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Abstract: PO0212

Cardiorenal Effects of the American College of Radiology (ACR) Group II Agent Gadobutrol (Dotarem): Renal Proximal Tubular Mitochondrial Toxicity and Acute Tubular Damage

Session Information

  • AKI Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    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
  • Escobar, G. Patricia, 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
  • Deaguero, Joshua, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States

Group or Team Name

  • Kidney Institute of New Mexico
Background

Patients are concerned about gadolinium (Gd) deposition from magnetic resonance contrast agents. Gd is the known cause of iatrogenic ‘nephrogenic’ systemic fibrosis and long-term gadolinium retention in every organ. Without prospective evidence, the ACR partitions brands of Gd-based contrast agents (GBCAs) into three groups: I, associated with the greatest number of systemic fibrosis cases; II, associated with few, if any, unconfounded cases of iatrogenic systemic fibrosis; and III, data are limited.

Methods

Male and female mice were randomized to GBCA treatment with an increasingly popular, ACR group II macrocyclic agent (Dotarem, 2.5 mmol/kg intraperitoneally, 20 doses over 4 weeks). Echocardiographic parameters were compared at the endpoint, tissues examined with transmission electron microscopy.

Results

Gd reduced cardiac systolic volume (29 ± 6 vs 34 ± 4 µL, mean ± SD, M-mode), increased fractional shortening (30 ± 4 vs 25 ± 2%, M-mode), and increased ejection fraction (57 ± 5 vs 50 ± 4%, M-mode). Renal tissue was characterized by tubular damage, pathologic lipid vacuolization, and diffuse mitochondrial toxicity (Figure).

Conclusion

GBCA treatment leads to diffuse and long-term intracellular retention in every vital (and non-vital) organ. These studies demonstrate that the American College of Radiology group II agents are far from clinically inert. Consistent with the first element of the Nuremberg Code, voluntary consent for GBCA administration should be obtained from every patient.

Figure. Systemic Gd treatment induced lipid-laden vacuoles with electron-dense material and pathologic mitochondrial changes. Transmission electron microscopy, renal proximal tubule.

Funding

  • NIDDK Support