T. Keilani et al., A subdepressor low dose of ramipril lowers urinary protein excretion without increasing plasma potassium, AM J KIDNEY, 33(3), 1999, pp. 450-457
Angiotensin-converting enzyme (ACE) inhibitors are increasingly administere
d 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 ve
ry low doses. To examine this issue, we investigated the effect of a low do
se of ramipril (1.25 mg orally once daily) and an eight-fold higher dose (1
0 mg orally once daily) on plasma potassium in 13 patients with proteinuria
and mild chronic renal insufficiency. The study was divided into four phas
es: placebo (4 weeks), low-dose ramipril (8 weeks), high-dose ramipril (8 w
eeks), and washout phase (4 weeks), With the low dose of ramipril, urinary
protein excretion decreased significantly as early as after 1 week of admin
istration (from 4.4 +/- 0.5 to 3.7 +/- 0.4 g/24 h; P < 0.025) and did not d
ecrease any further thereafter even when the dose was increased eight-fold.
Mean arterial blood pressure and plasma potassium did not change significa
ntly with the low dose of ramipril, whereas with the higher dose, mean arte
rial blood pressure decreased significantly (from 107 +/- 2.0 to 100 +/- 2.
0 mm Hg, P < 0.005), and plasma potassium increased significantly (from 4.5
3 to 4.78 mEq/L, P < 0.05). We conclude that a low dose of ramipril can red
uce proteinuria to the same extent as an eight-fold higher dose without sig
nificantly lowering blood pressure or increasing plasma potassium, This lat
ter feature may be advantageous for the treatment of patients at risk for h
yperkalemia who require ACE inhibitors. (C) 1999 by the National Kidney Fou
ndation, Inc.