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A preclinical study by Bower et al. found that gadolinium-based contrast agents (GBCAs) have a toxic effect on mitochondrial respiratory function and cell viability in human neurons. The study, Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases with Reduced Kinetic Stability of the Agent, was published online ahead of print in Investigative Radiology. For the study, neurons modeling a subset of those in the basal ganglia were tested, because the basal ganglia region is one of two brain regions that displays the greatest T1-dependent signal hyperintensity changes. Multiple studies have shown that T1-signal intensity changes in the brain are the result of gadolinium deposition. The authors noted that there is increasing evidence that all agents (linear and macrocyclic) remain in human brain tissue for some period of time, where they may be taken up into various cell types, including glia and neurons.
Reports of possible clinical symptoms experienced by patients after a contrast-enhanced MRI have been published. However, until this study, it was unknown whether GBCAs induce toxic effects on the cellular function of human neurons. This study provides the first definitive evidence that GBCAs induce mitochondrial toxicity and cell death in cultured human neurons. The authors said that the “magnitude of the measured toxicity broadly increases as the kinetic stability of the contrast agent decreases, and the lower stability agents induce toxicity at concentrations that fall within the range detected in some autopsy patients”. “For all agents, the magnitude of the toxicity increases with concentration.” (more…)
A recently released review article by Drs. Katarina Leyba and Brent Wagner, titled “Gadolinium-based contrast agents: why nephrologists need to be concerned”, doesn’t pull any punches when it comes to the use of gadolinium-based contrast agents (GBCAs) for contrast-enhanced MRIs. The authors said that ‘nephrogenic’ systemic fibrosis is a misnomer since GBCAs are the known trigger for the disease; kidney impairment is a risk factor. They note that “the experimental evidence demonstrates that gadolinium-based contrast agents are biologically active – that is, not inert”. Drs. Leyba and Wagner said that “because GBCAs are biologically active in vitro and in vivo, and patients with normal renal function have reported adverse events that overlap those of ‘nephrogenic’ systemic fibrosis (i.e., rash, muscle/tendon ‘tightness, pain…), and because the other risk factors are undetermined”, medical professionals need to be “open to the possibility that ‘nephrogenic’ systemic fibrosis and these gadolinium-based contrast agent-induced symptoms are part of a continuum”. (more…)
The National Center for Health Research (NCHR) recently published a new white paper on its website about gadolinium-based contrast agents (GBCAs). The title of the paper is “The Health Risks of Gadolinium-Based Contrast Agents used in MRIs” and the authors are Stephanie Fox-Rawlings, PhD, and Diana Zuckerman, PhD. The paper provides a detailed history of GBCAs from regulation, to gadolinium toxicity and its clinical effects, possible treatments, and environmental exposure.
While there is much that we know about gadolinium and GBCAs, the authors acknowledge that there are still uncertainties, but that “the research thus far suggests that some people with healthy kidney function have been harmed by gadolinium. This conclusion is based on the clear evidence of its accumulation and studies correlating its presence with symptoms”.
The authors pose several major questions concerning GBCAs and potential long-term harm. They also describe the difficulties involved with designing studies to answer those questions. However, they make it clear that new studies with carefully selected populations and study designs are needed.
Hopefully NCHR’s white paper about GBCAs will generate more research and interest in the potentially serious health risks associated with gadolinium retention and its long-term toxic effects.
About NCHR –
NCHR is a nonprofit, nonpartisan think tank that is focused on research that can improve the health of adults and children. They do not accept funding from companies that make medical treatments.
According to its website, NCHR focuses on the programs and policies that they believe can most benefit from the research-based information that they can provide and the attention that they can generate.
You can read the article and learn more about NCHR here –
Editorial by Sharon Williams
What difference does a name make? Evidently, when you are naming a disease it can make a huge difference. The name can limit the scope of medical research, and when it comes to gadolinium, it has the potential to exclude other patient populations who have been exposed to the same toxic metal.
In 1997, when a group of patients on dialysis developed what appeared to be a new skin disorder, it was called Nephrogenic Fibrosing Dermopathy (NFD). When researchers later learned that the problem went well beyond the patients’ skin and caused a systemic disease process, the name was changed to Nephrogenic Systemic Fibrosis (NSF). The word “nephrogenic” in the name caused doctors and researchers to focus on people with severe renal disease. At the beginning, that made sense since the problem only had been seen in patients with end-stage renal disease (ESRD). Later we learned more about the cause.
In 2006, nine years after NSF/NFD was first diagnosed, the connection was made between NSF and gadolinium-based contrast agents (GBCAs) administered for MRIs. Even though impaired kidney function did not cause NSF, the focus remained on the “N” or nephrogenic part of NSF. Patients with normal kidney function were being overlooked; however, they were not unaffected by retained gadolinium from GBCAs.