Exploring the Therapeutic Role of Pregnane X Receptor Activation in Acute Kidney Injury: Mechanisms and Clinical Implications.

Acute Kidney Injury (AKI) is a critical condition characterized by a rapid decline in kidney function, often resulting from ischemia-reperfusion, nephrotoxicity, or inflammation. Current treatments primarily rely on renal replacement therapies, which remain limited and controversial. The pregnane X receptor (PXR), a nuclear receptor involved in drug metabolism, immune regulation, and cellular homeostasis, has emerged as a promising target for AKI therapy. Preclinical studies suggest that PXR activation demonstrates protective effects in AKI through multiple mechanisms, including reducing inflammation, oxidative stress, and mitochondrial dysfunction. Specifically, PXR modulates nuclear factor-κB (NF-κB) signaling, supports mitochondrial function, regulates apoptosis, and enhances renal hemodynamics, thus mitigating AKI progression. Furthermore, PXR's role in the gut-liver-kidney axis strengthens intestinal barrier integrity and bile acid homeostasis, contributing to renal protection. Recent advances in research on the PXR agonists rifampicin and tanshinone IIA (TanIIA) highlight the potential of PXR-targeted therapies to mitigate nephrotoxicity and promote kidney recovery. This review provides a comprehensive analysis of PXR's protective mechanisms in AKI, underscoring its therapeutic potential and paving the way for new treatment strategies.