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Abstract
The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal–ligand complexes, especially with repeated use, should be studied further.
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1 University of New Mexico Health Science Center, Kidney Institute of New Mexico, Albuquerque, USA (GRID:grid.266832.b) (ISNI:0000 0001 2188 8502); University of New Mexico Health Science Center, Albuquerque, USA (GRID:grid.266832.b) (ISNI:0000 0001 2188 8502); New Mexico Veterans Administration Health Care System, Albuquerque, USA (GRID:grid.266832.b)
2 University of New Mexico Health Science Center, Albuquerque, USA (GRID:grid.266832.b) (ISNI:0000 0001 2188 8502)
3 University of New Mexico, Department of Earth and Planetary Sciences, Albuquerque, USA (GRID:grid.266832.b) (ISNI:0000 0001 2188 8502)
4 University of New Mexico, Department of Mathematics and Statistics, Albuquerque, USA (GRID:grid.266832.b) (ISNI:0000 0001 2188 8502)
5 Chan Zuckerberg Initiative, Redwood City, USA (GRID:grid.507326.5) (ISNI:0000 0004 6090 4941)
6 Los Alamos National Laboratory, Center for Integrated Nanotechnologies, Los Alamos, USA (GRID:grid.148313.c) (ISNI:0000 0004 0428 3079)