Role of angiotensin II in the development of nephropathy and podocytopathy of diabetes.
Role of angiotensin II in the development of nephropathy and podocytopathy of diabetes.
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DOI：
10.2174/157339911794273973
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发表时间：
2011-01
影响因子：
3.3
通讯作者：
Mundel P
中科院分区：
文献类型：
--
作者：
Campbell KN;Raij L;Mundel P
糖尿病肾病是全世界终末期肾病的主要原因。足细胞是高度分化的周细胞样细胞，对于肾过滤器的正常功能至关重要。足细胞的丧失是包括糖尿病肾病在内的进行性肾脏疾病的标志。足细胞是血管紧张素 II 介导的足细胞蛋白表达和分布改变所致损伤的直接靶标。此外，血管紧张素 II 通过增加钙流入和活性氧的产生来间接促进足细胞损伤。尽管血管紧张素 II 阻断作为一种治疗方式具有令人信服的理由，但尽管广泛使用血管紧张素转换酶抑制剂 (ACEI) 和血管紧张素受体阻断剂 (ARB)，但与糖尿病相关的终末期肾病的发病率仍在稳步增加。最近发表的临床试验重新引发了关于肾素-血管紧张素系统（RAS）双重阻断的安全性和有效性的争论。本综述总结了阻断血管紧张素 II 作为治疗糖尿病肾病的治疗靶点的基本原理，包括足细胞所发挥的关键作用。讨论了最近关于 RAS 阻断在治疗糖尿病肾病中的作用的相关临床试验。
Diabetic kidney disease is the leading cause of end-stage renal disease worldwide. Podocytes are highly differentiated, pericyte-like cells that are essential for normal function of the kidney filter. Loss of podocytes is a hallmark of progressive kidney diseases including diabetic nephropathy. Podocytes are a direct target for angiotensin II –mediated injury by altered expression and distribution of podocyte proteins. Additionally, angiotensin II promotes podocyte injury indirectly by increasing calcium influx and production of reactive oxygen species. Notwithstanding the convincing rationale for angiotensin II blockade as a treatment modality, the incidence of diabetes-related end stage renal disease has increased steadily despite widespread use of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Recently published clinical trials have rekindled a debate on the safety and efficacy of dual blockade of the renin-angiotensin system (RAS). This review summarizes the rationale for blockade of angiotensin II as a therapeutic target in treating diabetic kidney disease, including the critical role played by podocytes. Recent relevant clinical trials on the role of RAS blockade in the treatment of diabetic kidney disease are discussed.