Department of Nephrology, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Changchun, 130041, China.
Department of Nephrology, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Changchun, 130041, China.
Eur J Pharmacol. 2021 Nov 15;911:174503. doi: 10.1016/j.ejphar.2021.174503. Epub 2021 Sep 20.
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) 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 summarize the pharmacokinetics and safety of PFD as well as the mechanisms of PFD focusing on kidney disease. We summarize 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.
肾纤维化是所有慢性肾脏病的特征，目前缺乏有效的治疗药物。吡非尼酮（PFD）是一种具有良好口服生物利用度的小分子药物，广泛应用于特发性肺纤维化，并具有抗纤维化、抗炎、抗氧化和抗细胞凋亡作用。这些作用归因于对细胞生长因子（尤其是但不限于转化生长因子-β）和上皮-间充质转化的抑制，以及可能下调促炎介质（如肿瘤坏死因子-α）、保护线粒体功能和调节炎症细胞。鉴于肺和肾脏疾病中类似的抗纤维化途径的激活以及 PFD 的广泛活性，该药物改善了肾脏纤维化疾病的治疗。在这篇综述中，我们简要总结了 PFD 的药代动力学和安全性以及 PFD 针对肾脏疾病的作用机制。我们根据动物实验总结了 PFD 对肾功能和病理改变的影响，以及基于动物和肾小管细胞实验的生长因子变化。此外，鉴于肺部疾病和其他疾病中类似的促纤维化途径的激活，我们深入综述了 PFD 可能通过哪些信号通路来减轻肾纤维化和保护肾功能。最后，我们概述了 PFD 治疗肾纤维化的当前临床试验。
