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Effect of iron administration on the aortic iron content and vascular calcification in phosphorus-loaded chronic

Masa Nakanishi1, Ayako Goto1, Takahide Iwasaki2

  • 1Division of Kidney, Dialysis and Cardiology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, 663-8501, Hyogo, Japan.

BMC Nephrology
|December 15, 2023
PubMed

Insights

Iron administration in chronic kidney disease (CKD) increased aortic iron but did not worsen vascular calcification (VC). Nrf2 pathway activation correlated with iron levels, suggesting a role in oxidative stress response in CKD patients.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Cardiovascular disease (CVD) is a leading cause of death in chronic kidney disease (CKD) patients, potentially linked to oxidative stress.
  • Vascular calcification (VC) is a key risk factor for accelerated CVD in CKD.
  • Phosphorus (Pi), iron (Fe), and Nrf2 are critical modulators of VC and oxidative stress in CKD.

Purpose of the Study:

  • To investigate the impact of iron (Fe) administration on aortic iron overload and vascular calcification (VC) in a rat model of CKD.
  • To determine the involvement of Nrf2 and its related genes (ferritin H, HIF-1α) in the development of VC following Fe administration.

Main Methods:

  • A CKD rat model was established using adenine and a high-Pi diet.
  • CKD rats received oral or intraperitoneal Fe administration.
  • Aortic Fe, calcium (Ca), and Pi content, along with Nrf2, ferritin H, HIF-1α, HMOX1, and NQO1 mRNA levels, were analyzed.

Main Results:

  • Intraperitoneal Fe administration significantly increased aortic Fe content, correlating with liver hepcidin (HAMP) mRNA levels.
  • Fe administration did not significantly alter aortic calcium (Ca) or phosphorus (Pi) content.
  • Aortic Nrf2 mRNA levels increased with Fe administration, correlating with aortic Fe, serum Pi, and mRNA levels of ferritin H, HIF-1α, HMOX1, and NQO1.

Conclusions:

  • Parenteral Fe administration elevates aortic Fe and liver HAMP mRNA but does not exacerbate VC in CKD rats.
  • Aortic Nrf2 mRNA levels are significantly correlated with aortic Fe and serum Pi, indicating a role in the oxidative stress response.
  • The Nrf2 pathway, along with ferritin H and HIF-1α, appears involved in the response to Fe loading and oxidative stress in CKD.
Abstract

Keywords:
Chronic Kidney DiseaseFerritin HHIF-1αNrf2PhosphorusVascular calcificationiron

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