Department of Medicine, University of Virginia Health System, Charlottesville, USA.
Am J Nephrol. 2010;31(6):541-50. doi: 10.1159/000313363. Epub 2010 May 18.
The existence of local or tissue-based renin-angiotensin-aldosterone systems (RAAS) is well documented and has been implicated as a key player in the pathogenesis of cardiovascular and renal diseases. The kidney contains all elements of the RAAS, and intrarenal formation of angiotensin II not only controls glomerular hemodynamics and tubule sodium transport, but also activates a number of inflammatory and fibrotic pathways. Experimental and clinical studies have shown that the intrarenal RAAS is activated early in diabetic nephropathy, the leading cause of chronic kidney disease (CKD). Although angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the rate of decline in kidney function in patients with diabetic and non-diabetic nephropathy, many patients still progress to end-stage renal disease or die from cardiovascular events. There is still a clear need for additional strategies to block the RAAS more effectively to reduce progression of CKD. The focus of this paper is to review the importance of the intrarenal RAAS in CKD and recent findings in renin-angiotensin biology pertinent to the kidney. We also discuss additional strategies to inhibit the RAAS more effectively and the potential impact of direct renin inhibition on the prevention and management of CKD.
局部或组织肾素-血管紧张素-醛固酮系统（RAAS）的存在已得到充分证实，并被认为是心血管和肾脏疾病发病机制中的关键因素。肾脏包含 RAAS 的所有成分，肾内血管紧张素 II 的形成不仅控制肾小球血流动力学和肾小管钠转运，还激活许多炎症和纤维化途径。实验和临床研究表明，糖尿病肾病早期肾内 RAAS 就被激活，而糖尿病肾病是慢性肾脏病（CKD）的主要病因。尽管血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂可降低糖尿病和非糖尿病肾病患者肾功能下降的速度，但许多患者仍进展为终末期肾病或死于心血管事件。仍然需要更有效的阻断 RAAS 的额外策略来减少 CKD 的进展。本文的重点是回顾肾内 RAAS 在 CKD 中的重要性以及与肾脏相关的肾素-血管紧张素生物学的最新发现。我们还讨论了更有效地抑制 RAAS 的其他策略以及直接抑制肾素对预防和管理 CKD 的潜在影响。
