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Back to the Future: Glomerular Hyperfiltration and the Diabetic Kidney

机译:回到未来:肾小球超滤和糖尿病肾

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摘要

Observations that early changes in renal hemodynamics beget later kidney damage was a seminal scientific discovery that ultimately led to development of the only class of agents, inhibitors of the renin-angiotensin system (ACE inhibitors and angiotensin receptor blockers), approved by regulatory agencies for the treatment of diabetic kidney disease (DKD). The first drugs in this class were approved more than two decades ago, and the concept of glomerular hyperfiltration as a targetable mechanism for DKD goes back almost four decades. It is rather ironic that looking backward in this direction may move the field forward in the future. Despite tremendous efforts of the clinical and translational research community and enormous amounts of scientific evidence discovered about various disease mechanisms, no others have successfully translated to a new treatment for DKD. Processes like fibrosis and inflammation undoubtedly contribute in major ways to the pathogenesis of DKD, but many attempts to translate these mechanisms to therapeutic targets have not yet succeeded. This consequence is likely due to a number of issues in the design and conduct of clinical trials, lack of validated DKD biomarkers, and barriers in the regulatory and business domains(8).
机译:肾血流动力学的早期变化引起后来的肾脏损害的观察是一项开创性的科学发现,最终导致开发了唯一一类药物,即肾素-血管紧张素系统抑制剂(ACEI抑制剂和血管紧张素受体阻滞剂),并获得了监管机构的批准。治疗糖尿病肾病(DKD)。该类别中的首批药物已在二十多年前获得批准,并且肾小球超滤作为DKD的靶向机制的概念可以追溯到将近四十年。具有讽刺意味的是,朝这个方向往后看可能会在将来推动这一领域的发展。尽管临床和转化研究界做出了巨大的努力,并且发现了关于各种疾病机制的大量科学证据,但没有其他人成功地将其转化为DKD的新疗法。诸如纤维化和炎症之类的过程无疑会在DKD的发病机理中起主要作用,但许多将这些机制转化为治疗靶标的尝试尚未成功。这种结果可能是由于临床试验的设计和进行中的许多问题,缺乏经过验证的DKD生物标志物以及监管和业务领域的障碍所致(8)。

著录项

  • 来源
    《Diabetes》 |2017年第1期|14-16|共3页
  • 作者

    Katherine R. Tuttle;

  • 作者单位

    Providence Medical Research Center, Providence Health Care and Nephrology Division, Department of Medicine, Kidney Research Institute and Institute of Translational Health Sciences, University of Washington, Spokane, WA;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-18 03:46:06

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