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肾纤维化的治疗——将挑战转化为机遇

Treatment of Renal Fibrosis-Turning Challenges into Opportunities.

作者信息

Klinkhammer Barbara M, Goldschmeding Roel, Floege Jürgen, Boor Peter

机构信息

Institute of Pathology, RWTH University of Aachen, Aachen, Germany; Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands; and Division of Nephrology, RWTH University of Aachen, Aachen, Germany.

Institute of Pathology, RWTH University of Aachen, Aachen, Germany; Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands; and Division of Nephrology, RWTH University of Aachen, Aachen, Germany.

出版信息

Adv Chronic Kidney Dis. 2017 Mar;24(2):117-129. doi: 10.1053/j.ackd.2016.11.002.

Abstract

Current treatment modalities are not effective in halting the progression of most CKD. Renal fibrosis is a pathological process common to all CKD and thereby represents an excellent treatment target. A large number of molecular pathways involved in renal fibrosis were identified in preclinical studies, some of them being similar among different organs and some with available drugs in various phases of clinical testing. Yet only few clinical trials with antifibrotic drugs are being conducted in CKD patients. Here we review those clinical trials, focusing on agents with direct antifibrotic effects, with particular focus on pirfenidone and neutralizing antibodies directed against profibrotic growth factors and cell connection proteins. We discuss the potential reasons for the poor translation in treatment of renal fibrosis and propose possible approaches and future developments to improve it, eg, patient selection and companion diagnostics, specific and sensitive biomarkers as novel end points for clinical trials, and drug-targeting and theranostics.

摘要

目前的治疗方式在阻止大多数慢性肾脏病(CKD)进展方面并不有效。肾纤维化是所有CKD共有的病理过程,因此是一个理想的治疗靶点。临床前研究确定了大量参与肾纤维化的分子途径,其中一些在不同器官中相似,一些有处于不同临床试验阶段的可用药物。然而,仅有少数针对CKD患者的抗纤维化药物临床试验正在进行。在此,我们回顾这些临床试验,重点关注具有直接抗纤维化作用的药物,尤其关注吡非尼酮以及针对促纤维化生长因子和细胞连接蛋白的中和抗体。我们讨论肾纤维化治疗中转化效果不佳的潜在原因,并提出可能的方法和未来发展方向以改善这种情况,例如患者选择和伴随诊断、作为临床试验新终点的特异性和敏感性生物标志物,以及药物靶向和治疗诊断学。

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