Weinberg Marc S, Weinberg Adam J, Cord Raymond, Zappe Dion H
Division of Nephrology, Roger Williams Medical Center, Boston University School of Medicine Affiliate, Providence, RI 02904 USA,
Division of Nephrology, Roger Williams Medical Center, Boston University School of Medicine Affiliate, Providence, RI 02904 USA.
J Renin Angiotensin Aldosterone Syst. 2001 Mar;2(1_suppl):S196-S198. doi: 10.1177/14703203010020013401.
The optimal doses of angiotensin-converting enzyme inhibitors (ACE-I) and/or angiotensin II receptor blockers (ARBs) for maximal reduction in urinary protein excretion are not known. Moreover, beneficial effects from ARBs, such as tissue protection owing to a more complete blockade of the renin-angiotensin-aldosterone system (RAAS), may be independent of blood pressure-lowering by ARBs. In this investigation, we evaluated whether increasing the dose of candesartan cilexetil, in subjects already on the maximally-recommended FDA doses of 32 mg, would induce a further reduction in 24-hour urinary protein excretion in patients with heavy proteinuria (urinary protein excretion >1.5 g/day; mean 4.4±2 g/day). Ten patients were started on 16 or 32 mg of candesartan cilexetil daily. After 1-2 months of therapy, the dose was titrated upwards to 96 mg. In all subjects, there were further reductions in 24-hour urinary protein excretion when the dose was increased beyond the recommended 32 mg maximal dose. Increasing the dose of candesartan cilexetil to 96 mg was safe, as most subjects showed no changes in serum potassium and, as expected, only a slight increase (0.5-0.7 mg/dl) in serum creatinine. These data warrant further investigation, since some subjects may require higher doses of candesartan to achieve optimal regression of proteinuria.
目前尚不清楚血管紧张素转换酶抑制剂（ACE-I）和/或血管紧张素II受体阻滞剂（ARB）最大程度降低尿蛋白排泄的最佳剂量。此外，ARB的有益作用，如由于更完全阻断肾素-血管紧张素-醛固酮系统（RAAS）而产生的组织保护作用，可能独立于ARB的降压作用。在本研究中，我们评估了在已服用美国食品药品监督管理局（FDA）推荐最大剂量32mg坎地沙坦酯的受试者中，增加其剂量是否会进一步降低重度蛋白尿患者（尿蛋白排泄>1.5g/天；平均4.4±2g/天）的24小时尿蛋白排泄量。10名患者开始每日服用16mg或32mg坎地沙坦酯。治疗1-2个月后，剂量上调至96mg。在所有受试者中，当剂量增加超过推荐的最大剂量32mg时，24小时尿蛋白排泄量进一步降低。将坎地沙坦酯剂量增加至96mg是安全的，因为大多数受试者血清钾无变化，且正如预期的那样，血清肌酐仅轻微升高（0.5-0.7mg/dl）。这些数据值得进一步研究，因为一些受试者可能需要更高剂量的坎地沙坦以实现蛋白尿的最佳消退。
