Keilani T, Danesh F R, Schlueter W A, Molteni A, Batlle D
Northwestern University Medical School, VA Chicago Health Care System, Lakeside Division, IL 60611, USA.
Am J Kidney Dis. 1999 Mar;33(3):450-7. doi: 10.1016/s0272-6386(99)70181-2.
Angiotensin-converting enzyme (ACE) inhibitors are increasingly administered to patients with chronic renal disease. One issue of concern with the use of ACE inhibitors in patients with impaired renal function is the possible development of hyperkalemia. We reasoned that the impact of ACE inhibitors on plasma potassium could be minimized by administering these agents at very low doses. To examine this issue, we investigated the effect of a low dose of ramipril (1.25 mg orally once daily) and an eight-fold higher dose (10 mg orally once daily) on plasma potassium in 13 patients with proteinuria and mild chronic renal insufficiency. The study was divided into four phases: placebo (4 weeks), low-dose ramipril (8 weeks), high-dose ramipril (8 weeks), and washout phase (4 weeks). With the low dose of ramipril, urinary protein excretion decreased significantly as early as after 1 week of administration (from 4.4 +/- 0.5 to 3.7 +/- 0.4 g/24 h; P < 0.025) and did not decrease any further thereafter even when the dose was increased eight-fold. Mean arterial blood pressure and plasma potassium did not change significantly with the low dose of ramipril, whereas with the higher dose, mean arterial blood pressure decreased significantly (from 107 +/- 2.0 to 100 +/- 2.0 mm Hg, P < 0.005), and plasma potassium increased significantly (from 4.53 to 4.78 mEq/L, P < 0.05). We conclude that a low dose of ramipril can reduce proteinuria to the same extent as an eight-fold higher dose without significantly lowering blood pressure or increasing plasma potassium. This latter feature may be advantageous for the treatment of patients at risk for hyperkalemia who require ACE inhibitors.
血管紧张素转换酶（ACE）抑制剂越来越多地应用于慢性肾病患者。在肾功能受损的患者中使用ACE抑制剂时，一个令人担忧的问题是可能会出现高钾血症。我们推测，通过以极低剂量给药这些药物，可以将ACE抑制剂对血钾的影响降至最低。为了研究这个问题，我们调查了低剂量雷米普利（每日口服1.25毫克一次）和高8倍剂量（每日口服10毫克一次）对13例蛋白尿和轻度慢性肾功能不全患者血钾的影响。该研究分为四个阶段：安慰剂阶段（4周）、低剂量雷米普利阶段（8周）、高剂量雷米普利阶段（8周）和洗脱阶段（4周）。使用低剂量雷米普利时，早在给药1周后尿蛋白排泄就显著减少（从4.4±0.5降至3.7±0.4克/24小时；P<0.025），此后即使剂量增加8倍也没有进一步减少。低剂量雷米普利时平均动脉血压和血钾没有显著变化，而高剂量时平均动脉血压显著降低（从107±2.0降至100±2.0毫米汞柱，P<0.005），血钾显著升高（从4.53升至4.78毫当量/升，P<0.05）。我们得出结论，低剂量雷米普利可以将蛋白尿减少到与高8倍剂量相同的程度，而不会显著降低血压或增加血钾。后一个特点对于需要ACE抑制剂的高钾血症风险患者的治疗可能是有利的。
