Evidence is mounting that gadolinium-based MR agents can cause nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD)—something radiologists need to put on their radar screen. Such was the message of the panel discussion on Monday at the 93rd annual meeting of the Radiological Society of North America (RSNA) this week in Chicago. The panel discussion, “Gadolinium Toxicity: Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy—A Lethal Threat to Patients with Renal Insufficiency,” was moderated by Emanuel Kanal, MD, FACR, FISMRM, director, magnetic resonance services and professor of radiology and neuroradiology, department of radiology, University of Pittsburgh Medical Center.
“We have been relatively confident all along that increasing the administered dose of a gadolinium-based MR contrast agent (GBMCA) for patients with severe or end-stage chronic kidney disease (CKD) increases the likelihood of a patient developing NSF. However, relatively new data from several more recent articles in the peer-reviewed literature now strongly suggest that cumulative doses of administered GBMCA (over an as yet undefined time period, possibly even a lifetime) seems to play a role in determining not only the likelihood of developing NSF, but also the severity of the clinical case of NSF that will be developed/experienced,” Kanal said. “This suggests that radiologists may likely imminently have to start grappling with the concept of identifying total, possibly lifetime, prior-administered GBMCA dosages to patients with significant renal disease prior to deciding on whether or not to administer any GBMCA in the future and, if so, which one and how much to administer.”
Providing the nephrology input at the special session was Georges Saab, MD, assistant professor of clinical medicine, University of Missouri, Columbia, while Leonard Lucey, JD, legal counsel for the American College of Radiology, addressed the key legal considerations. Lucey was not the only attorney present; Kanal said he recognized at least three other attorneys in the audience representing both sides of the issue.
“With the tremendous interest I have seen from attorneys representing both sides of the NSF cases and with the active advertising for NSF clients by plaintiff attorneys, I thought it would be interesting for the course attendees to get a legal analysis of where we stand today,” said Kanal. Currently, there are lawsuits in progress with more likely to follow with more information coming available.
The potential product liability issue with the possibility of a medical malpractice issue is sure to get the attention of radiologists. Kanal pointed to the Sept. 12 joint letter from pharmaceutical companies distributing FDA-approved MR contrast agents that advised providers of a potential association with the administration of any GBMCAs to patients with severe or end stage chronic renal disease and the subsequent development of NSF. In Lucey’s presentation, he explained that this seemed to shift much of the legal liability from the pharmaceutical firms to the physicians administering these agents. Kanal noted that in subsequent discussions with many who attended this session, this observation “seems to have proven quite eye-opening to most radiologists in attendance.”
As of last week, more than 450 NSF cases had been reported to the FDA MedWatch reporting system.
The greatest risk is to patients with significant renal disease, most especially those with stage 5 CKD, and perhaps some with stage 4 CKD. Additionally at risk are patients with acute renal failure/acute kidney injury who receive any GBMCA, but especially those who receive a linear GBMCA and, it seems, especially those who receive Omniscan. Approximately 3 to 7 percent of stage 5 CKD patients who receive a higher dose of Omniscan have been diagnosed with NSF. Other cases have been reported with the administration of Magnevist or Optimark, though not as many as those who reportedly received Omniscan. Only one report may be tied to repeated high dose Prohance and there are no cases related to having received only Multihance.
“Gadolinium has been observed in NSF patient tissue biopsies as long as at least 3 years subsequent to that patient's most recently recorded administration of a GBMCA,” said Kanal. The likely mechanism setting off NSF in renal disease patients is the theory of transmetallation—the separation over time of the gadolinium ion from its