Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jacobsen
Peter
P
Steno Diabetes Center, Gentofte, Denmark. pkjacobsen@dadlnet.dk
Andersen
Steen
S
Rossing
Kasper
K
Jensen
Berit R
BR
Parving
Hans-Henrik
HH
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; D000077405:Irbesartan