Barton Matthias
Molecular Internal Medicine, University of Zurich, LTK Y 44 G 22, Winterthurer Strasse 190, CH-8057 Zürich, Switzerland.
Biochim Biophys Acta. 2010 Dec;1802(12):1203-13. doi: 10.1016/j.bbadis.2010.03.012. Epub 2010 Mar 30.
Diabetes and arterial hypertension continue to be the main causes of chronic renal failure in 2010, with a rising prevalence in part due to the worldwide obesity epidemic. Proteinuria is a main feature of chronic renal disease and mediated by defects in the glomerular filtration barrier and is as a good predictor of cardiovascular events. Indeed, chronic renal disease due to glomerulosclerosis is one of the important risk factors for the development of coronary artery disease and stroke. Glomerulosclerosis develops in response to inflammatory activation and increased growth factor production. Preclinical and first preliminary clinical studies provide strong evidence that endogenous endothelin-1 (ET-1), a 21-amino-acid peptide with strong growth-promoting and vasoconstricting properties, plays a central role in the pathogenesis of proteinuria and glomerulosclerosis via activation of its ET(A) subtype receptor involving podocyte injury. These studies have not only shown that endothelin participates in the disease processes of hypertension and glomerulosclerosis but also that features of chronic renal disease such as proteinuria and glomerulosclerosis are reversible processes. Remarkably, the protective effects of endothelin receptors antagonists (ERAs) are present even on top of concomitant treatments with inhibitors of the renin-angiotensin system. This review discusses current evidence for a role of endothelin for proteinuric renal disease and podocyte injury in diabetes and arterial hypertension and reviews the current status of endothelin receptor antagonists as a potential new treatment option in renal medicine.
2010年，糖尿病和动脉高血压仍是慢性肾衰竭的主要病因，其患病率不断上升，部分原因是全球肥胖症流行。蛋白尿是慢性肾病的主要特征，由肾小球滤过屏障缺陷介导，是心血管事件的良好预测指标。事实上，由肾小球硬化引起的慢性肾病是冠心病和中风发生的重要危险因素之一。肾小球硬化是对炎症激活和生长因子产生增加的反应。临床前和初步临床研究提供了有力证据，表明内源性内皮素-1（ET-1），一种具有强大促生长和血管收缩特性的21个氨基酸的肽，通过激活其ET(A)亚型受体（涉及足细胞损伤）在蛋白尿和肾小球硬化的发病机制中起核心作用。这些研究不仅表明内皮素参与高血压和肾小球硬化的疾病过程，还表明蛋白尿和肾小球硬化等慢性肾病特征是可逆过程。值得注意的是，内皮素受体拮抗剂（ERAs）的保护作用即使在与肾素-血管紧张素系统抑制剂联合治疗时也存在。本综述讨论了内皮素在糖尿病和动脉高血压中对蛋白尿性肾病和足细胞损伤作用的现有证据，并综述了内皮素受体拮抗剂作为肾脏医学潜在新治疗选择的现状。
