Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome
in diabetic patients. We tested whether dual blockade of the renin-angiotensin system
(RAS) with both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin
II receptor blocker (ARB) is superior to maximal recommended dose of ACE inhibitor
in type 1 diabetic patients with diabetic nephropathy (DN).
We performed a randomized, double-blind, crossover trial with 8 weeks treatment with
placebo and irbesartan 300 mg (once daily), added on top of enalapril 40 mg (once
daily). We included 24 type 1 patients with DN. At the end of each treatment period,
albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were measured.
Values on ACE inhibitors + placebo were: albuminuria [mean (95% CI)], 519 (342 to
789) mg/24 hours; blood pressure [mean (SEM)], 131 (3)/74 (1) mm Hg, and GFR [mean
(SEM)], 65 (5) mL/min/1.73 m2. Dual blockade of the RAS induced a reduction in albuminuria
[mean (95% CI)] of 25% (15, 34) (P < 0.001), a reduction in systolic blood pressure
of 8 mm Hg (4, 12) (P = 0.002), and a reduction of 4 mm Hg (2, 7) (P = 0.003) in diastolic
blood pressure. GFR and plasma potassium remained unchanged during both treatment
regimes. Dual blockade was safe and well tolerated.
Dual blockade of the RAS is superior to maximal recommended dose of ACE inhibitors
with regard to lowering of albuminuria and blood pressure in type 1 patients with
DN. Long-term trials are needed to further establish the role of dual blockade of
the RAS in renal and cardiovascular protection.