Risk of Nephrogenic Systemic Fibrosis Appears Low With Newer Gadolinium Agents

By Will Boggs MD

June 30, 2020

NEW YORK (Reuters Health) - The risk of developing nephrogenic systemic fibrosis (NSF) after exposure to gadolinium agents appears to be low, at least among people with normal kidney function, according to a systematic review.

"The main take-home message from this evidence synthesis is that, in the meantime while we await more rigorous studies, physicians should consider adopting a patient-centered approach to decision-making regarding use of gadolinium-based contrast agents," said Dr. Joseph Lunyera of Duke University School of Medicine, in Durham, North Carolina.

"For instance, one such patient-centered approach could weigh a patient's need for contrast during imaging against their unique clinical profile, including degree and chronicity of kidney dysfunction," he told Reuters Health by email.

NSF, a debilitating condition caused by collagen deposition in soft tissues and internal organs, is associated with exposure to gadolinium-based contrast agents (GBCAs) administered during MRI or angiography scans. There is no definitive treatment, and the condition is often fatal.

Newer GBCAs, with relatively greater stability in their gadolinium-ligand bond, are thought to carry a substantially lower risk of NSF, but uncertainties remain.

Dr. Lunyera and colleagues evaluated the NSF risk with newer versus older GBCAs across the spectrum of kidney function in their systematic review of 34 articles reporting on 32 studies.

In their paper, they refer to newer GBCAs, such as gadoteridol or gadofosveset trisodium, as American College of Radiology (ACR) group-II or -III agents and older GBCAs, such as gadopentate dimeglumine or gadodiamide, as ACR group-I agents.

Among more than 83,000 individuals in 20 studies exposed to ACR group-II and -III agents, there were no cases of NSF, the researchers report in Annals of Internal Medicine.

The risk of bias was high in 12 of these studies and unclear in the other eight.

In the 12 studies that allowed comparison of NSF rates between group-I and group-II and -III agents, there were 37 NSF cases after more than 110,000 index exposures to group-I agents and four NSF cases after 8,499 index exposures to group-II agents (no patient had an index exposure to a group-III agent).

The upper limits of the 95% confidence intervals were between 0.001 and 0.0672 cases for older GCBAs and between 0.0018 and 0.0204 cases for group-II GBCAs.

Data were very limited for patients with chronic kidney disease risk factors or for patients with any degree of kidney disease.

Overall, the researchers rated the certainty of evidence low to very low.

"While the finding that NSF risk was greater after exposure to older compared to newer GBCA had been seen in previous studies, the current study demonstrated that the exact upper confidence interval around NSF risk was similar between these two GBCA groups," Dr. Lunyera said. "The implication of this finding for clinical practice is that clinicians should exercise caution when making decisions pertaining to use of GBCAs - including the newer and presumably safer agents."

"None of the studies assessed NSF risk specifically among patients with acute kidney injury or those with key risk factors for chronic kidney disease, such as diabetes and hypertension," he said. "These limitations warrant additional investigations in future studies to provide conclusive data to inform clinical decision-making regarding use of gadolinium-based contrast agents."

Dr. Martin Prince of Columbia University College of Physicians and Surgeons, in New York City, who recently reviewed 639 patients with biopsy-confirmed NSF, told Reuters Health by email, "For the newer group-II GBCAs, the risk of NSF is between 1:4000 to 1:million. These data are giving a promising indication that the NSF risk with group-II GBCA is very low."

"If someone with poor renal function really needs a GBCA-enhanced MRI exam, we have good options for NSF-risk minimization," said Dr. Prince, who was not involved in the review.

Dr. Jonathan Kay of UMass Memorial Medical Center and the University of Massachusetts Medical School, in Worcester, who has also researched gadolinium-induced fibrosis, told Reuters Health by email, "Definitive conclusions about the safety of macrocyclic GBCAs cannot be drawn from this systematic literature review because of the methodologic limitations of the studies included, which relied upon passive case finding, and the limited number of patients with underlying kidney disease that were enrolled in these studies."

"Concluding that there is virtually no risk of NSF following the administration of macrocyclic GBCAs, based upon studies that depended only upon medical-record documentation to identify cases of NSF, contributes to a false sense of security when using these contrast agents, especially in patients with underlying chronic kidney disease," said Dr. Kay, who also was not involved in the new work.

"GBCAs should be avoided in patients with underlying kidney disease," he said. "However, if a patient with chronic kidney disease requires an MRI study that must be enhanced with contrast to acquire necessary diagnostic information that cannot be obtained in any other way, a macrocyclic GBCA should be used."

The study had no commercial funding,

SOURCE: https://bit.ly/3dnKec5 Annals of Internal Medicine, online June 23, 2020.