Candesartan Cilexetil, a Novel Angiotensin II Type 1 (AT1) Receptor Blocker, Reduces Microalbuminuria in Patients with Type II Diabetes Mellitus and Mild Hypertension

Abstract

Microalbuminuria is a predictor of nephropathy in patients with type I or type II diabetes mellitus, and interventions that decrease albuminuria are likely to postpone the development of severe renal impairment. Suppression of the renin-angiotensin system by angiotensin-converting enzyme (ACE) inhibition has been effective in this respect. However, direct inhibition of the negative cardiovascular effects of angiotensin II by means of an angiotensin II type 1 (AT 1 ) receptor blocker would be expected to produce reductions in albuminuria similar to those produced by ACE inhibition. In this study, we assessed the effect of candesartan cilexetil on microalbuminuria in patients with type II diabetes mellitus and mild hypertension. The analysis was performed in a subset of patients ( n = 35) with microalbuminuria (10-100 mg in an overnight urine sample) at randomization in a large double-blind, placebo-controlled study. The subset was part of a study investigating the effect of candesartan cilexetil on blood glucose homeostasis and the blood lipid profile in patients with stable type II diabetes mellitus, mild hypertension (diastolic blood pressure 90-100 mmHg) and serum creatinine levels below 150 &#55 mol/l for men and below 120 &#119 mol/l for women. Patients were randomized, after a 4-week placebo run-in period, to 12 weeks of double-blind treatment with candesartan cilexetil, 8-16 mg ( n = 83), or placebo ( n = 78) once daily. After 12 weeks of treatment, candesartan cilexetil did not influence blood glucose homeostasis or the blood lipid profile compared with placebo. Body weight remained unchanged in both treatment groups. Median urinary albumin excretion decreased by 57%, from 28.5 to 12.2 mg/12 h, in patients treated with candesartan cilexetil ( n = 15), whereas it increased by 9%, from 30.2 to 32.8 mg/12 h, in the placebo group ( n = 20; p = 0.03 for the difference between treatments). The mean reduction in diastolic blood pressure was 6.4 mmHg in the group given candesartan cilexetil and 3.6 mmHg in the group given placebo. In conclusion, 12 weeks of treatment with the AT 1 -receptor antagonist candesartan cilexetil reduced microalbuminuria in patients with stable type II diabetes mellitus and mild hypertension. Thus, candesartan cilexetil appears to have the potential for renal protection in this patient category.