Gadolinium based contrast agents, and magnetic imaging
Acute kidney failure, and NSF
In 1997 dermatologists first began to see a new disease. They reported symptoms of swelling and tightening of the skin, most frequently on the hands and/or the feet, but sometimes on the back, chest, and abdomen. The skin became reddened or darkened and over time came to feel stiff and woody, its texture like the peel of an orange. The thickened patches were symmetrical, occurring on both right and left sides. The region from ankles to thighs was the most frequently affected, followed by involvement between the wrist and upper arms.
The common factors linking every reported case of NSF were a history of acute kidney failure, and a recent MRI or MRA involving the use of a gadolinium contrast agent.
The syndrome was called Nephrogenic Fibrosing Dermopathy. As more cases were reported, and understanding of the syndrome increased, the name was changed to Nephrogenic Systemic Fibrosis.
Symptoms also included severe itching and deep pain. When the thickening occurred across ankles, knees, wrists and other joints, the tightening skin caused the joint to contract, immobilizing it. Contractures of the joint, especially knees and ankles were often so severe as to be crippling. The disease often progressed so rapidly that within weeks of onset, patients would be immobilized and confined to a wheelchair.
Onset of symptoms occurred 2 days to 18 months after the MRI or MRA. By 2003, accumulating evidence pointed to the use of gadolinium based contrast dyes as a causal agent in the disease.
The FDA's black box warning
The FDA's strongest warning for a drug is a black box warning, also known as a black-box warning, for the thick black line surrounding the warning in the drug's package insert, the informational material that accompanies the drug. In May 2007 the FDA required manufacturers of Gadolinium Based Contrast Agents to include this black box warning:
- Acute or chronic severe renal insufficiency (glomerular filtration rate < 30 mL/min/1.73m2), or
- Acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period.
In these patients, avoid use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle and internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time for elimination of the agent from the body prior to any readministration.
The FDA cautions physicians against using Gadolinium Based Contrast Agents with patients with kidney failure symptoms, and advises that they should be used only when the diagnostic information is essential, and cannot be gained in any other way.