Dual Blockade of the Renin-Angiotensin System in Diabetic Nephropathy: A randomized double-blind crossover study (original) (raw)

OBJECTIVE—Many patients with diabetic nephropathy (DN) have levels of albuminuria >1 g/day and blood pressure >135/85 mmHg, despite antihypertensive combination therapy, including recommended doses of ACE inhibitors, e.g., lisinopril/enalapril at 20 mg daily. We tested the concept that such patients might benefit from dual blockade of the renin-angiotensin system (RAS).

RESEARCH DESIGN AND METHODS—We performed a randomized double-blind crossover study of 2 months treatment with candesartan cilexetil 8 mg once daily and placebo in addition to previous antihypertensive treatment. We included 18 type 2 diabetic patients with DN fulfilling the above-mentioned criteria. All received recommended doses of ACE inhibitor and, in addition, 15 patients received diuretics, 11 received a calcium channel antagonist, and 3 received a β-blocker. At the end of each treatment period, we measured the glomerular filtration rate (GFR), 24-h blood pressure, albuminuria, and IgGuria .

RESULTS—The addition of candesartan to usual antihypertensive therapy induced a mean (95% CI) reduction in albuminuria of 25% (2–58), P = 0.036 (geometric mean [95% CI] from 1,764 mg/24 h [1,225–2,540] to 1,334 mg/24 h [890–1,998]). It also produced a mean reduction of 35% (9–53) in the fractional clearance of albumin (P = 0.016), a reduction of 32% (1–54) in fractional clearance of IgG (P = 0.046), a reduction in 24-h systolic blood pressure of 10 mmHg (2–18) (P = 0.019) (mean ± ± SE) from 148 ± 3 to 138 ± 5 mmHg, and a mean reduction in GFR of 5 ml · min−1 · 1.73 m−2 (0.1–9) (P = 0.045).

CONCLUSIONS—Dual blockade of the RAS reduces albuminuria and blood pressure in type 2 diabetic patients with DN responding insufficiently to previous antihypertensive therapy, including ACE inhibitors in recommended doses.

Address correspondence and reprint requests to Kasper Rossing, Steno Diabetes Center, Niels Steensens Vej 2, Dk-2820 Gentofte, Denmark. E-mail: [email protected].

Received for publication 20 June 2001 and accepted in revised form 21 September 2001.

H.-H.P. has received honoraria or consulting fees from Merck, AstraZeneca, BMS, Sanofi-Synthelabo, and Pfizer, and he has received grant/research support from Merck and Sanofi-Synthelabo.

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