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

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 approximately 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.