temocapril-hydrochloride and Hypertension--Renal

We conducted a multicenter, randomized, open-label, ascending dose study to investigate the efficacy and safety of combination therapy using the calcium channel blocker azelnidipine and angiotensin-converting enzyme (ACE) inhibitor temocapril in hypertensive diabetics. Patients received monotherapy with 8 mg azelnidipine (group A, n=112) or 2 mg temocapril (group T, n=111) for 4 weeks. If the target blood pressure (<130/80 mmHg) was not achieved, doses were doubled. If it was still not achieved, both drugs were coadministered at week 8, and, if needed, another antihypertensive drug was added after week 16. The treatment period was 52 weeks. Blood pressure was decreased significantly beginning at week 8 (p<0.0001 in both groups), and the systolic and diastolic blood pressure at the end of the treatment period was 128.2+/-11.1/76.4+/-8.1 mmHg. Overall, 53.8% (113/210) of patients achieved the target blood pressure by the end of the study. The effect during the monotherapy period (through week 8) was greater in group A than in group T (systolic, p=0.0475; diastolic, p=0.0001). Laboratory tests showed significant decreases in the urine albumin:creatinine ratio (p=0.0006), high-sensitivity C-reactive protein concentration (p=0.0073), and urine 8-isoprostane concentration (p=0.0215) at the end of the treatment period, as compared with baseline values. No adverse events caused safety problems. In conclusion, combination therapy using azelnidipine and temocapril is an effective treatment for hypertensive diabetics.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Azetidinecarboxylic Acid; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dihydropyridines; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension, Renal; Kidney Function Tests; Lipids; Male; Middle Aged; Thiazepines; Treatment Outcome

A 24-year-old Japanese woman with IgA nephropathy was admitted to our hospital due to the development of proteinuria and pretibial edema while on glucocorticoids and an angiotensin-converting-enzyme(ACE) inhibitor. She had been on both medications for more than 2 years. Urinary protein excretion was 2.53 g/day and renal function laboratory data were within the normal range. Plasma aldosterone concentration was high at 248 pg/ml, with normal plasma renin activity. The renal biopsy specimens showed prominent glomerular hypertrophy. Four weeks after the addition of valsartan, an angiotensin II receptor blocker(ARB), urinary protein excretion was remarkably reduced to 0.6 g/day without adversely affecting blood pressure. During the treatment period, proteinuria was maintained at less than 0.6 g/day and renal function remained normal. We propose that glomerular hypertension caused by insufficient suppression of the renin-angiotensin system was an essential factor underlying the increased urinary protein excretion in this patient. Combination therapy of an ARB and an ACE inhibitor appears to have a beneficial effect in patients with IgA nephropathy patients with persistent glomerular hypertension.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Humans; Hypertension, Renal; Renin-Angiotensin System; Tetrazoles; Thiazepines; Treatment Outcome; Valine; Valsartan