Anguiano Lidia, Riera Marta, Pascual Julio, Soler María José
Department of Nephrology, Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), 88 Dr. Aiguader Street, Barcelona, 08003, Spain.
Red de Investigación Renal (REDINREN), Instituto Carlos III-FEDER, Madrid 28029, Spain.
J Clin Med. 2015 May 25;4(6):1171-92. doi: 10.3390/jcm4061171.
Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA) receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors (ETA and ETB) within the kidney, as well as the ET-1 functions through them. In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described.
糖尿病肾病（DKD）仍然是慢性肾病最常见的病因，人们已经评估了多种主要针对肾素-血管紧张素系统的治疗药物。它们在减缓疾病进展至终末期肾病方面仅具有部分疗效，这表明显然需要其他有效的治疗方法。在糖尿病背景下，内皮素-1（ET-1）主要通过激活其内皮素A（ETA）受体，参与血管收缩、肾损伤、系膜增殖、肾小球硬化、纤维化和炎症反应。因此，内皮素受体拮抗剂已被提议作为潜在的药物靶点。在DKD的实验模型中，内皮素受体拮抗剂已被证明可改善肾损伤和纤维化，而在DKD患者中的临床试验则显示出抗蛋白尿作用。目前，正在对其在长期临床试验中的肾脏保护作用进行测试。本综述重点关注内皮素受体（ETA和ETB）在肾脏中的定位，以及ET-1通过这些受体发挥的功能。此外，我们总结了内皮素受体拮抗剂在实验研究和人体研究中的治疗益处以及已报道的不良反应。
