Treatment of Renal Fibrosis-Turning Challenges into Opportunities
Treatment of Renal Fibrosis-Turning Challenges into Opportunities
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DOI：
10.1053/j.ackd.2016.11.002
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发表时间：
2017-03-01
影响因子：
2.9
通讯作者：
Boor, Peter
中科院分区：
文献类型：
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作者：
Klinkhammer, Barbara M.;Goldschmeding, Roel;Boor, Peter
目前的治疗方式不能有效阻止大多数CKD的进展。肾纤维化是所有CKD的共同病理过程，因此是一个很好的治疗靶点。在临床前研究中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，一些在临床试验的各个阶段具有可用药物。然而，只有少数抗纤维化药物的临床试验正在CKD患者中进行。在这里，我们回顾这些临床试验，重点是直接抗纤维化作用的药物，特别关注吡非尼酮和针对促纤维化生长因子和细胞连接蛋白的中和抗体。我们讨论了肾纤维化治疗中翻译不佳的潜在原因，并提出了可能的方法和未来的发展，以改善它，例如，患者选择和伴随诊断，特异性和敏感性生物标志物作为临床试验的新终点，以及药物靶向和治疗诊断学。(C)2016年，美国国家肾脏基金会（National Kidney Foundation，Inc.）All rights reserved.
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 excellenttreatment 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. (C) 2016 by the National Kidney Foundation, Inc. All rights reserved.