Studies have shown that dual
therapy with
angiotensin-converting enzyme inhibitors (ACEI) and either
angiotensin II receptor blockers or
aldosterone receptor antagonists is more effective in reducing
proteinuria than either agent used alone. The questions that remain are as follows: (1) Which of these agents should be used as dual
therapy with the ACEI? (2) Does a higher level of blockade of the renin-angiotensin-aldosterone system with triple
therapy offer an advantage over dual blockade? A 3-mo randomized, double-blind, placebo-controlled study was performed in 41 patients with
proteinuria >1.5 g/d. Four treatment groups were compared: (1)
Ramipril +
spironolactone placebo +
irbesartan placebo, (2)
ramipril +
irbesartan +
spironolactone placebo, (3)
ramipril +
irbesartan placebo +
spironolactone, and (4)
ramipril +
irbesartan +
spironolactone. The percentage change in
protein excretion differed according to treatment arm (ANOVA: F(3,35) = 8.6, P < 0.001). Pair-wise comparison showed that greater reduction in
protein excretion occurred in treatment regimens that incorporated
spironolactone. The reduction in
proteinuria at 3 mo was as follows: Group 1, 1.4%; group 2, 15.7%; group 3, 42.0%; and group 4, 48.2%. The reduction in
proteinuria among patients who were taking
spironolactone-containing regimens was sustained at 6 and 12 mo. This study suggests that
aldosterone receptor blockade offers a valuable adjuvant treatment when used with ACEI
therapy for the reduction of
proteinuria. Results suggest no advantage of triple blockade over dual blockade of the renin-angiotensin-aldosterone system to reduce
proteinuria.