Galle Jan
Department of Nephrology and Dialysis at Klinikum Lüdenscheid, Lüdenscheid, Germany.
Nat Clin Pract Cardiovasc Med. 2008 Jul;5 Suppl 1:S36-43. doi: 10.1038/ncpcardio0806.
Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT(1)) receptors at all stages of renovascular disease. Angiotensin receptor blockers (ARBs) that specifically block the AT(1) receptor offer the potential to prevent or delay progression to end-stage renal disease independently of reductions in blood pressure. Proteinuria--an early and sensitive marker for progressive renal dysfunction--is reduced by ARB use in patients with type 2 diabetic nephropathy and microalbuminuria or macroalbuminuria. Retrospective analysis of data available from early trials has confirmed this finding and has shown that albuminuria reduction is associated with lessening of cardiovascular risk. The ARB telmisartan is equivalent to enalapril in preventing glomerular filtration rate decline, and equivalent to valsartan in reducing proteinuria. Telmisartan is more effective than conventional therapy in lowering the risk of transition to overt nephropathy in hypertensive and normotensive patients. An additive effect has been seen in smaller studies when telmisartan has been added to lisinopril therapy, and high-dose telmisartan reduces albuminuria better than low-dose telmisartan. Similar data were obtained with other ARBs such as candesartan, losartan, valsartan, or irbesartan. These data support the proposition that blockade of the renin-angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection.
在肾血管疾病的各个阶段,肾素血管紧张素II 1型(AT(1))受体的激活引发了肾脏病理生理学变化。特异性阻断AT(1)受体的血管紧张素受体阻滞剂(ARB)具有独立于血压降低之外预防或延缓进展至终末期肾病的潜力。蛋白尿是进行性肾功能障碍的早期敏感标志物,在2型糖尿病肾病伴微量白蛋白尿或大量白蛋白尿的患者中,使用ARB可降低蛋白尿。对早期试验可得数据的回顾性分析证实了这一发现,并表明蛋白尿减少与心血管风险降低相关。ARB替米沙坦在预防肾小球滤过率下降方面与依那普利相当,在降低蛋白尿方面与缬沙坦相当。在高血压和血压正常的患者中,替米沙坦在降低进展为显性肾病的风险方面比传统治疗更有效。在较小规模的研究中,当替米沙坦添加到赖诺普利治疗中时可观察到相加效应,且高剂量替米沙坦比低剂量替米沙坦能更好地降低蛋白尿。使用其他ARB如坎地沙坦、氯沙坦、缬沙坦或厄贝沙坦也获得了类似数据。这些数据支持这样一种观点,即对肾素 - 血管紧张素系统的阻断程度超过最大程度降低血压所需的程度可提供最佳的肾脏保护。