There have been concerns in the United States recently about the possible harmful side effects from absorbing gadolinium-based contrast agents (GBCAs) into the body during some magnetic resonance imaging (MRI) exams. The popular press, patient advocacy groups, and a recent lawsuit continue to raise public anxiety about the use of GBCAs. To address some of the anxiety and concerns over this issue, Paul Jannetto, Ph.D., DABCC, FAACC, and Joshua Bornhorst, Ph.D., DABCC, FAACC, Co-Directors of the Mayo Clinic Metals Laboratory and leading experts in this field, have compiled the following list of the most up-to-date information. Why Is Gadolinium Exposure Drawing So Much Attention? The increased media and regulatory attention is, in large part, due to several safety announcements in 2017, released by the U.S. Food and Drug Administration (FDA)—via its MedWatch system—regarding the use and retention of GBCAs in patients who have had an MRI. This attention particularly peaked after the announcement in December 2017, when the FDA, after review and consultation with the Medical Imaging Drugs Advisory Committee, decided to require a new class warning and other safety measures for all GBCAs used for MR imaging. (Note: GBCAs are only used in 30% to 50% of MRI exams—exposure is based on a clinical assessment of each patient’s risk and tolerance for this metal.) The new warning concerns the fact that gadolinium can be retained in patients’ bodies (e.g., the brain and other tissues) for months to years after receiving these drugs. Several research studies have shown that GBCAs may be associated with some gadolinium retention in the brain and other body tissues, despite normal renal function. However, most GBCAs are cleared in the first 96 hours after being administered to a patient. Amid all the attention, experts like Dr. Jannetto remind everyone that, “At this time, regardless of the GBCAs utilized, prolonged gadolinium retention has still not been directly linked to adverse health effects in patients with normal kidney function.” The December FDA announcement also noted that there are differences in the two types of GBCAs used (i.e., linear and macrocyclic). Of the two, linear agents result in more retention of gadolinium in patients—and retention for a longer period of time versus macrocyclic GBCAs. Regardless of the new warning, the FDA concluded that the benefits of the approved GBCAs continue to outweigh any potential risk. And the European Medicines Agency reached a similar conclusion. Even so, a number of sources continue to cast gadolinium in an unsettling light. What Gadolinium Tests Are Available, and When Should They Be Ordered? Measurement of gadolinium in clinical laboratories is not routinely conducted nor formally recommended by the FDA or any professional practice guidelines. “It should also be noted that there is no definitive or diagnostic test for gadolinium toxicity,” says Dr. Bornhorst. “Nevertheless, Mayo Medical Laboratories currently offers gadolinium testing in serum, urine, and dermal tissue.” The test is performed by inductively coupled plasma mass spectrometry (ICP-MS), which provides a total gadolinium concentration regardless of the form used. Serum testing may be useful to monitor exposure to gadolinium. Urine testing (either a 24-hour collection reported as micrograms of gadolinium per 24 hours, or a random collection, which is reported as micrograms of gadolinium per gram of creatinine) may be useful to assess chronic exposure and monitor effectiveness of dialysis. Dermal tissue also may be used to evaluate exposure to gadolinium. What Does the Test Result Mean? Again, Drs. Jannetto and Bornhorst stress that there is no definitive or diagnostic test for gadolinium toxicity. Therefore, the presence of gadolinium in serum or urine, greater than 96 hours after the administration of a GBCA, only confirms past exposure and/or prolonged elimination of gadolinium by the renal system. “Gadolinium also has been shown to be present in municipal water sources,” says Dr. Jannetto. “And this might contribute to the observation of low concentrations of gadolinium in patients who have never been exposed to GBCAs. Ultimately, patients should consult with their health care providers to interpret any test results.” What Is the Connection involving Gadolinium, Nephrogenic Systemic Fibrosis (NSF), and Renal Dysfunction? Gadolinium is primarily eliminated by the kidneys, and impaired renal function may be a contributing reason why it can be retained in the body longer than 96 hours. Although ongoing studies continue to examine if there are any potential adverse effects of the long-term retention of gadolinium, the only known adverse health effect to date related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis (NSF). “NSF is a relatively uncommon condition where fibrous plaques develop in the dermis and, often, in deeper connective tissues,” says Dr. Bornhorst. “It’s a painful skin disease characterized by a thickening of the skin, and it can involve the joints and cause significant limitation of motion within weeks to months.” Reported cases of NSF have occurred almost exclusively in a small subgroup of patients with severe renal disease, and almost all have been associated with prior use of GBCAs. The good news is that, over the past decade, changes in clinical practice guidelines have almost completely eliminated the incidence of NSF. However, the association of NSF and observed elevated gadolinium concentrations is still not fully understood. For more detailed information about ordering gadolinium testing, please refer to the Mayo Medical Laboratories Laboratory Test Catalog.