A study assessing the risks of nephrogenic systemic fibrosis after exposure to gadolinium recommends that physicians weigh the need for imaging against the severity and chronicity of a patient’s kidney disease.

A team of physicians and researchers, many from Duke Health, concluded that the risk of nephrogenic systemic fibrosis (NSF) related to newer gadolinium formulations is relatively low for patients with normal kidney function. The study was published in July 2020 in Annals of Internal Medicine. Gadolinium-based contrast agents (GBCAs) are used for some MRI scans.

Lead author Joseph Lunyera, MBChB, MSc, a Duke clinical epidemiologist specializing in nephrology research, cautions that patients with kidney disease are at greater risk based on the study’s review of outcomes. When older GBCA formulations are used, the risk seems to be greater, he says.

However, when the researchers compared NSF risk of newer and older GBCAs in their systematic review of 32 studies, they noted that the confidence intervals surrounding estimates overlapped between newer and older formulations. A cautious approach is prudent even when newer and presumably safer GBCA formulations are used, says Karen M. Goldstein, MD, MPH, senior author of the study. A Duke general internist, Goldstein is co-director of the Durham Veterans Affairs Evidence Synthesis Program, which conducted the study. Both authors acknowledged the need for additional investigation.

Newer GBCAs have greater molecular stability in the gadolinium-ligand bond and, as a result, are believed to present lower risk for NSF. But Lunyera says many uncertainties remain about the use of GBCAs, which have been associated with NSF since 2006. The rare but debilitating condition involves fibrosis of skin, joints, eyes, and internal organs. There is no definitive treatment and the condition is often fatal.

“Our primary message from this evidence synthesis is that physicians should consider a patient-centered approach to the use of these contrast agents,” Lunyera says. “We need to see more research, obviously, but GBCAs present risk that should be discussed individually, particularly when a patient has impaired kidney function.”

The use of the contrast agent and its consequences remains a global health concern, Lunyera says, because there are few guidelines directing the use of GBCAs in North and South America, Europe, and Asia. The American College of Radiology, however, has issued formal directives about the risk of GBCAs.

Lunyera says the patient’s degree of kidney dysfunction should be a factor in the decision about use of a GBCA. Another consideration is how long the gadolinium remains in the body. “Longer exposure adds risk,” he explains.

“We are dealing with very rare outcomes and with a condition that currently has no cure, which adds to the importance of these findings,” Lunyera says. “To avoid the consequences of NSF, clinicians must develop risk profiles for each patient. That’s our key point.”