Brewster Ursula C, Perazella Mark A
Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8029, USA.
Am J Med. 2004 Feb 15;116(4):263-72. doi: 10.1016/j.amjmed.2003.09.034.
The renin-angiotensin-aldosterone system regulates renal vasomotor activity, maintains optimal salt and water homeostasis, and controls tissue growth in the kidney. However, pathologic consequences can result from overactivity of this cascade, involving it in the pathophysiology of kidney disease. An activated renin-angiotensin-aldosterone system promotes both systemic and glomerular capillary hypertension, which can induce hemodynamic injury to the vascular endothelium and glomerulus. In addition, direct profibrotic and proinflammatory actions of angiotensin II and aldosterone may also promote kidney damage. The majority of the untoward effects associated with angiotensin II appear to be mediated through its binding to the angiotensin II type 1 receptor. Aldosterone can also induce renal injury by binding to its receptor in the kidney. An understanding of this system is important to appreciate that inhibitors of this cascade can reduce the progression of chronic kidney disease in proteinuric disease states. Pharmacologic agents that can interfere with this cascade include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists. This paper will provide an overview of the renin-angiotensin system, review its role in kidney disease, examine the renal effects of inhibition of this cascade in experimental animal models, and review clinical studies utilizing renin-angiotensin-aldosterone inhibitors in patients with diabetic and nondiabetic nephropathies.
肾素-血管紧张素-醛固酮系统调节肾血管舒缩活动，维持最佳的盐和水平衡，并控制肾脏组织生长。然而，该级联反应过度活跃会导致病理后果，使其参与肾脏疾病的病理生理学过程。激活的肾素-血管紧张素-醛固酮系统会促进全身和肾小球毛细血管高血压，进而可导致对血管内皮和肾小球的血流动力学损伤。此外，血管紧张素II和醛固酮的直接促纤维化和促炎作用也可能促进肾脏损伤。与血管紧张素II相关的大多数不良影响似乎是通过其与1型血管紧张素II受体结合介导的。醛固酮也可通过与肾脏中的受体结合诱导肾损伤。了解该系统对于认识到该级联反应的抑制剂可减缓蛋白尿疾病状态下慢性肾脏病的进展很重要。可干扰该级联反应的药物包括血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂和醛固酮受体拮抗剂。本文将概述肾素-血管紧张素系统，综述其在肾脏疾病中的作用，研究在实验动物模型中抑制该级联反应的肾脏效应，并综述在糖尿病和非糖尿病肾病患者中使用肾素-血管紧张素-醛固酮抑制剂的临床研究。
