Gadolinium-related cases may be higher than expected
Research eyes NSF, kidney failure relationship
About 500 documented cases of nephrogenic systemic fibrosis (NSF), a painful condition that affects skin and internal organs, have been reported worldwide. However, that number is very likely an underestimation.
"There are probably a lot of cases that haven't been diagnosed," says Jeffrey Weinreb, MD, a vice president with the American College of Radiology and professor of radiology at the Yale University School of Medicine in New Haven, CT.
In fact, cases of NSF have been found to be higher than initially contemplated — even from a year earlier — among patients with renal conditions who were exposed to gadolinium-containing contrast agents during magnetic resonance (MR) procedures, according to a recent study from Massachusetts General Hospital in Boston. Analysis by the hospital's researchers noted that hemodialysis patients who had undergone imaging studies using the contrast agent had more than 10 times the risk of developing NSF when compared with patients with no exposure to gadolinium. In addition, individuals with NSF reportedly faced a three- to five-times greater risk of dying within two years when compared with patients without the condition from the same dialysis centers, they reported in Arthritis & Rheumatism.1
The disease was first detected in 1997 and written about in a paper three years later by Shawn Cowper, MD, now an assistant professor of dermatology and pathology at Yale. But, it took until 2006 when the connection between imaging contrasts with gadolinium and the onset of NSF —a debilitating disease that involves hardening of the skin, muscle pain, and stiffened joints — came to the public's attention: A large scale report from Denmark found that 13 out of 380 patients with kidney disease who had been imaged with gadolinium developed NSF.2
By December 2006, the Food and Drug Administration (FDA) had received 90 reports of patients with moderate or end stage renal disease who developed NFS within days and months of exposure to gadolinium during an imaging process.
For Cowper, who continued to gather and analyze cases through the registry of the International Center for NFD/NSF Research (ICNFDR), which is located at Yale, these reports to the FDA confirmed suspicions about a link of NSF to a contrast agent. (For more information, go to www.icnfdr.org.) The initial problem was that many patients were unaware that they had been exposed to gadolinium: Either the patients' memories were poor, they were in a coma, or they didn't make a connection that they were injected with gadolinium prior to an imaging procedure, he says.
"We're finding that there has been a pattern of not-very-good recordkeeping in general, which is making this investigation much more complex than it needs to be in this country," Cowper says.
Cowper has been reviewing a wide variety of queries coming into the registry. Many are from attorneys — and many are from patients "who wish there was an explanation for their chronic disease." And there is data showing a link between gadolinium use and NSF. "That's what I try to prevent by going around lecturing," he says. "It's a fairly wide-ranging problem, not just a problem with dermatologists, pathologists, nephrologists, or radiologists. You get into transplant people, rheumatology, pediatrics…It's a pretty wide-ranging disease in terms of how it affects physicians."
Even with the small numbers of patients involved overall, activities to prevent NSF from occurring in patients with renal conditions has been swift. In May 2007, the FDA issued a "black box" warning the risk of NSF associated with the five gadolinium-based contract agents (Omniscan, OptiMARK, Magnevist, MultiHance, and ProHance) among patients with acute or chronic severe renal insufficiency. Also, the manufacturers issued a "Dear Healthcare Professional" letter in September to inform them of revisions.
The American College of Radiology's Contrast Committee and the Subcommittee for MR Safety recommended in July 2007 to prescreen patients prior to the administration of gadolinium-based contrast agents.
Many health care facilities have instituted their own procedures to avoid the potential occurrence of NSF among renal patients. For instance, Yale-New Haven Hospital uses its order-entry system that looks at various factors to determine if a gadolinium-based contrast can be used for hospitalized patients. The factors that are looked at are the estimated Glomerular Filtration Rate (eGFR), a measure of renal function, and medical history.
If the eGFR is below 30 (a threshold set by the hospital) and if the patient is on dialysis or has severe liver disease, a contrast with an MR will not be scheduled unless the patient has a nephrology consult or hepatology consult. Those physicians, consulting with a radiologist, will look at the "benefit and the risk and whether there are alternative ways of getting a diagnosis without administering the gadolinium contrast," Weinreb says.
For outpatients, schedulers have been trained to ask patients about the risk factors for chronic kidney disease. They are also asked about age (if they are older than age 60), and if they have a history of hypertension, diabetes, or kidney-related problems. If they respond yes to any of those questions, they are required to submit eGFR prior to being scheduled for an MR.
The risk related to getting NSF from a sole dose of gadolinium "is really very, very small," Weinreb says. "But nevertheless, we decided here that we don't just want to limit the risk. We want to do whatever we can to eliminate the risk."
References
- Todd D, Kagan A, Kay J, et al. Cutaneous changes of nephrogenic systemic fibrosis: predictor of early mortality and association with Gadolinium exposure. Arthritis Rheumatism 2007; 56:3,433-3,442.
- Grobner T. Gadolinium: specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis. Nephrol dial Transplant 2006; 21:1,104-1,108.
Resources
To obtain information on gadolinium-containing contrast agents from the Food and Drug Administration (FDA), go to www.fda.gov. To obtain the FDA letter to health care professionals on drug warning for gadolinium-based contrast agents, go to www.fda.gov.
For an American College of Radiology (ACR) publication titled ACR Guidance on MR Safe practices: 2007, with updated ACR screening recommendations on gadolinium-based MR contrast agents, go to www.acr.org.
About 500 documented cases of nephrogenic systemic fibrosis (NSF), a painful condition that affects skin and internal organs, have been reported worldwide. However, that number is very likely an underestimation.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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