Editorial – May 25, 2017
I am very disappointed and frustrated by the May 22, 2017, FDA Safety Announcement about gadolinium-based contrast agents (GBCAs). I am beginning to wonder how many more people must be adversely affected by retained gadolinium before the FDA decides to take decisive action.
Personally, I don’t blame the FDA or radiologists for what happened to NSF patients. What happened to those patients was terrible, but I want to believe that no one knew then just how unstable the linear agents are, especially when they remain in the body for longer periods of time like they might do in renally-impaired patients. However, once the connection between NSF and GBCAs was discovered in 2006, that all began to change. No longer could the FDA and radiology community say that they didn’t know that gadolinium might be retained from MRI contrast agents or what it might do to the human body when that occurred.
From 2006 until the end of 2013, the FDA and medical community thought that only patients with severe renal problems were at risk of retaining gadolinium. Warnings were issued and action was taken to better screen renally-impaired patients and reports of new cases of Nephrogenic Systemic Fibrosis (NSF) dropped dramatically. However, no one seemed to be investigating what might happen when less gadolinium was retained such as what might occur in patients with “normal” renal function or eGFRs greater than 60.
Since December of 2013 and the first paper by Kanda and his colleagues, the evidence has been mounting that clearly shows that patients with normal renal function retain gadolinium in their brains, bones, and elsewhere in their bodies. This seemed to be news to the FDA and radiology community, but it was something that patients affected by gadolinium have long been trying to tell their doctors. I first brought it to the attention of the FDA in my letter of October 23, 2012. In that letter, I noted that evidence of gadolinium retention in patients with normal renal function was reported by Gibby et al. in 2004 – that was 13 years ago, and it occurred after administration of both a linear and a macrocyclic GBCA.
The published literature clearly states that “gadolinium is toxic”. The FDA has acknowledged that “all GBCAs may be associated with some gadolinium retention in the brain, and other body tissues”. So why is it okay to keep injecting the least stable gadolinium-based contrast agents into patients when it is highly likely that those people are going to retain some unknown amount of a toxic metal? Gadolinium is a toxic metal that has been found to be neurotoxic, to impair mitochondrial function, induce oxidative stress, and much more. Researchers are looking for histological changes in the brain, but what about functional changes?
The Safety Announcement talks about changes to OptiMARK’s product label, but what good does that do? Patients never see the product label and even if they did it does not include any new “Black Box” warning that might draw their attention and cause them to ask questions. Informed Consent does not seem to apply when it comes to having an MRI or MRA with contrast. Most people have never heard about the issues surrounding the safety of gadolinium-based contrast agents or the possible long-term effects of retained gadolinium so they agree to the procedure without being fully-informed. In my opinion, the patient needs to be fully-informed of all possible risks involved.
How does the FDA’s National Center for Toxicological Research (NCTR) explain the long-term excretion of gadolinium that has been reported by patients? Is it really that difficult to believe that someone’s otherwise unexplained symptoms aren’t somehow linked to the gadolinium that is still being excreted 10+ years after their only MRI with contrast? That patient and others I know need to have their cases fully-investigated by trained researchers. Patients who have retained gadolinium can communicate what they are experiencing – lab rats cannot.
The Safety Announcement said the public would be notified when the FDA plans to have a public meeting to discuss this issue. On behalf of all the affected patients I know, I am requesting that the FDA hold a public meeting on the issue of gadolinium retention and GBCA Safety before the end of 2017. I am also requesting that I be informed of the date well in advance so that I can attend with other patients who have been affected by retained gadolinium.
With every day that goes by, more and more unsuspecting adults and children are exposed to GBCAs and put at risk of retaining gadolinium with unknown long-term consequences. This cannot be allowed to happen any longer. I believe we are at the point when no one can honestly say that they “did not know about gadolinium retention from GBCAs” or that “gadolinium is toxic”. The FDA and the radiology community are well-aware that there are serious questions about GBCA safety, and they are aware of the patient groups that have reported evidence of long-term gadolinium retention and symptoms of gadolinium toxicity. The problem of gadolinium retention from MRI contrast agents is very real and it must be taken much more seriously.
If the FDA will not take decisive action on the use of gadolinium-based contrast agents, I am calling on leaders within the radiology community to do something to ensure that patients are no longer put at unnecessary risk. It only takes one dose of a GBCA to change a life forever – I know many people who can attest to that. In my opinion, failure to act is no longer an option or morally acceptable.
FDA Safety Announcement, May 22, 2017. https://www.fda.gov/Drugs/DrugSafety/ucm559007.htm
Kanda, T., Ishii, K., Kawaguchi, H., Kitajima, K., & Takenaka, D. (2013). High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-weighted MR Images: Relationship with Increasing Cumulative Dose of a Gadolinium-based Contrast Material. Radiology, 131669. doi:10.1148/radiol.13131669. Retrieved from http://pubs.rsna.org/doi/abs/10.1148/radiol.13131669
Gibby, W. A., Gibby, K. A., & Gibby, W. A. (2004). Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Investigative Radiology, 39(3), 138–42. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15076005