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HIF Activation Against CVD in CKD: Novel Treatment Opportunities

Tetsuhiro Tanaka1, Kai-Uwe Eckardt2

  • 1Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.

Seminars in Nephrology
|May 14, 2018
PubMed

Insights

Prolyl hydroxylase (PHD) inhibitors stabilize hypoxia-inducible factors (HIFs), offering potential cardiovascular benefits for chronic kidney disease (CKD) patients. Careful evaluation is needed due to potential side effects of HIF activation.

Area of Science:

  • Nephrology
  • Cardiology
  • Biochemistry

Background:

  • Cardiovascular disease (CVD) is a major complication in chronic kidney disease (CKD).
  • Insufficient tissue oxygenation is linked to CVD in CKD patients.
  • Cellular oxygen sensing involves prolyl hydroxylases (PHDs) regulating hypoxia-inducible factors (HIFs).

Purpose of the Study:

  • To explore the potential cardiovascular benefits of PHD inhibitors in CKD.
  • To investigate the impact of HIF stabilization on CKD-related cardiovascular complications.

Main Methods:

  • Review of preclinical studies on PHD inhibitors and HIF activation.
  • Analysis of potential mechanisms for cardiovascular protection.
  • Consideration of potential adverse effects.

Main Results:

  • PHD inhibitors are in clinical trials for anemia in CKD.
  • Preclinical data suggest HIF activation may benefit myocardial infarction, cardiac remodeling, atherosclerosis, and peripheral artery disease.
  • HIF activation may improve glucose/lipid metabolism and lower blood pressure.

Conclusions:

  • PHD inhibitors show promise for treating CKD-related cardiovascular issues.
  • Potential benefits include improved cardiac function and metabolic parameters.
  • Careful assessment of HIF activation's net systemic effects is crucial for clinical application.

Keywords:
CKDCVDHIFPHD inhibitor

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