[Long-term decrease of microalbuminuria after one year of treatment with perindopril in hypertensive diabetic...

We studied the effects of perindopril, an angiotensin converting enzyme (ACE) inhibitor administered during 12 months, on creatinine clearance, albuminuria and glycaemic control in diabetic subjects with mild to moderate hypertension. After 1 month placebo, 40 insulin-treated patients were divided into 3 groups based upon their urinary albumin excretion rate. Group 1 had a normoalbuminuria (less than 15 mg/24 h), group II had a microalbuminuria (15-150 mg/24 h) and group III had a macroproteinuria (greater than 150 mg/24 h and Albustix +). They were given perindopril 4 to 8 mg orally once daily, and received a stable diet. Diastolic blood pressure was normalized within the first 3 months in 80% of the patients. From these, 28 (14.7 and 7 from groups I, II and III respectively) were followed during a total active treatment period of 12 months. They were matched for age, duration of diabetes and hypertension, systolic and diastolic blood pressures, daily insulin dose, postprandial plasma C-peptide and quality of glycaemic control. Mean supine diastolic blood pressure was decreased by 15 and 18% at 1 and 12 months respectively. Heart rate was not significantly modified. At 3 months, plasma ACE activity was nearly totally inhibited while plasma renin activity was markedly increased. In patients of group II, microalbuminuria was reduced from 66 +/- 13 (mean +/- SEM after placebo) to 39 +/- 6 mg/24 h after 1 month perindopril and this effect was maintained at 12 months. In group I, albuminuria remained within the normal range. In group III, macroproteinuria was not consistently modified by perindopril. Creatinine clearance did not change and glycaemic control remained stable throughout the study in the 3 groups. No major side effects were observed. We conclude that perindopril normalizes blood pressure in a large majority of hypertensive diabetic patients without affecting the quality of diabetes control. It also induces a marked and sustained reduction of microalbuminuria in patients at risk of developing diabetic nephropathy.