Update on Gadolinium-Based Contrast Agent Safety, From the Special Series on Contrast Media.

Since its introduction more than 35 years ago, gadolinium-enhanced MRI has fundamentally changed medical practice. Although extraordinarily safe, gadolinium-based contrast agents (GBCAs) may have side effects. Four distinct safety considerations include acute allergiclike reactions, nephrogenic systemic fibrosis (NSF), gadolinium deposition, and symptoms associated with gadolinium exposure. Acute reactions after GBCA administration are uncommon-far less than with iodinated contrast agents-and, although rare, serious reactions can occur. NSF is a rare but serious sclerodermalike condition occurring in patients with kidney failure after exposure to American College of Radiology (ACR) group I GBCAs. Group II and III GBCAs are considered lower risk, and, through their use, NSF has largely been eliminated. Unrelated to NSF, retention of trace amounts of gadolinium in the brain and other organs has been recognized for over a decade. Deposition occurs with all agents, although linear agents appear to deposit more than macrocyclic agents. Importantly, to date, no data show any adverse biologic or clinical effects from gadolinium deposition, even with normal kidney function. This article summarizes the latest safety evidence of commercially available GBCAs with a focus on new agents, discusses updates to the ACR NSF GBCA safety classifications, and describes approaches for strengthening the evidence needed for regulatory decisions.