A subdepressor low dose of ramipril lowers urinary protein excretion without increasing plasma potassium

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.