2004 Volume 47 Issue 12 Pages 921-929
Beneficial effects of combination therapy consisting of an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor antagonist (ARB) have increasingly been reported in patients with diabetic nephropathy, but few studies have been performed in Japan. In the present study 36 type 2 diabetes patients with incipient or overt nephropathy who had been treated with an ACEI for more than 6 months were randomly separated into 3 groups: a group in which an ARB was substituted for the ACEI (ARB group), a group in which an ARB was added to the ACEI (ACEI+ARB group), and a group in which the ACEI was continued (ACEI group). Candesartan (mean daily dose 5mg) was administered, and 24-hr urine was collected at home before and 6 months after entry into the study. Blood pressure did not differ between the groups throughout the study period. Urinary protein excretion significantly increased in the ACEI group (p<0.05), but no significant changes were observed in the other two groups. The percentage change in urinary protein excretion was significantly lower in the ACEI+ARB group than in the ACEI group (ACEI group, 119±52%;ARB group, 19±29%;ACEI+ARB group 9±17%, p<0.05vs ACEI group). There was no significant correlation between the changes in blood pressure and urinary protein excretion. Creatinine clearance significantly decreased in the ACEI group over 6 months (80±8ml/min at baseline vs 70±6ml/min 6 months later, p<0.05), but no significant changes were observed in the other two groups (ARB group, 87±11ml/min at baseline vs 84±7ml/min 6 months later, ns;ACEI+ARB group, 86±10ml/min at baseline vs 80±11ml/min 6 months later, ns). Serum uric acid significantly increased in the ACEI group, but the serum potassium and hemoglobin levels did not change in any of the groups. The results of this study suggest that combination therapy consisting of an ACEI and an ARB may retard the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.
