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In healthy individuals, serum creatinine levels remain stable due to a balance between its constant production—primarily from muscle metabolism—and renal excretion. Creatinine is freely filtered by the glomeruli, making it a valuable marker for estimating renal function. When the glomerular filtration rate (GFR) decreases, the kidneys can only eliminate less creatinine, causing serum levels to rise.Serum creatinine concentration is widely used to estimate creatinine clearance...
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Renal dysfunction significantly impairs the renal clearance of drugs, leading to potential complications in drug therapy. Renal failure, which can be caused by various factors, poses a significant challenge in the elimination of drugs from the body.
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Nox4 in renal diseases: An update.

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  • 1School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.

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NADPH oxidase 4 (Nox4) produces hydrogen peroxide (H2O2) in the kidney, impacting various renal diseases. Its role is complex and context-dependent, offering potential therapeutic targets.

Keywords:
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Area of Science:

  • Renal pathophysiology
  • Oxidative stress in kidney disease
  • Molecular mechanisms of renal injury

Background:

  • Reactive oxygen species (ROS) from NADPH oxidase are implicated in numerous kidney diseases.
  • Nox4 is the primary NADPH oxidase isoform in the kidney, generating H2O2 that influences physiological functions.
  • Nox4's involvement in redox processes is critical across conditions like diabetic nephropathy, AKI, and renal cell carcinoma.

Purpose of the Study:

  • To review the function and mechanisms of Nox4 in the context of renal diseases.
  • To highlight existing contradictions and controversies in the Nox4 literature.
  • To discuss potential therapeutic strategies targeting Nox4 for renal disease treatment.

Main Methods:

  • Literature review of studies investigating Nox4 in renal diseases.
  • Analysis of Nox4's role across various kidney cell types (epithelial, podocytes, mesangial, endothelial, fibroblasts).
  • Examination of factors contributing to Nox4's variable functional outcomes.

Main Results:

  • Nox4 exhibits dual roles, promoting cell survival in some contexts and inducing apoptosis, inflammation, or fibrogenesis in others.
  • Functional variability is linked to cell type, subcellular localization, concentration, and disease state.
  • Nox4 activates multiple signaling pathways contributing to renal pathology.

Conclusions:

  • The precise role of Nox4 in renal diseases is complex and often contradictory.
  • Understanding the context-specific functions of Nox4 is crucial for therapeutic development.
  • Targeting Nox4 presents a promising avenue for treating specific renal diseases.