Nephrogenic Systemic Fibrosis or Nephrogenic Fibrosing Dermopathy (NSF/NFD) is a disease that may occur in people with moderate to end-stage kidney disease (ESRD) after undergoing a Magnetic Resonance Imaging (MRI) or Magnetic Resonance Angiography (MRA) scan with a gadolinium-based contrast agent.
An MRI scan creates detailed images of internal body structures through the use of radio waves, magnetism, and a computer. An MRA scan obtains images that show the structure of blood vessels. Sometimes a contrast agent, or a substance with specific magnetic properties, is introduced to delineate particular areas of interest on the images these scans produce.
Gadolinium is a contrast agent that looks like water and is non-radioactive. After being injected intravenously, it accumulates in abnormal tissue, causing it to brighten significantly on images produced by MRI and MRA scans. It is also known as gadodiamide and gadolinium-DPTA and goes by various brand names, including Magnevist (made by Berlex Laboratories, Inc.), Omniscan (made by Nycomed Amersham PLC), ProHance and MultiHance (made by Bracco Diagnostics, Inc.), and OptiMARK (made by Mallinckrodt).
By producing gadolinium contrast agents through a chelating process, the gadolinium becomes more stable and less likely to be toxic, allowing patients with normal functioning kidneys to excrete it after it is introduced into their bodies.
Gadolinium is the only contrast agent approved by the FDA for use with MRI scans (not MRA scans), but several reports of patients who developed NSF/NFD after undergoing MRI and MRA scans with a gadolinium-based contrast agent prompted the FDA to warn patients and healthcare providers
that “patients with moderate to end-stage kidney disease who receive an MRI or MRA with a gadolinium-based contrast agent may get NSF/NFD which is debilitating and may cause death.”
NSF/NFD is a progressive disease that occurs in patients with noticeably advanced renal failure. It was first seen in 1997 and causes fibrosis of the skin and connective tissues throughout the body. It begins with darkened or reddened patches, plaques, or papules. Patients then develop skin thickening that limits their mobility.
In some patients, the fibrosis spreads and/or they may experience itching, burning, or sharp pains in the lower abdomen, the diaphragm, muscles in the lower thigh. It may also spread to the interior areas of lung vessels and elsewhere. Additional symptoms may include muscle weakness, deep “bone pain” in the hips and ribs, difficulty breathing, severe illness and death. About 5% of patients have a rapidly progressive course.
Although there is currently no consistently effective treatment for NSF/NFD, improving renal function appears to slow or arrest it, and may even reverse it.
The FDA has not definitively concluded that there is a causal relationshipbetween gadolinium-containing contrast agents and the development of NSF/NFD because the evidence is from case reports of patients with concurrent medical illness or use of other medications that could also be contributing to the development of the condition. There is research, however, which indicates that gadodiamide is attributable to approximately 90 to 95 percent of all reported cases of NSF/NFD.
The FDA is continuing to evaluate available information and holding discussions with experts. It is considering modifying product labeling, requiring additional studies, and implementing risk management procedures. Meanwhile, patients with impaired kidney function who have been administered a gadolinium-containing contrast are urged to alert their physician. Physicians should consider a prompt dialysis and report the case to the FDA’s MedWatch athttp://www.fda.gov/medwatch/.