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Kidney Week

Abstract: TH-PO1090

High-Fat Diet Amplifies Verapamil-Enhanced Gadolinium Retention in Bone, Kidney, and Liver After Magnetic Resonance Imaging Contrast Agent Exposure

Session Information

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Dokladny, Karol, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Escobar, G. Patricia, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Deaguero, Joshua, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Ali, Abdul Mehdi S., University of New Mexico, Albuquerque, New Mexico, United States
  • Howard, Tamara A., The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Brearley, Adrian, University of New Mexico, Albuquerque, New Mexico, United States
  • Saenz-Trevizo, Angelica, University of New Mexico, Albuquerque, New Mexico, United States
  • Henderson, Ian, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Wagner, Brent, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
Background

Diagnostic medicine relies heavily on gadolinium-based contrast agents in MRI scans. Gadolinium ions are highly toxic. Since 2006, gadolinium-based contrast agents have been linked to nephrogenic systemic fibrosis, a rare but progressive, highly disabling, and often fatal condition. Our rodent models have shown that experimental high-fat diets augment gadolinium retention and intracellular gadolinium-rich nanoparticle formation in multiple organs. The present study aimed to investigate whether Verapamil, a calcium channel blocker, modulates gadolinium retention in mice exposed to gadolinium-based contrast agents in the setting of dietary manipulation.

Methods

38 male C57BL/6 mice were randomized into two main groups: control (10 kcal% fat) and high-fat diet (60 kcal% fat). Each group was further subdivided into controls, Omniscan gadolinium-based contrast agent, Verapamil, a calcium channel blocker, and Omniscan and Verapamil. Omniscan (2 mM) and Verapamil (5 mg/kg) were injected intraperitoneally 5 days a week, for 4 weeks. After a 5-day washout, the kidneys, liver, heart, and bones were excised and snap-frozen in liquid nitrogen. On average, 15 mg of tissue was digested in nitric acid, and gadolinium levels were quantified using PerkinElmer NexION ICP-MS with a detection limit of 0.01 ppb.

Results

In all examined organs, exposure to Omniscan resulted in a significant gadolinium accumulation compared with saline-treated animals. The magnitude of gadolinium retention was organ dependent. In animals fed the control diet and exposed to Omniscan, the kidneys accumulated the highest concentration of gadolinium, followed by bone, liver, and heart. In the kidneys or liver of animals on a high-fat diet, exposure to Omniscan resulted in increased gadolinium retention. In the kidney, Verapamil augmented gadolinium accumulation in animals fed a chow diet. In the liver, Verapamil increased Gd retention regardless of diet. Zinc, calcium, and phosphorus levels were also determined.

Conclusion

Exposure to Omniscan results in organ-dependent gadolinium retention. A high-fat diet increases gadolinium retention in the kidney and liver of animals exposed to Omniscan. Verapamil affects gadolinium retention in an organ- and food-specific manner. Future studies are required to determine the mechanisms of Verapamil-induced changes in gadolinium accumulations.