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Abstract: TH-PO848

High-Fat Diet Increases Gadolinium Retention in Mice

Session Information

Category: Health Maintenance‚ Nutrition‚ and Metabolism

  • 1400 Health Maintenance‚ Nutrition‚ and Metabolism

Authors

  • Wagner, Brent, New Mexico VA Health Care System, 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
  • Ali, Abdul Mehdi S., University of New Mexico Department of Earth & Planetary Sciences, Albuquerque, New Mexico, United States
  • Dokladny, Karol, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States

Group or Team Name

  • Kidney Institute of New Mexico
Background

Gadolinium is a heavy/rare earth (lanthanoid) metal extensively used in modern diagnostic medicine as an enhancer of magnetic resonance imaging (MRI) procedures. Exposure to gadolinium-based contrast agents can cause ‘nephrogenic’ systemic fibrosis (NSF), a medical condition characterized by skin fibrosis associated with severe pain, burning, and itching leading to inhibition or loss of joint flexibility and movement. Our team has shown that gadolinium is detectable in symptomatic and asymptomatic patients in the urine, hair, and nails after MRI contrast exposure. We have also pioneered mechanistic studies showing that C-C chemokine receptor 2-dependent activated myeloid cells and fibroblasts mediates NSF. It has been shown that the kidney is a reservoir for gadolinium-based contrast even days after a single dose. However, relative gadolinium retention in obese animals has not been examined.

Methods

Mice were randomized to a 60 kcal% fat diet (n=14) ad libitum (20 kcal% protein and 20 kcal% carbohydrates; Research Diets, Inc; D12492i) or control chow (19% protein, carbohydrates 47%, and fat 6.5 %; Tekland Diets; 2020x; n=8) for 18-20 weeks. Then, the groups were sub-divided into untreated (n=8) and gadolinium-based contrast agent-treated (Omniscan 2.5 mM) (n=14) subgroups 5 days a week for 4 weeks. Tissues were excised and snap-frozen in liquid nitrogen. On average, 15 mg of tissue were digested and gadolinium concentrations were quantified using PerkinElmer NexION 300D Inductively Coupled Plasma Mass Spectrometry (ICP/MS) with a detection limit of 0.01 ppb.

Results

We observed gadolinium retention in the kidney and liver of animals exposed to Omniscan. Interestingly, HFD increased gadolinium accumulation in tested organs in males and females. Similarly, tungsten retention was increased in animals (regardless of sex) treated with gadolinium. HFD exacerbated gadolinium retention. In the kidneys of males, Ca and P retention was augmented by HFD regardless of Omniscan treatment. Zn accumulation was not influenced by either Omniscan or HFD treatment.

Conclusion

Our data indicate that obesity promotes gadolinium retention in the kidney and liver. Future studies are needed to delineate the cellular mechanisms leading to augmented gadolinium accumulation in obese animals and demonstrate associated pathological consequences.

Funding

  • NIDDK Support