benazepril and Uremia

The administration of an angiotensin-converting enzyme (ACE) inhibitor or an oral adsorbent, AST-120 (Kremezin), prevents the progression of renal failure. This study was designed to determine the additional effects of AST-120 combined with an ACE inhibitor, benazepril, on the progression of renal fibrosis in uremic rats.. 5/6-nephrectomized uremic rats were divided into control uremic rats (CRF group), benazepril-treated uremic rats (CRF+B group) and uremic rats receiving benazepril and AST-120 (CRF+BK group). After 14 weeks of treatment renal function and pathological changes were investigated.. The progression of renal dysfunction was delayed in both the CRF+B and CRF+BK groups as compared with the CRF group. In the CRF+BK group, the level of serum and urinary indoxyl sulfate and the tubular accumulation of indoxyl sulfate decreased. Both the CRF+B and CRF+BK groups showed lower glomerular sclerosis indices than the CRF group. In the CRF+BK group, but not the CRF+B group, the interstitial fibrosis area and the expression of transforming growth factor (TGF) beta1 and tissue inhibitor of metalloproteinases (TIMP) 1 were decreased as compared with the CRF group. Furthermore, the CRF+BK group showed a smaller interstitial fibrosis area and a lower renal osteopontin expression than the CRF+B group.. Combination therapy of benazepril and AST-120 is more effective than benazepril alone in retarding the progression of interstitial fibrosis by reducing the expression of TGF-beta 1, TIMP-1 and osteopontin.

Topics: Adsorption; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Carbon; Cells, Cultured; Disease Progression; Drug Therapy, Combination; Fibroblasts; Fibrosis; Humans; In Situ Hybridization; Indican; Kidney; Kidney Diseases; Male; Nephrectomy; Nephrosclerosis; Osteopontin; Oxides; Rats; Rats, Sprague-Dawley; Sialoglycoproteins; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta; Transforming Growth Factor beta1; Uremia

This study tested whether the angiotensin-converting enzyme inhibitor (ACEI) benazepril can improve the insulin resistance and glucose tolerance in uremia. Fifteen uremic hypertensive patients were treated with benazepril in a dose of 10-20 mg per day for ten weeks, and ten healthy subjects, matched in age, sex ratio and body mass index (BMI), served as the control group. Before and after the treatment, an oral 75 g glucose tolerance test (OGTT) and insulin release test (IRT) were performed in two groups above, and the blood glucose and serum insulin concentrations at 0, 60, 120 and 180 minutes after glucose load were examined, and the insulin glycoregulatory activity, including insulin sensitivity index (ISI), glucose uptake rate (M), total areas under the glucose and insulin curves during OGTTs (AUCG AUCINS), was calculated. The changes of serum potassium and renal function before and after treatment were observed. It showed that (1) benazepril could reduce blood pressure significantly (SBP decreased from 174.8 +/- 12.0 mmHg to 151.5 +/- 9.0 mmHg, p <0.001; DBP decreased from 108.0 +/- 8.2 mmHg to 95.3 +/- 9.0 mmHg, p <0.001). The total response rate was 86.7%. (2) After treatment with benazepril for ten weeks, the blood glucose and serum insulin concentrations after glucose load and AUCG, AUCINS values in the uremic patients were significantly lower than before treatment, but were still significantly higher than in the controls. The values of ISI and M in the uremic patients after treatment were much higher than before treatment, but were still significantly lower than in the control subjects. (3) The differences of serum potassium and creatinine levels before and after treatment were not significant. These findings indicate that benazepril can not only reduce blood pressure effectively and safely, but also partly improve insulin resistance, hyperinsulinemia and glucose intolerance in uremia.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Case-Control Studies; Female; Glucose Intolerance; Humans; Hyperinsulinism; Hypertension, Renal; Insulin Resistance; Male; Middle Aged; Treatment Outcome; Uremia