While the association between gadolinium-based contrast agents (GBCAs) and the development of adverse conditions such as nephrogenic systemic fibrosis (NSF) has been confirmed in patients with diminished renal function, more recent research indicates that gadolinium accumulates in the bone tissues, brains and kidneys of patients with normal kidney function.
The reasons for this accumulation—and the potential negative consequences for patients—are still largely unknown, due in part to limited existing clinical data regarding the mechanisms of gadolinium toxicity, wrote Moshe Rogosnitzky and Stacy Branch of the MedInsight Research Institute in New York, in a research review recently published in the journal Biometals.
“Unequivocal data regarding the effects of multiple GBCA exposure are limited,” they wrote. “However, the information regarding the thermodynamic stability constants for GBCAs, in vitro, animal, and human data, and the emerging data regarding gadolinium tissue accumulation in those with normal kidney function indicate that the potential toxicity associated with GBCA must be seriously and urgently considered.”
Rogosnitzky and Branch cite findings from various recent studies into gadolinium toxicity, including a patient-advocacy group survey in which former patients with repeated exposure to GBCAs reported experiencing neurological, musculoskeletal, or dermal symptoms, including pain (100 percent), muscle symptoms (88 percent) and ocular symptoms (76 percent).
“The results … show the onset of a group of symptoms within a month of their last MRI,” they wrote. “This information can serve as a guide for retrospective and prospective studies to determine associations between multiple GBCA administration and adverse health effects,” they wrote.
While the authors cite other examples of recent research showing evidence of gadolinium deposits in animals and tissues of deceased patients, the mechanisms of toxicity stemming from GBCAs has yet to be confirmed in living human subjects.
But despite inconclusive evidence and a lack of consensus on whether disassociated gadolinium causes negative health outcomes, Rogosnitzky and Branch conclude that current research merits more studies into the toxicity mechanisms of GBCAS to further investigate how to ensure patient safety without compromising diagnostic capability.
“This concept must be addressed with retrospective and prospective cohort studies,” they wrote. “Research providing additional mechanistic data is also paramount and will provide valuable information regarding how to prevent GBCA-related toxicity, treat existing GBCA-related health issues, guide the use of existing GBCAs, and direct the design of safer MRI contrast agents.”