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Peroxisome proliferator-activated receptors in kidney diseases: A promising therapeutic target
Qiuyi Li1, Zhenwei Shi2, Xiujie Shi2
1National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Abstract:
Peroxisome proliferator-activated receptors (PPARs) play critical roles in metabolic regulation, inflammation, and cellular differentiation. Recent studies have revealed their significant involvement in a spectrum of kidney diseases, including chronic kidney disease (CKD), acute kidney injury (AKI), diabetic kidney disease (DKD), renal cell carcinoma, lupus nephritis, and autosomal dominant polycystic kidney disease. In this narrative review, we summarize current insights into the roles and mechanisms of PPARs in kidney pathophysiology and evaluate the efficacy of PPAR-targeted therapies in both animal models and clinical studies. Collectively, our analysis highlights the therapeutic potential of PPARs as promising molecular targets for renal disorders, particularly CKD, AKI, and DKD. However, important challenges remain for clinical translation, including dose-dependent adverse effects and the lack of renal-specific drug delivery, both of which highlight the need for safer and more targeted PPAR modulators.
Insights
Peroxisome proliferator-activated receptors (PPARs) are crucial for kidney health. PPAR-targeted therapies show promise for kidney diseases like CKD, AKI, and DKD, but require safer, more specific drug development.
Area of Science:
- Molecular biology
- Nephrology
- Pharmacology
Background:
- Peroxisome proliferator-activated receptors (PPARs) regulate key cellular processes including metabolism, inflammation, and differentiation.
- PPARs are implicated in the pathophysiology of various kidney diseases such as chronic kidney disease (CKD), acute kidney injury (AKI), and diabetic kidney disease (DKD).
Purpose of the Study:
- To review current knowledge on the roles and mechanisms of PPARs in kidney diseases.
- To evaluate the therapeutic efficacy of PPAR-targeting strategies in preclinical and clinical settings.
Main Methods:
- Narrative review of existing literature.
- Analysis of data from animal models and human clinical studies on PPAR modulators.
Main Results:
- PPARs play significant roles in the development and progression of diverse renal disorders.
- PPAR-targeted therapies demonstrate therapeutic potential, particularly for CKD, AKI, and DKD.
- Challenges include dose-dependent side effects and lack of renal specificity.
Conclusions:
- PPARs represent promising therapeutic targets for kidney diseases.
- Development of safer, renal-specific PPAR modulators is essential for clinical translation.
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