Dual blockade of the renin-angiotensin system in diabetic nephropathy - A randomized double-blind crossover study

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 oft'he renin-an-iotensin system (PAS). 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 IS 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 beta -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 [890-1,9981). 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.