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Kidney Week

Abstract: TH-PO091

Magnetic Resonance Imaging (MRI) Contrast Agent Safety: Speciating Intracellular Gadolinium-Rich Nanoparticles in Human and Rodent Kidneys

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, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Escobar, G. Patricia, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Deaguero, Joshua, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Dokladny, Karol, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Howard, Tamara A., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Degnan, James H., University of New Mexico Department of Mathematics and Statistics, Albuquerque, New Mexico, United States
  • Watt, John Daniel, Center for Integrated Nanotechnologies, Albuquerque, New Mexico, United States
  • Brearley, Adrian, University of New Mexico Department of Earth & Planetary Sciences, Albuquerque, New Mexico, United States

Group or Team Name

  • Kidney Institute of New Mexico
Background

The leitmotifs of MRI contrast agent-induced complications are kidney injury, symptoms associated with gadolinium (Gd) exposure (SAGE), Gd encephalopathy, and ‘nephrogenic’ systemic fibrosis. Despite evidence that Gd is retained intracellularly, disinherited patients flock to unproven therapies (e.g. chelation).

Methods

Patient kidneys (n = 5/5 contrast-exposed and naïve) were obtained from the University of New Mexico Health Sciences Center Human Tissue Repository. Inductively-coupled plasma mass spectroscopy was performed with a NexION 300D (PerkinElmer). Energy-dispersive x-ray spectoscopy was performed using a JEOL NEOARM 200 kV aberration correction scanning transmission electron microscope (human).

Results

Gd mineralized into nanoparticles throughout the renal cortex, particularly intralysomal in the proximal tubluar epithelia. By multivariable linear regression, gadolinium was positively correlated with phosphorus (P), oxygen (O), and magnesium (P < 0.001). Gd as a function of P and O was the optimal model based on Akaike information criterion (AIC) reduction.

Conclusion

Gd mineralizes intracellularly in kidneys. This has ramifications for all MRI contrast agents and purported SAGE therapies such as chelation.

Speciation of a gadolinium-rich nanoparticle in human kidney. A. Intracellular electron-dense material in kidney, including a glomerular podocyte (right). B. (Top) High magnification image of an electron density in patient tissue shown in A. (Bottom) 2-dimensional (2D) EDS spectral map for gadolinium (Gd), sulfur (S), calcium (Ca), chlorine (Cl), phosphorus (P), and iron (Fe). C. Energy-dispersive x-ray spectroscopic (EDS) line scan through the electron density in B (top).

Funding

  • NIDDK Support