Optimal dose of candesartan for renoprotection in type 2 diabetic patients with nephropathy: a double-blind randomized cross-over study.
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.


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.
Rossing
Kasper
K
Steno Diabetes Center, Gentofte, Denmark. Faculty of Health Science, University of Aarhus, Aarhus, Denmark.
Christensen
Per K
PK
Hansen
Birgitte V
BV
Carstensen
Bendix
B
Parving
Hans-Henrik
HH
D000368:Aged; D000419:Albuminuria / Q000188:drug therapy; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan