Navis G, Faber H J, de Zeeuw D, de Jong P E
Groningen Institute for Drug Studies (GIDS), Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Drug Saf. 1996 Sep;15(3):200-11. doi: 10.2165/00002018-199615030-00005.
ACE inhibitors effectively reduce systemic vascular resistance in patients with hypertension, heart failure or chronic renal disease. This antihypertensive efficacy probably accounts for an important part of their long term renoprotective effects in patients with diabetic and non-diabetic renal disease. The renal mechanisms underlying the renal adverse effects of ACE inhibitors--intrarenal efferent vasodilation with a consequent fall in filtration pressure--are held to be involved in their renoprotective effects as well. The fall in filtration pressure presumably contributes to the antiproteinuric effect as well as to long term renoprotection. The former is suggested by the positive correlation between the fall in filtration fraction and the reduction in proteinuria found during ACE inhibition. The latter is suggested by the correlation between the (slight) reduction in glomerular filtration rate at onset of therapy and a more favourable course of renal function in the long term. Such a fall in filtration rate at the onset of ACE inhibitor treatment is reversible after withdrawal, and can be considered the trade-off for long term renal protection in patients with diabetic and nondiabetic chronic renal disease. In conditions in which glomerular filtration is critically dependent on angiotensin II-mediated efferent vascular tone (such as a post-stenotic kidney, or patients with heart failure and severe depletion of circulating volume), ACE inhibition can induce acute renal failure, which is reversible after withdrawal of the drug. Systemic and renal haemodynamic effects of ACE inhibition, both beneficial and adverse, are potentiated by sodium depletion. Consequently, sodium repletion contributes to the restoration of renal function in patients with ACE inhibitor-induced acute renal failure. Our the other hand, co-treatment with diuretics and sodium restriction can improve therapeutic efficacy in patients in whom the therapeutic response of blood pressure or proteinuria is insufficient. Patients at the greatest risk for renal adverse effects (those with heart failure, diabetes mellitus and/or chronic renal failure) also can expect the greatest benefit. Therefore, ACE inhibitors should not be withheld in these patients, but dosages should be carefully titrated, with monitoring of renal function and serum potassium levels.
血管紧张素转换酶(ACE)抑制剂可有效降低高血压、心力衰竭或慢性肾病患者的全身血管阻力。这种降压功效可能是其对糖尿病和非糖尿病肾病患者长期肾脏保护作用的重要组成部分。ACE抑制剂的肾脏不良反应(肾内出球小动脉扩张,进而导致滤过压下降)背后的肾脏机制也被认为与其肾脏保护作用有关。滤过压下降可能有助于减少蛋白尿以及长期的肾脏保护。滤过分数下降与ACE抑制期间蛋白尿减少之间的正相关表明了前者。治疗开始时肾小球滤过率(轻微)下降与长期更有利的肾功能进程之间的相关性表明了后者。ACE抑制剂治疗开始时的这种滤过率下降在停药后是可逆的,可被视为糖尿病和非糖尿病慢性肾病患者长期肾脏保护的权衡。在肾小球滤过严重依赖血管紧张素II介导的出球小动脉张力的情况下(如肾动脉狭窄后肾脏,或心力衰竭和循环血容量严重减少的患者),ACE抑制可诱发急性肾衰竭,停药后可逆。ACE抑制的全身和肾脏血流动力学效应,无论是有益的还是有害的,都会因钠缺乏而增强。因此,补充钠有助于ACE抑制剂所致急性肾衰竭患者肾功能的恢复。另一方面,对于血压或蛋白尿治疗反应不足的患者,联合使用利尿剂和限制钠摄入可提高治疗效果。发生肾脏不良反应风险最高的患者(心力衰竭、糖尿病和/或慢性肾衰竭患者)也有望获得最大益处。因此,不应在这些患者中停用ACE抑制剂,但应仔细调整剂量,并监测肾功能和血钾水平。