New ACR guidelines warn against Omniscan MR contrast use in patients with any kidney disease

March 2, 2007

Patients with any stage of renal disease should not receive the MR gadolinium contrast agent Omniscan, to help prevent a rare and life-threatening skin disease, according to new, comprehensive MR Safe Practice Guidelines from the American College of Radiology.

Patients with any stage of renal disease should not receive the MR gadolinium contrast agent Omniscan, to help prevent a rare and life-threatening skin disease, according to new, comprehensive MR Safe Practice Guidelines from the American College of Radiology.

Cautious use is advised for other gadolinium agents in patients with moderate to end-stage kidney disease, according to the guidelines, published online by the American Journal of Roentgenology Feb. 27.

Research indicates that patients with moderate to severe kidney disease may develop nephrogenic systemic fibrosis (NSF) after an MRI or MR angiography study with gadolinium-based contrast media. NSF causes musculoskeletal joint problems. In some cases, it quickly results in loss of mobility or death.

Five gadolinium contrast agents are FDA-approved for MRI: Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance. A contrast medium is often used on an off-label basis for MRA studies. Most cases of NSF have been linked to Omniscan, and some have also been reported for Magnevist and OptiMARK, said Dr. Emanuel Kanal, head of the ACR MR Safety Committee and lead author of the AJR paper.

The ACR guidelines strongly recommend prompt hemodialysis after a contrast-enhanced MR study only in patients who are already on hemodialysis. Radiology departments must coordinate with the dialysis units to ensure that patients begin hemodialysis immediately after the MR study, Kanal said in an interview. Kanal is the director of MR services at the University of Pittsburgh Medical Center.

In some important respects, the ACR guidelines directly conflict with previously issued advice from regulatory agencies in the U.S. and in Europe.

The FDA warned against gadolinium agents as a class, rather than singling out Omniscan. The FDA also advised providers to consider prompt hemodialysis in all patients with moderate to severe kidney disease.

"This is neither a practical nor scientifically sound recommendation," Kanal said.

NSF is very rare. It occurs in an estimated 3% to 5% of patients with severe renal disease after administration of Omniscan, which is believed to be the riskiest agent. NSF has been reported for a few patients with moderate stage disease, based on glomerular filtration rates, but at least some of these involved acute kidney injury (AKI). GFR measurements are notoriously unreliable in these patients, so it is unclear if renal disease was in fact moderate or more severe at the time the gadolinium contrast was administered.

"You can't expect that GFR will accurately portray renal function in patients with rapidly changing kidney injury," Kanal said.

For patients not already on hemodialysis, the initiation of the process carries risks. These risks may not be justified by the potential benefits of hemodialysis for patients with moderate chronic kidney disease, because NSF is extremely rare for this patient population, according to Kanal and other guideline authors.

ACR guidance also conflicts with guidance issued in February from the European Medicines Agency, the European equivalent of the FDA. This agency advised that Omniscan and OptiMARK are contraindicated in patients with severe kidney disease. The agency also concluded that hemodialysis is not recommended after an MRI study.

The European guidance appears to primarily be based on one key study that showed hemodialysis did not prevent NSF in three patients undergoing MRI with a double dose of Omniscan (AJR, 2007;188:1-7), Kanal said.

However, Kanal's personal communications with the study authors revealed that in two patients, hemodialysis was not initiated until nine and 18 hours after the contrast administration. Information was not available for the third patient.

Delayed hemodialysis could explain why a protective effect was not shown, Kanal said.

Certainly, the study results do not warrant recommending against immediate postprocedure hemodialysis in hemodialysis patients, he said.

"The Europeans go to the opposite extreme from the FDA in saying that they are not convinced hemodialysis helps after MRI. We [authors of the ACR guidelines] disagree strongly with this guidance and recommend immediate hemodialysis for hemodialysis patients receiving gadolinium-based MR contrast agents, as soon as the MR examination is completed," Kanal said.

New ACR Practice Guidelines also advise the following measures to help prevent NSF:

  • Prior to MR, all patients should be asked about their history of kidney disease or dialysis. However, screening for serum creatinine levels and GFR is not required in the general patient population.

  • Aside from avoidance of Omniscan, no special handling is required for patients with stage 1 or stage 2 kidney disease.

  • In patients with known moderate to end-stage kidney disease or AKI, a written order from the radiologist must be obtained for a contrast-enhanced MR study. Informed consent should be obtained from patients.

  • In patients with moderate to severe (stages 3 to 5) kidney disease or AKI, a risk-benefit analysis should be performed to determine if study benefits outweigh risks. If the study gets the go-ahead based on this analysis, the lowest dose (half dose or less if clinically possible) should be used to achieve the desired diagnostic result.

Providers should be aware that the risk of developing NSF may be greater with higher doses of gadolinium, which may be administered during peripheral MRA on an off-label basis and for approved uses, such as assessment of metastatic disease. However, it is also important to strike a balance between cautious use of gadolinium and provision of potentially life-saving contrast-enhanced studies, according to Kanal.

For more information from the Diagnostic Imaging archives:

European authorities warn against use of Omniscan in at-risk patients

FDA renews warning on gadolinium in patients with weak kidneys

Gadolinium-related problems stem from one specific agent

Europeans find more gadolinium related adverse reactions