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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Transcription Factors as Therapeutic Targets in Chronic Kidney Disease
Akihito Hishikawa1, Kaori Hayashi2, Hiroshi Itoh3
1Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. a-hishikawa@keio.jp.
Abstract:
The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial. Recently, we have reported that the transcription factor Kruppel-like factor 4 (KLF4) regulates the glomerular podocyte epigenome, and that the antiproteinuric effect of the renin⁻angiotensin system blockade may be partially mediated by KLF4. KLF4 is one of the Yamanaka factors that induces iPS cells and is reported to be involved in epigenetic remodeling. In this article, we summarize the transcription factors associated with CKD and particularly focus on the possibility of transcription factors being novel drug targets for CKD through epigenetic modulation.
Insights
Transcription factors regulate kidney disease. Targeting these factors, like Nrf2 and KLF4, offers new therapeutic strategies for chronic kidney disease (CKD) via epigenetic modulation.
Area of Science:
- Nephrology
- Molecular Biology
- Epigenetics
Background:
- Chronic kidney disease (CKD) is a growing global health concern.
- Transcription factor (TF) deregulation is linked to kidney disease onset and progression.
Purpose of the Study:
- To review TFs implicated in CKD.
- To explore TFs as novel therapeutic targets for CKD, focusing on epigenetic modulation.
Main Methods:
- Literature review of studies on TFs in CKD.
- Analysis of clinical trials involving TF-targeting agents (e.g., Nrf2, HIF).
- Examination of KLF4's role in podocyte epigenome and kidney disease.
Main Results:
- Nrf2 activation shows potential for CKD regression.
- HIF stabilizers are under clinical trial for renal benefits.
- KLF4 regulates podocyte epigenetics and mediates renin-angiotensin system blockade effects.
Conclusions:
- Transcription factors are promising drug targets for CKD.
- Epigenetic modulation by TFs like KLF4 presents novel therapeutic avenues for kidney disease.
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