Peroxisome proliferator-activated receptors in kidney diseases: A promising therapeutic target

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. • PPARs regulate metabolism, inflammation, oxidative stress, and fibrosis in kidney diseases. • PPAR isoforms show strong context- and cell-specific actions across renal pathologies. • PPAR-targeted therapies show promise, but safety issues demand more selective approaches.