ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO092

Detecting the Metabolism of Gadolinium-Based Contrast Agents Using Electron Paramagnetic Resonance (EPR) Spectroscopy

Session Information

  • AKI: Mechanisms - I
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Wagner, Brent, New Mexico VA Health Care System, Albuquerque, New Mexico, United States
  • Hong, Emily, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Yang, Jing, University of New Mexico Department of Chemistry and Chemical Biology, Albuquerque, New Mexico, United States
  • Dokladny, Karol, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Deaguero, Joshua, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Escobar, G. Patricia, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States

Group or Team Name

  • Kidney Institute of New Mexico
Background

Magnetic resonance imaging (MRI) contrast agents cause kidney injury, symptoms associated with gadolinium (Gd) exposure (SAGE), and 'nephrogenic' systemic fibrosis. Contrast agents are mutlidentate complexes designed to chelate Gd to 1) reduce free ion toxicity and 2) enhance renal elimination. Whether liberation of Gd from these complexes is a mechanistic step of disease has yet to be proven.

Methods

Mice were administered MRI contrast agent as per routine in our laboratory. Room temperature solution EPR spectroscopy was performed using a Bruker EMX spectromert with associated Bruker magnetic control electronics and microwave bridges. The microwave frequency was ∼9.4 GHz, field attenuation 20-25 dB, modulation amplitudes 6 - 10G, 3.17×105 gain, and up to 16 scans.

Results

The g values for Dotarem (macocylic) and Omniscan (open-chained) were 1.9791 ± 0.0025 (mean, S.D.) and 1.9374 ± 0.0040, respectively.The g values for Omniscan and Dotarem did not change significantly regardless of freezing/thawing. Concentrated HCl altered the EPR spectra of gadolnium-based contrast agent regardless of class. The EPR spectra remained unchanged in mouse urine days after last administration.

Conclusion

The healthcare system largely disinherits individuals with gadolinium-induced complications, many of whom seek off-label therapies such as metal chelation. The affinities of proprietary chelates for gadolinium will not govern equilibrium (chelate-bound metal) as gadolinium precipitates into insoluble minerals according to Le Chatelier's principle. These discoveries provide the foundation for developing rational therapies and improving the safety of magnetic resonance imaging contrast agents.

EPR spectra of Dotarem and urine from a single gadolinium-treated mouse.

Funding

  • NIDDK Support