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Oxidative stress and NRF2 signaling in kidney injury

Cherry Ng1, Maxine Kim1, Yanti2

  • 1Department of Pharmacy and BK21FOUR Advanced Program for Smart Pharma Leaders, Graduate School of The Catholic University of Korea, Gyeonggi-do, 14662 Republic of Korea.

Toxicological Research
|February 27, 2025
PubMed

Insights

Targeting the NRF2 pathway shows promise for treating kidney diseases like acute kidney injury (AKI) and chronic kidney disease (CKD). Activating NRF2 (nuclear factor erythroid 2-related factor 2) can protect kidneys from damage and reduce fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathophysiology

Background:

  • Oxidative stress is a key factor in the development and progression of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD).
  • The nuclear factor erythroid 2-related factor 2 (NRF2) is a critical regulator of cellular antioxidant responses and redox homeostasis.
  • Dysregulation of NRF2 contributes to kidney damage in various pathological conditions.

Purpose of the Study:

  • To review the complex interplay between oxidative stress and kidney pathophysiology.
  • To explore the therapeutic potential of NRF2 activation in mitigating kidney damage and fibrosis.
  • To discuss the clinical implications and challenges of targeting NRF2 for kidney disorders.

Main Methods:

  • Review of existing literature on oxidative stress, NRF2, and kidney disease.
  • Analysis of data from preclinical models of AKI and CKD.
  • Examination of findings from clinical trials involving NRF2 activators.

Main Results:

  • Reduced NRF2 activity worsens kidney damage in AKI and CKD models.
  • NRF2 activation demonstrates renoprotective effects against various insults, including toxins, ischemia-reperfusion, and diabetic nephropathy.
  • NRF2 exerts anti-inflammatory and anti-fibrotic effects, partly through interaction with TGF-β signaling.

Conclusions:

  • NRF2 activation holds significant therapeutic potential for managing kidney diseases.
  • Modulating NRF2 activity in humans presents complexities, as evidenced by clinical trial outcomes.
  • Further research is essential to optimize NRF2-targeted therapies for renal disorders.
Keywords:
AKI-to-CKD transitionAcute kidney injuryChronic kidney diseaseNRF2Renal fibrosis

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