Optimal Dose of Candesartan for Renoprotection in Type 2 Diabetic Patients With Nephropathy

Abstract

OBJECTIVE—We evaluated the optimal dose of the angiotensin II receptor antagonist candesartan cilexetil for renoprotection as reflected by short-term changes in albuminuria in hypertensive type 2 diabetic patients with nephropathy.

RESEARCH DESIGN AND METHODS—A total of 23 hypertensive patients with type 2 diabetes and nephropathy were enrolled in this double-blind randomized cross-over trial with four treatment periods, each lasting 2 months. Each patient received placebo and candesartan: 8, 16, and 32 mg daily in random order. Antihypertensive medication was discontinued before enrollment, except for long-acting furosemide, which all patients received throughout the study in median (range) doses of 40 (30–160) mg daily. End points were albuminuria (turbidimetry), 24-h blood pressure (BP) (Takeda-TM2420), and glomerular filtration rate (GFR) (⁵¹Cr-labeled EDTA plasma clearance technique).

RESULTS—Values obtained during placebo treatment: albuminuria [geometric mean (95% CI)] 700 (486–1,007) mg/24-h, 24-h BP (mean ± SE) 147 ± 4/78 ± 2 mmHg, and GFR 84 ± 6 ml/min/1.73 m². All three doses of candesartan significantly reduced albuminuria and 24-h BP compared with placebo. Mean (95% CI) reductions in albuminuria were 33% (21–43), 59% (52–65), and 52% (44–59) with increasing doses of candesartan. Albuminuria was reduced significantly more by the two highest doses than by the lowest dose (P < 0.01); 24-h systolic BP was reduced by 9 (2–16), 9 (2–16), and 13 (6–20) mmHg and 24-h diastolic BP was reduced by 5 (2–8), 4 (1–7), and 6 (3–9) mmHg with increasing doses of candesartan. There were no significant differences in the reductions in BP between the three doses. GFR was decreased by ∼6 ml/min/1.73 m² by all three doses of candesartan (P < 0.05 versus placebo).

CONCLUSIONS—The optimal dose of candesartan is 16 mg daily for renoprotection, as reflected by short-term reduction in albuminuria, in hypertensive type 2 diabetic patients with nephropathy.