Pirfenidone is a renal protective drug: Mechanisms, signalling pathways, and preclinical evidence

Abstract Renal fibrosis, a characteristic of all chronic kidney diseases, lacks effective therapeutic drugs currently. Pirfenidone (PFD), a small molecule drug with good oral bioavailability, is widely used in idiopathic pulmonary fibrosis and exerts anti-fibrotic, anti-inflammatory, antioxidant, and anti-apoptotic effects. These effects have been attributed to the suppression of cell growth factors (in particular, but not exclusively, transforming growth factor-β), matrix metalloproteinases, and the epithelial–mesenchymal transition, as well as the possible down-regulation of pro-inflammatory mediators (such as tumour necrosis factor-α), the protection of mitochondrial function, and the regulation of inflammatory cells. Considering the activation of similar anti-fibrotic pathways in lung and kidney disease and the broad activity of PFD, this drug has improved the treatment of the renal fibrotic disease. In this review, we briefly summarise the pharmacokinetics and safety of PFD as well as the mechanisms of PFD focusing on kidney disease. We summarise the effects of PFD on renal function and pathological alterations based on animal experiments, as well as changes in growth factors based on both animal and renal cell experiments. Moreover, given the activation of similar profibrotic pathways in pulmonary diseases and other disorders, we reviewed in-depth the possible signalling pathways targeted by PFD to attenuate renal fibrosis and protect renal function. Finally, we provide an overview of the current clinical trials of PFD for the treatment of renal fibrosis.