Devastating disease raises questions about MR safety

August 1, 2007

show of hands from the audience at a special ISMRM/ESMRMB symposium on nephrogenic systemic fibrosis said a lot without saying a word about the growing prevalence of this condition among patients who have undergone gadolinium-based contrast-enhanced MR imaging.

A show of hands from the audience at a special ISMRM/ESMRMB symposium on nephrogenic systemic fibrosis said a lot without saying a word about the growing prevalence of this condition among patients who have undergone gadolinium-based contrast-enhanced MR imaging.

At least 30 hands went up when Dr. Shawn Cowper, a Yale University dermatopathologist, asked radiologists if they have cases that have not yet been submitted for entry into a registry. As of June 1, Cowper had analyzed and confirmed 239 cases of the condition first identified 10 years ago. The audience response told him that the total will grow.

The ISMRM and ESMRMB convened the symposium to establish the facts on NSF and to offer recommendations on how radiologists can best minimize risk. Panelists included Cowper and Dr. Henrik S. Thomsen, a professor of radiology at Copenhagen University. They are custodians of the two largest patient registries of the disease and experts on NSF epidemiology.

NSF is a painful, debilitating, potentially fatal skin disorder that has been linked to chelated gadolinium contrast media administered prior to MRI in patients with renal disorder. All cases since the first diagnosed in San Diego in 1999 have involved patients with severely impaired renal function. A potential association between NSF and gadolinium-based contrast agents was first described in early 2006. Symptoms emerged within two months after patients were administered a gadolinium-chelate contrast medium before undergoing MRI.

Although medical records are often incomplete, Omniscan (gadodiamide) is associated with 85% of the documented NSF cases in Cowper's registry. Magnevist (Gd-DTPA) is involved in about 10% of the incidents. Other agents, such as OptiMARK, a gadolinium-chelate agent made by Mallinckrodt Imaging, have also been implicated, but most of those cases are anecdotal, Cowper said.

In a March 2007 white paper, GE Healthcare reported that 120 cases of NSF had been linked to Omniscan. As of May 10, Bayer Schering Pharma and its affiliates had received and evaluated 77 reports of patients who reportedly developed NSF after administration of its best-selling Magnevist agent.

Thomsen has documented 26 cases in Europe and has found references to 120 cases in the peer-reviewed literature. He estimates that 1000 people have developed gadolinium-related NSF and that 200 have died. He also estimates that 3% to 7% of patients with renal failure will develop the symptoms of NSF after Omniscan administration.

Manufacturers in the U.S. are complying with FDA recommendations for a "black box" warning on product packaging for all gadolinium-based MR contrast products. The agency advises against the use of gadolinium-based contrast in patients with severe or chronic renal insufficiency or acute renal insufficiency of any severity due to hepatorenal syndrome. The contrast should also be avoided around the time of liver transplantation.

In the European Union, the European Agency for the Evaluation of Medicinal Products issued in February a strict contraindication to Omniscan in patients with severe renal dysfunction and ordered a warning for all gadolinium products. Its investigation is ongoing.

Toshiba Medical Systems, an MR scanner manufacturer, has issued recommended noncontrast MR angiography protocols.

At least a dozen personal injury law firms in the U.S. are soliciting cases on the Internet and in late-night television advertising. As of June 15, Bayer and GE had each been sued once for separate incidents. The law firm Burg Simpson Eldredge Hersh & Jardine claimed to represent more than 20 individuals affected by NSF.

What can practicing radiologists do to protect their patients and themselves? Patients should be screened for end stage renal disease, diabetes, and hypertension before imaging, according to Dawson. Patients should also disclose that they are taking nephrotoxic drugs or have a history of gout, proteinuria, or renal surgery. For such patients, noncontrast MRI or multislice CT should be considered as an alternative.

Dr. Harm Peters, a nephrologist from Charite School of Medicine in Berlin, recommended strong, narrow indications for gadolinium contrast. When gadolinium is necessary for patients with a history of renal failure, he suggests that radiologists administer the lowest possible dose. They should correct for acidosis and perform dialysis in three sessions over three days following MRI.

Most panelists agreed that more data are needed before they would feel any confidence about framing recommendations concerning MR contrast dosage. Opinions concerning the value of hemodialysis were also mixed. Some panelists supported using it soon after contrast-enhanced imaging for patients with renal failure, and others said it is too soon to venture an opinion.