Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy; Nephrology and Dialysis Unit, Meyer Children's University Hospital, Florence, Italy; Excellence Center DENOTHE, University of Florence, Florence, Italy.
Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy; Excellence Center DENOTHE, University of Florence, Florence, Italy.
Matrix Biol. 2018 Aug;68-69:333-354. doi: 10.1016/j.matbio.2018.02.017. Epub 2018 Apr 11.
Renal fibrosis is a condition characterized by excessive extracellular matrix accumulation in the kidney. Representing the final common result of a variety of injuries, it can lead to chronic kidney disease and end-stage renal disease. Although major efforts have been made in understanding the process of renal fibrosis, attempts to halt its progression have been successful only in a laboratory setting with limited success in clinical practice. Here, we review the current knowledge on the process of renal fibrogenesis and the emerging anti-fibrotic drugs that have shown encouraging results in experimental models and were subsequently tested in clinical trials. We also propose possible explanations that may account for clinical trial failures and poor translation outcomes. Finally, we discuss alternative therapeutic options and future directions in which anti-fibrotic treatments may be coupled with drugs that can enhance endogenous tissue regeneration.
肾纤维化是一种以肾脏中细胞外基质过度积累为特征的疾病。它代表了多种损伤的最终共同结果,可导致慢性肾脏病和终末期肾病。尽管在理解肾纤维化过程方面做出了重大努力,但在实验室环境中仅取得了有限的成功,尝试阻止其进展的努力在临床实践中仅取得了有限的成功。在这里,我们回顾了肾纤维化过程的现有知识,以及在实验模型中显示出可喜结果并随后在临床试验中进行测试的新兴抗纤维化药物。我们还提出了可能的解释,这些解释可能是临床试验失败和转化结果不佳的原因。最后,我们讨论了替代治疗选择和未来的方向,其中抗纤维化治疗可能与可增强内源性组织再生的药物结合使用。