Rayner Brian
Division of Nephrology, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
Curr Med Res Opin. 2004 Mar;20(3):333-40. doi: 10.1185/030079903125003107.
Diabetic nephropathy is the leading cause of end stage renal disease (ESRD), and given that treating this condition is a considerable economic burden, the prevention of ESRD is a major public health goal. The renin-angiotensin system (RAS) is aberrantly activated in patients with diabetes. Angiotensin II (AII), a downstream effector of the RAS, has haemodynamic and non-haemodynamic effects that contribute to the development and progression of nephropathy. For patients with type 2 diabetes mellitus (T2DM) and hypertension, an AII receptor blocker (AIIRB) is recommended as the first drug that should be used. This review will focus on the rationale for the use of losartan as a treatment for nephropathy associated with T2DM. In animal models of diabetes, losartan reduced proteinuria and conferred renal protection. In RENAAL (Reduction in Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan), the first major randomised trial that investigated the benefit of losartan in patients with T2DM and nephropathy, losartan significantly reduced the risk of a doubling of serum creatinine and progression to ESRD, significantly lowered the levels of proteinuria and slowed the rate of decline in glomerular filtration rate. This review also discusses other clinical trials of losartan and other AIIRBs in T2DM, and considers alternative mechanisms by which losartan may be exerting its effects. The collective experience in treatment trials highlighted in this review indicate that losartan and other AIIRBs can reduce blood pressure and the progression of proteinuria in diabetic renal disease. However, losartan is thus far the only AIIRB that has been shown to reduce significantly the risk of ESRD and cardiovascular events in patients with T2DM. Its use in hypertensive patients with T2DM and nephropathy may play an important role in reducing the burden of ERSD.
糖尿病肾病是终末期肾病（ESRD）的主要病因，鉴于治疗该疾病会带来相当大的经济负担，预防ESRD是一项主要的公共卫生目标。糖尿病患者的肾素-血管紧张素系统（RAS）被异常激活。血管紧张素II（AII）是RAS的下游效应物，具有血流动力学和非血流动力学效应，这些效应会促进肾病的发生和发展。对于2型糖尿病（T2DM）和高血压患者，推荐使用AII受体阻滞剂（AIIRB）作为首选药物。本综述将聚焦于使用氯沙坦治疗T2DM相关肾病的理论依据。在糖尿病动物模型中，氯沙坦可减少蛋白尿并提供肾脏保护。在RENAAL（非胰岛素依赖型糖尿病患者使用血管紧张素II拮抗剂氯沙坦降低终点事件）研究中，这是首个调查氯沙坦对T2DM和肾病患者益处的大型随机试验，氯沙坦显著降低了血清肌酐翻倍和进展至ESRD的风险，显著降低了蛋白尿水平，并减缓了肾小球滤过率的下降速度。本综述还讨论了氯沙坦和其他AIIRB在T2DM中的其他临床试验，并考虑了氯沙坦发挥作用的其他潜在机制。本综述中强调的治疗试验的总体经验表明，氯沙坦和其他AIIRB可降低糖尿病肾病患者的血压和蛋白尿进展。然而，氯沙坦是迄今为止唯一被证明能显著降低T2DM患者ESRD风险和心血管事件的AIIRB。在T2DM和肾病的高血压患者中使用氯沙坦可能在减轻ESRD负担方面发挥重要作用。
