benazepril and Glomerulonephritis

Stage 3 is the key phase of chronic kidney disease. Traditional Chinese medicine (TCM) has been used for the treatment of chronic kidney disease. But a large sample trial is desirable.. A total of 578 Chinese patients with primary glomerulonephritis in CKD stage 3 were randomly assigned to three groups: patients received TCM (TCM group), benazepril (Ben group), TCM combined with benazepril (TCM+Ben group). Patients were followed up for 24 weeks. The primary endpoint was the time to the composite of 50% increased of serum creatinine, end stage renal disease or death.. eGFR in the TCM and the TCM+Ben group were improved (week 24 vs. baseline, P<0.05) while eGFR in the Ben group was decreased (week 24 vs. baseline, P>0.05). 24h urinary protein excretion (UP) and urinary albumin/creatinine (UAlb/Cr) were decreased in the TCM+Ben (week 24 vs. baseline, P<0.05) and the Ben group (week 24 vs. baseline, P>0.05). UP and UAlb/Cr were increased in the TCM group to week 12, then were stable (week 24 vs. baseline, P<0.05). The hemoglobin in the TCM group was also improved (week 24 vs. baseline, P<0.05). The accumulative survival rate in the TCM+Ben group was higher than that in the TCM group and the Ben group (P=0.044). Side effects in the TCM group were the lowest in these groups (P<0.05). The patients with dry cough in the TCM+Ben group and the Ben group were increased as compared with the TCM group (P<0.05). Hyperkalemia happened less frequently in the TCM group as compared with the other two groups (P=0.052).. For the patients with CKD stage 3, TCM can improve eGFR and hemoglobin with lower side effects. Benazepril significantly decreased the proteinuria. Chinese medicine integrated with benazepril can ameliorate renal function and decrease proteinuria synergistically.

Topics: Adult; Albuminuria; Benzazepines; Cough; Creatinine; Double-Blind Method; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Glomerular Filtration Rate; Glomerulonephritis; Hemoglobins; Humans; Hyperkalemia; Kidney; Kidney Failure, Chronic; Male; Medicine, Chinese Traditional; Middle Aged; Phytotherapy; Proteinuria; Severity of Illness Index

Proteinuria and hypertension are predictors of poor renal outcome in chronic glomerulonephritis (CGN). At the same level of blood pressure (BP) control, we evaluated which is superior, dual blockade of the rennin-angiotensin system (RAS) with both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 (AT-1) receptor blockade (ARB) or single blockade of ARB to reduce proteinuria and to preserve renal function in patients with CGN.. In this prospective, parallel, open study of 86 patients with CGN, we compared the effects on proteinuria and renal functions of 36 months with comparable blood pressure (BP) control achieved by candesartan cilexetil (candesartan, 4-12 mg/day) or benazepril hydrochrolide (benazepril, 2.5-10 mg/day) with candesartan (4 mg/day). Aiming at BP 125/75 mmHg or less, the dose of candesartan (single blockade) or benazepril (dual blockade) was increased.. Dual blockade decreased proteinuria more than single blockade with ARB (-42.3 vs. -60.5%, P < 0.01). Renal plasma flow (RPF) and glomerular filtration fraction (GFR) did not change significantly in either group. The filtration fraction (FF) decreased dual blockade more than single blockade (-1.7 vs. -19.0%, P < 0.05). Decreased FF was associated with the reduction of proteinuria (P < 0.05). Six percent of patients with dual blockade were not able to continue the study because of a dry cough.. Long-term dual blockade decreased proteinuria more than single blockade with ARB. Although ARB and ACEI have a glomerular size-selective function for proteinuria, a greater antiproteinuric effect may depend on renal hemodynamics, especially FF. Increased levels of bradykinin after ACEI can decrease FF and ameliorate proteinuria. Dry cough is a significant adverse effect of ACE inhibitor.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Benzazepines; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Chronic Disease; Drug Therapy, Combination; Female; Glomerulonephritis; Humans; Kidney; Male; Middle Aged; Proteinuria; Renin-Angiotensin System; Tetrazoles

Evidence suggests that the effectiveness of angiotensin-converting enzyme (ACE) inhibition diminishes with time, resulting in increasing angiotensin II levels, the action of which can be inhibited by the addition of an angiotensin receptor blocker (ARB). In the present study, the renal protective effects of ACE inhibitors and ARBs were compared over a five-year period in a prospective, randomized, open-blind study in 68 nondiabetic Japanese patients with elevated serum creatinine levels.. Japanese patients with renal insufficiency were randomly assigned to receive either an ACE inhibitor (benazepril 1.25 to 5 mg daily or trandolapril 0.5 to 4 mg daily) or ARB (candesartan 2 to 8 mg daily or losartan 25 to 100 mg daily) at the Kidney Disease Center at Saitama Medical School Hospital. The primary study endpoint was a change in glomerular filtration rate (GFR) between the baseline value and the last available value obtained during the five-year treatment period, as estimated by the Cockcraft-Gault equation. Secondary endpoints included the annual changes in GFR, serum creatinine level, urinary protein excretion, and blood pressure, as well as the rate of development of endstage renal disease.. There were no significant differences in the primary endpoint between the two groups. However, after 4 years, the decline in GFR in patients treated with ARBs was significantly greater than that seen in patients treated with an ACE inhibitor (p<0.05). Furthermore, the rate of introduction of dialysis therapy was also significantly greater in the ARB-treated patients (52.7% in ACE inhibitor and 81.2% in ARB group at year 5. p<0.01).. While our data suggested that ARB, like ACE, treatment might slow the progression of renal dysfunction, it also pointed to the necessity to be alerted to the progression to endstage renal disease with longterm medication.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Chronic Disease; Creatinine; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Indoles; Losartan; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Tetrazoles

Treatment with agents interfering with the renin-angiotensin system retards the progressive course of proteinuric chronic renal disease. However, because of unwanted effects associated with such therapy, some patients cannot be treated with these drugs at all or may be administered only very small doses. To find an optimal nephroprotective strategy for these patients, we compared antiproteinuric effects of combination therapy with an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor antagonist in very small doses with treatment with either agent alone at greater, but not maximal, doses. We compared the concomitant use of benazepril, 5 mg, and losartan, 25 mg, and monotherapy with these agents in doses 2-fold greater.. This is a randomized, open, crossover study of 3 treatments in 3 periods of 4 months each. Twenty-four patients with primary glomerulonephritis and nonnephrotic proteinuria, recognized previously as not able to be administered high doses of drugs from these classes, completed the protocol.. Combined therapy decreased 24-hour proteinuria (-45.54% versus baseline) more effectively than either losartan (-28.17%; analysis of variance, P < 0.01) or benazepril (-20.19%; analysis of variance, P < 0.001) alone. Subgroup analysis showed that antiproteinuric effects of combination therapy, as well as losartan or benazepril alone, were significantly greater in patients with basal proteinuria greater than 2 g/24 h than in those with proteinuria less than this value (P < 0.001, P < 0.01, and P < 0.05, respectively). All therapies significantly decreased blood pressure (BP) compared with baseline, but there were no differences between treatments in BP changes.. The study shows that combination therapy with very small doses of losartan and benazepril was more effective in reducing proteinuria than greater doses of either agent in monotherapy, and this greater antiproteinuric efficacy was independent of changes in BP.

Topics: Adult; Angiotensin II Type 2 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Cross-Over Studies; Drug Therapy, Combination; Female; Glomerulonephritis; Humans; Losartan; Male; Prospective Studies; Proteinuria; Renin-Angiotensin System

Although post exercise proteinuria has long been known, its exact pathophysiology is unclear. Our objective was to determine whether long-term angiotensin converting enzyme (ACE) inhibition by different ACE inhibitors had an influence on post exercise proteinuria. We studied 14 patients who also had mild, chronic proteinuria caused by diabetes mellitus or chronic glomerulonephritis. We compared changes both in chronic (baseline) and post exercise proteinuria, during and after treatment with three different ACE inhibitors, with appropriate washout periods for the three drugs to all 14 patients. Proteinuria (mg/24 hours +/- SD), prior to the treatment was 682 +/- 92. Proteinuria after treatment for 30 days with benazepril was 464.4 +/- 82.6 (p < 0.001), with enalapril: 477.1 +/- 105.5 (p < 0.001), and captopril: 504.7 +/- 100.1 (p < 0.001). Proteinuria three days after discontinuing the treatment with benazepril was 532.4 +/- 113.5, (p < 0.01), with enalapril: 561.3 +/- 128.5, (p < 0.01), and with captopril: 620.8 +/- 101.8, p = n.s. Post exercise proteinuria prior to treatment (mg/min. +/- SD) was: 1.38 +/- 0.32, vs. after a 30-day treatment period with benazepril: 0.81 +/- 0.19 (p < 0.001), enalapril: 0.95 +/- 0.24, (p < 0.001), captopril: 1.09 +/- 0.27 (p < 0.02). Post exercise proteinuria three days after discontinuing the treatment was (blood pressure already back to baseline): in case of benazepril: 1.26 +/- 0.36 (p = n.s.), of enalapril: 1.17 +/- 0.46 (p = n.s.), and of captopril: 1.34 +/- 0.41 (p = n.s.). We conclude that the renin-angiotensin system plays a significant role in the pathogenesis of post exercise proteinuria; the antiproteinuric effect of ACE inhibition in exercise-induced proteinuria seems to be associated chiefly with the hemodynamic changes due to these drugs, whereas in chronic proteinuria the antiproteinuric and antihypertensive effects are, at least partially, dissociated.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Captopril; Chronic Disease; Diabetes Mellitus, Type 2; Enalapril; Exercise; Female; Glomerulonephritis; Humans; Male; Proteinuria

In this study we compared the antihypertensive and antiproteinuric efficacies of an angiotensin-converting enzyme inhibitor and of conventional treatment consisting of a beta blocker and a diuretic in 13 patients with biopsy-proven glomerulonephritis and a proteinuria of more than 2 g/24 h. Ten of these 13 patients were normotensive. None had diabetes mellitus. In a randomized cross-over design with two treatment periods of 6 weeks, each preceded by a washout period of 4 weeks, patients were treated with benazepril (20 mg o.d.) and the combination of metoprolol (200 mg o.d.) and chlorthalidone (25 mg o.d.). At the end of the treatment periods with benazepril or metoprolol/chlorthalidone mean arterial pressure was lowered to a similar degree by 7.4 (mean, 95% confidence interval 2.0-12.7) and 9.7 (5.7-13.7) mmHg respectively. Both treatment modalities caused similar reductions in proteinuria, being 3.4 g/24 h (mean, 95% confidence interval 2.1-4.8) on benazepril and 3.2 (1.2-5.1) g/24 h on metoprolol/chlorthalidone. Glomerular filtration rate and renal plasma flow were slightly less during metoprolol/chlorthalidone treatment. Subgroup analysis of normotensive patients gave similar results. In conclusion, in these patients with glomerular disease angiotensin-converting enzyme inhibition was not more effective than the conventional treatment with the combination of a beta blocker and a diuretic in reducing blood pressure and proteinuria. Both treatments reduced proteinuria not only in hypertensive, but also in normotensive patients.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Chlorthalidone; Drug Combinations; Female; Glomerulonephritis; Hemodynamics; Humans; Kidney; Male; Metoprolol; Middle Aged; Proteinuria

A double-blind, placebo-controlled study was carried out to assess the effects of a three-month treatment with a new ACE inhibitor, Benazepril (BNZ), on systemic and renal hemodynamics, and urine protein excretion, in 20 patients with chronic glomerulonephritis, normal blood pressure (130/83 +/- 16/10 mm Hg), and normal renal function (creatine clearance 106 +/- 25 ml/min). Treatments with placebo or BNZ were assigned randomly. A wide range of proteinuria lowering effect was observed in overall population (from 1 to 84%, average 34%). Following the arbitrary level of a 30% reduction, two well-matched subgroups (10 patients for each one) were obtained: "good responders" (average decrease 51%), and "poor responders" (average decrease 17%). The main distinctive feature between the two groups was a higher plasma renin activity level in good than in poor responders. A positive correlation between the fall in proteinuria and blood pressure was found. Although the decrease in blood pressure seems to represent the major factor in determining the reduction in proteinuria, a multiple correlation analysis showed that the most prominent role (71%) was attributable to the combined decrease in blood pressure and filtration fraction, and then also to the efferent arteriole dilatation. Our conclusion is that ACE inhibitors are capable of also reducing proteinuria in patients with renal disease with normal blood pressure, the effect being more pronounced in those exhibiting humoral, systemic and renal hemodynamic patterns, indicating a greater activity of circulating and renal renin angiotensin system.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Double-Blind Method; Female; Glomerulonephritis; Hemodynamics; Humans; Kidney; Male; Proteinuria; Randomized Controlled Trials as Topic; Renal Circulation; Time Factors

Topics: Benzazepines; Chronic Disease; Glomerulonephritis; Humans; Irbesartan

Topics: Adolescent; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Chronic Disease; Drug Therapy, Combination; Female; Glomerulonephritis; Humans; Male; Middle Aged; Proteinuria; Tetrazoles; Valine; Valsartan; Young Adult

It has been well demonstrated that angiotensin-converting enzyme inhibitors (ACEIs) can retard the progression of renal failure and kidney sclerosis in patients and animal models with glomerular diseases. The aim of this study was to observe the influences of ACEI on intrarenal Ang II and TGFbeta1 local formation and their relation to renal protective effects. Experimental glomerulosclerosis with nephrotic syndrome was induced in unilateral nephrectomized rats with repeated injections of adriamycin. Rats were randomly divided into three groups: 1) a sham-operated control group (n=8); 2) an NS group treated with ACEI (benazepril 4 mg/kg/d) (n=10), and 3) an NS group not treated (n=10). After 8 wk, serum, urine and renal tissue were collected for study. ACE activity and Ang II concentration in renal tissue were measured by colorimetry and radioimmunoassay, respectively. Immunohistochemistry staining was employed for transforming growth factor-beta1 (TGFbeta1) and extracellular matrix (ECM) examination. TGFbeta1 mRNA was assessed by in situ hybridization. Compared with those of non-treated nephropathy rats, ACE activity (13.39+/-5.02 vs. 49.13+/-12.92 U/ml, p< 0.01) and Ang II (402.61+/-80.22 vs. 751.63+/-137.45 pg/mg/pr p < 0.01) in renal tissue were significantly inhibited in the rats treated with ACEI. At the same time, proteinuria was significantly reduced (155.06+/-103.56 vs. 421.11+/-148.45 mg/24 h, p < 0.01) and renal function improved (Scr 76.3+/-33.1 vs. 107.1+/-71.0, p < 0.05), concomitant with a reduction in the glomerular sclerosis index (30.6+/-19.5 vs. 120.3+/-61.9, p < 0.01) and a reduction in ECM accumulation such as Col IV, III, LN and FN (29.2+/-9.8 vs. 76.8+/-12.4; 29.5+/-12.4 vs. 85.9+/-11.5; 26.0+/-5.1 vs. 69.6+/-1.73; 32.4+/-12.4 vs. 70.5+/-13.5; p< 0.01 in all cases). In the ACEI treated group, these histologic benefits coincided with a reduced expression of TGFbeta1 in both tubular cells and sclerosed glomeruli in protein as well as mRNA level. These findings provide further evidence that ACEI (benazepril) can prevent the progression of renal damage in both the function and morphologic changes which associated with a down-regulation of intrarenal Ang II level through the relative inhibition of renal ACE activity. The blocking of the intrarenal renin angiotensin system (RAS) might contribute to the inhibition of TGFbeta1 local formation and the TGFbeta1-mediated ECM accumulation that are related to the renal protective effects of ACEI.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Doxorubicin; Glomerulonephritis; Kidney; Male; Nephrectomy; Nephrotic Syndrome; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Transforming Growth Factor beta

To explore the possible mechanism of benazepril in diminishing the progression of the renal diseases.. Experimental glomerulosclerosis in rats was induced by adriamycin. The treated group was given benazepril (4 mg x kg(-1) x d(-1)). Intrarenal angiotensin converting enzyme (ACE) activity and angiotensin II (AngII) concentration were measured with colorimetry and radioimmunoassay respectively. Immunohistochemistry staining was employed for transforming growth factor beta1 (TGF beta1) and extracellular matrix (ECM) examination. To observe the expression of TGFbeta1 mRNA in the kidney, in situ hybridization was performed.. In the rats treated with benazeapril, ACE activity and Ang II concentration in renal tissue were significantly inhibited. In the meantime, expression of TGFbeta1 mRNA and TGFbeta1 protein were down-regulated, accompanied by decreasing accumulation of ECM (compared with the untreated rats, P < 0.01).. Benazepril plays an important role in down-regulating the expression of TGFbeta1 and decreasing the accumulation of ECM by blocking intrarenal renin-angiotensin system.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Doxorubicin; Extracellular Matrix Proteins; Glomerulonephritis; Kidney; Male; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1