) has issued a healthcare alert including new warnings regarding nephrogenic systemic fibrosis.
The FDA's new boxed warning is for patients at risk for the gadolinium side effect NSF.

The boxed warning includes the following warnings and recommendations:

• Exposure to gadolinium-based contrast agents (GBCA) increases the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency, or acute renal insufficiency due to the hepato-renal syndrome or in the perioperative liver transplantation period.

• NSF is a debilitating and sometimes fatal disease affecting the skin, muscle, and internal organs.

• Avoid use of gadolinium unless the diagnostic information is essential and regular MRI studies are not available.

• All patients should be screened for renal dysfunction (kidney problems) by obtaining a history and if necessary laboratory test.

• When administering a gadolinium contrast agent, do not exceed the recommended dose outlined in the product labeling. Prior to any readministration of gadolinium there needs to be sufficient time for elimination of the gadolinium.

The FDA is currently considering other risk management options in response to the discovery of gadolinium side effects in patients after undergoing MRI studies. Patients are strongly urged to contact their doctor immediately after receiving a gadolinium MRI if they have any of the following symptoms that may indicate the development of NSF:

Skin and eyes

• Swelling, hardening and tightening of your skin
• Reddened or darkened patches on the skin
• Burning or itching of your skin
• Yellow raised spots on the whites of your eyes

Bones and muscles

• Stiffness in your joints; problems moving or straightening arms, hands, legs, or feet
• Pain deep in your hip bones or ribs
• Muscles weakness

The reported time between a patient undergoing an MRI with gadolinium and diagnosis of NSF varies widely among patients. It can range from days to several months. Patients suffering from NSF can die from complications related to the disease.