Harman and colleagues1 recently reported a diffuse decrease in the signal intensity of T2-weighted images in the liver, spleen, bone marrow, and adrenal glands of a 59-year-old woman treated for iron-deficiency anemia with intravenous ferumoxytol (licensed in the United States as Feraheme and in Europe as Rienso) 50 days before abdominal magnetic resonance imaging (MRI) for unexplained chronic abdominal pain. The images mimicked hemosiderosis but were in fact due to interference with MRI. This situation is well described in the label of this iron product, which states the need for an interval of at least 90 days between ferumoxytol infusion and any MRI examinations2 (Table 1).
Indeed, ferumoxytol is a peculiar iron product that consists of small superparamagnetic iron oxide particles and is also used as an magnetic resonance contrast agent3; infusion in healthy volunteers has also been shown to significantly increase the R2* signal in hematopoietic bone marrow for up to 3 months and in liver for up to 6 months.4,5
Harman and colleagues extensively cited our recently published article6 that relates to MRI investigation of iron overload in hemodialysis patients, induced by intravenous iron sucrose (licensed as Venofer), another iron product extensively used worldwide but having strikingly different pharmacokinetic behavior from ferumoxytol. Indeed, well-conducted positron emission tomography (PET) studies both in minipigs and in humans with anemia (most of whom had renal failure) showed rapid radioactivity uptake by the liver, spleen, and bone marrow during the first 20 to 60 minutes following labeled iron-sucrose infusion, followed by a decrease in liver and spleen radioactivity after 6 hours7,8 (Table 1). Thus, a washout period of at least 7 days between the last iron-sucrose infusion and MRI, as proposed in our study, seems sufficient to avoid interference with this latter iron product.6
Iron polymaltose (also called ferric carboxymaltose), a more recent iron product licensed in the United States as Injectafer and in Europe as Ferinject, has also been studied by PET in patients with anemia, some of whom had renal failure. This latter study showed rapid radioactivity uptake in the liver, spleen, and bone marrow during the first 25 minutes after iron polymaltose infusion, followed by a rapid decrease in liver and spleen after 8 hours as well as major recycling of this iron product by bone marrow.9 Although the label states that Injectafer/Ferinject is not a contrast agent and does not interfere with MRI, its seems advisable, given the results of this PET scan study, to respect a 7-day washout period between Injectafer/Ferinject infusion and MRI10 (Table 1).
Finally, human PET and MRI interference data are lacking for low-molecular-weight iron dextran (licensed in the United States as INFeD and in Europe as Cosmofer/Ferrisat), an iron product taken up very rapidly by liver and spleen then released to bone marrow.11 Its blood half-life is 20 hours, and complete elimination takes about 4 days11 (Table 1). Thus, a washout period of about a month between INFed/Cosmofer infusion and MRI seems advisable. Data on other pharmaceutical intravenous iron products are given in Table 1.
During the past 2 decades, routine use of recombinant erythropoiesis-stimulating agents (ESAs) has enabled anemia to be corrected in dialysis patients, thereby improving their quality of life and permitting better outcomes. As successful use of ESA requires sufficient available iron, almost all end-stage renal disease patients on ESA now receive concomitant parenteral iron therapy. Radiologists must be aware that iron overload among dialysis patients is now an increasingly recognized clinical situation in the ESA era, yet was previously considered rare.6 Moreover, the KDIGO Controversies Conference on Iron Management in Chronic Kidney Disease, which took place in San Francisco on March 27 to 30, 2014 (and was attended by nephrologists, hematologists, hepatologists, and specialists in iron metabolism), recognized the entity of iron overload in hemodialysis patients and called for an agenda of research on this topic, especially by means of MRI.12
It is therefore very likely that radiologists will be heavily solicited in the future by nephrology teams requesting quantitative hepatic MRI in dialysis patients, both for research purposes and for diagnosis and follow-up of iron overload. Radiologists should be aware of the marked differences in the pharmacological properties of available intravenous iron products and their potential interference with MRI. Specific MRI protocols need to be established in radiology divisions for each pharmaceutical iron product, especially for treated dialysis patients.
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12. Kalantar-Zadeh K. Iron overload in CKD and affects on various tissues. Presented at: KDIGO Controversies Conference on Iron Management in Chronic Kidney Disease, March 27–30, 2014, San Francisco, California.