Gadolinium MRI Contrast Agents and Nephrogenic Systemic Fibrosis
Nephrogenic Systemic Fibrosis, or NSF, is a fibrosing disorder which results in increased tissue deposition of collagen, often resulting in thickening and tightening of the skin and fibrosis that may involve other parts of the body, including the diaphragm, heart, lungs, pulmonary vasculature, and skeletal muscles. There is no definitive cure, and its course can be fatal in up to 5% of cases.
Within the last few years an association between the intravenous administration of gadolinium-based MR contrast agents and NSF has been documented. New and increasing information is being gathered every day about NSF and the use of gadolinium-based agents. The cause is unknown, but early evidence suggests that it may be due to dissociation of gadolinium from its chelate with deposition of free gadolinium in soft tissues. Although the information is early and incomplete, it has prompted a FDA warning about the use of gadolinium.
The vast majority of patients with NSF had severe (stage 4) or end-stage (stage 5) renal failure. This translates to a GFR between 15 and 29 mL/min/1.73 m2 (stage 4) or GFR < 15 mL/min/1.73 m2 or on dialysis (stage 5). Of all the cases of NSF associated with IV gadolinium administration, none have been documented in a patient with normal or mildly impaired renal function. The risk in moderate renal failure (GFR between 30 and 59 mL/min/1.73 m2) although still unknown, appears to be small. The estimated risk of developing NSF in a patient with severe or end-stage renal failure may be up to 3-5%.
Of the 5 FDA-approved gadolinium-based agents, >90% of cases of NSF have been associated with Omniscan. According to the ACR Guidance Document for Safe MR Practices, of the > 100 cases of NSF reported to the FDA MedWatch reporting system, 85 are Omniscan-associated, 21 are Magnevist-associated, and 6 are Opti-MARK-associated. A small number of reports of NSF have been made associated with Prohance and Multihance, but these patients also received Omniscan at some point prior to developing NSF.
It also has been noted that the development of NSF most commonly follows high-dose administration of gadolinium-based MR contrast agents. These double and triple doses are often used in contrast-enhanced MRA.
An official FDA alert first issued in January of 2006, again in December 2006, and most recently in May 2007 gives information and guidance to the public and health care providers about NSF and gadolinium. It states that those most at risk for NSF include patients with acute or chronic severe renal insufficiency (GFR <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. The FDA advises in its report:
How does this affect your patient and their MRI examination?
In those patients with a GFR of <30, several things may happen. The radiologist may contact the ordering physician to discuss the risks and benefits associated with gadolinium administration. If the radiologist cannot reach the ordering physician for any reason, or if he deems that contrast is not necessary for the examination, gadolinium will not be given.
If gadolinium is required in a patient who is already on dialysis, the referring clinician should arrange a dialysis session for that patient for the same day (preferably within a couple of hours of the MRI), and again 24 hours later.