delapril and Albuminuria

Patients with diabetes complicated by hypertension and microalbuminuria have elevated cardiovascular risk, and controlling blood pressure in these patients is an urgent clinical priority. The present study aimed to examine the effects of a fixed-dose combination of antihypertensives on blood pressure and microalbuminuria.. Patients with type 2 diabetes, mild-to-moderate hypertension (diastolic blood pressure 85-105 mmHg, systolic blood pressure <160 mmHg, and 24-hour mean systolic blood pressure >130 mmHg), and microalbuminuria were randomized to 1 year of doubleblind treatment with fixed-dose manidipine/delapril (n=54) or losartan/hydrochlorothiazide (HCTZ) (n=56).. Blood pressure was significantly reduced at 1 year in both groups (-22.2/-14.6 mmHg and -19.5/-14.3 mmHg, for systolic and diastolic blood pressure respectively, P<0.001 for each), with no significant between-group difference. Reductions in microalbuminuria occurred in both groups, with mean changes at 1 year of -3.9 mg/mmol creatinine (95% CI -5.3, -2.5) for manidipine/delapril (P<0.001 vs. baseline) and -2.7 mg/mmol creatinine (95% CI -4.0, -1.3) for losartan/HCTZ (P<0.001 vs. baseline and P=0.199 between groups). Glycemia over the 1-year study was largely unaffected; the blood glucose concentration was reduced from baseline with manidipine/delapril, although not statistically significant (mean change -0.2 mmol/L, P=0.064). Both treatments were well tolerated, with discontinuation for adverse events for one (1.9%) patient in the manidipine/delapril group and two (3.6%) in the losartan/HCTZ group.. A fixed-dose manidipine/delapril combination represents a useful addition to the treatment options available to control hypertension complicated by diabetes and microalbuminuria.

Topics: Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Dihydropyridines; Double-Blind Method; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Indans; Losartan; Male; Middle Aged; Nitrobenzenes; Piperazines

This study was designed to investigate the effect of delapril, an ACE inhibitor, and manidipine, a long action calcium antagonist, on persistent microalbuminuria in normotensive type 2 diabetic patients. Sixty type 2 diabetic patients were randomized to take delapril 30 mg/day or manidipine 10 mg/day for 48 weeks, in an open label design. Twenty eight of thirty subjects in the delapril group and twenty nine of thirty in the manidipine group completed the study. Urine albumin excretion as measured by the urinary albumin creatinine ratio decreased significantly in both groups (112.0+/-60.9 to 95.3+/-64.9 mg/g and 108.5+/-51.0 to 96.4+/-53.5 mg/g in the delapril and manidipine group respectively, p < 0.05, by paired t-test). Systolic and diastolic blood pressure were not significantly changed after treatment in the delapril group but significantly decreased in the manidipine group (130.9+/-7.1/80.2+/-6.1 to 127.2+/-7.1/78.0+/-5.3 mm/Hg, p < 0.05, by student's paired t-test). After 48 weeks of treatment, two patients in the delapril group and one patient in the manidipine group converted to normoalbuminuria (urinary albumin:creatinine ratio < 30 mg/g) and one patient in each group progressed to overt nephropathy (urinary albumin:creatinine ratio > 300 mg/g). There were no significant changes in fasting plasma glucose, HbA1c, serum fructosamine, creatinine, potassium and lipid profiles after 48 weeks of treatment in both groups. Two cases in the delapril group were withdrawn during the study because of an intolerable cough and one case in the manidipine group because of intolerable dizziness and headache. In conclusion, both delapril and manidipine are effective in the reduction of microalbuminuria in normotensive type 2 diabetic patients with persistent microalbuminuria.

Topics: Adult; Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Diabetic Nephropathies; Dihydropyridines; Humans; Indans; Kidney; Middle Aged; Nitrobenzenes; Piperazines

The pathophysiological role of angiotensin II in the development of renal sclerosis was investigated in 5/6-nephrectomized, 12-week-old male spontaneously hypertensive rats. After 1 week of a control period, nephrectomized rats received one of the following treatments for 4 weeks: the selective nonpeptide angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme inhibitor delapril (30 mg/kg per day), hydralazine (15 mg/kg per day), or vehicle. Urinary protein and albumin excretions and systolic blood pressure were determined every week. Rats with reduced renal mass treated with vehicle had a poor survival rate (30%). Although TCV-116, delapril, and hydralazine treatment significantly improved the survival rate for 4 weeks, hydralazine failed to improve proteinuria and albuminuria as well as the decline in renal function compared with delapril or TCV-116. Histological examination revealed that both TCV-116 and delapril protected glomeruli from sclerosis, whereas hydralazine did not improve histological findings (5%, 7%, and 30% of glomeruli were affected, respectively). These results indicate that angiotensin II plays a dominant role through its type 1 receptor in the pathogenesis of renal deterioration by hypertension.

Topics: Albuminuria; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Chromatography, High Pressure Liquid; Hydralazine; Hypertension; Indans; Kidney; Male; Proteinuria; Rats; Rats, Inbred SHR; Survival Analysis; Tetrazoles