benazepril and Kidney-Failure--Chronic

Cardiovascular (CV) disease, its associated risk factors and continued progression run in parallel with renal deterioration (cardio-renal syndrome). Most guidelines promote early treatment, including the use of ACE inhibitors to control CV risk in patients with chronic renal failure. The renoprotective effects of the ACE inhibitor, benazepril, independent of blood pressure control, have been demonstrated, as monotherapy or in combination with amlodipine or hydrochlorothiazide, in large clinical trials: Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) and Gauging Albuminuria Reduction with Lotrel in Diabetic Patients with Hypertension (GUARD) in patients with mild-to-severe chronic kidney disease. In the ACCOMPLISH trial, CV outcomes and renoprotective effects were greater in patients receiving benazepril in combination with amlodipine; the GUARD trial demonstrated that combined benazepril/hydrochlorothiazide was more effective than amlodipine combined with benazepril in reducing baseline urinary albumin:creatinine ratio and normalizing urinary albumin:creatinine ratio in patients with baseline microalbuminuria, although this effect was accompanied with a greater decrease in glomerular filtration rate than with benazepril/amlodipine. While this is not a study in patients with overt renal disease (patients had severe CV diseases), the ACCOMPLISH trial is the first large study to date to show the added benefit of combining ACE inhibitors and calcium-channel blockers in renal protection. Future large, well-controlled trials, designed to evaluate hard renal outcomes, are required to identify which patients will benefit most from particular combination treatment strategies in renoprotection.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Hypertension; Kidney Failure, Chronic; Risk Factors

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

The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6 mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Biomarkers; Black or African American; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Chi-Square Distribution; Creatinine; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Incidence; Kaplan-Meier Estimate; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States; Up-Regulation

The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease.. ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950.. The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group.. Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent.. Novartis.

Topics: Aged; Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Creatinine; Disease Progression; Diuretics; Double-Blind Method; Drug Combinations; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Risk Factors

In order to determine whether hypertension would develop in dogs with chronic renal failure, we performed 7/8 renal ablation in 6 healthy dogs and compared pre- and post-ablation blood pressures determined by telemetry. One month after the renal ablation, blood urea nitrogen and creatinine were significantly increased (p<0.05), creatinine clearance was decreased (p<0.05), and blood pressure was increased significantly (p<0.05). Simultaneously, plasma renin activity, angiotensin I and II, and aldosterone were elevated significantly (p<0.05) compared with the values obtained from 11 healthy dogs with intact renal function. The dogs with induced renal failure and hypertension were administered an angiotensin-converting enzyme inhibitor, benazepril hydrochloride, once daily for 2 weeks at 2 mg/kg body weight, and changes in blood pressure and the renin-angiotensin-aldosterone (RAA) system were determined. During the administration of benazepril hydrochloride, blood pressure, angiotensin II and aldosterone decreased significantly (p<0.05) and, upon discontinuation of administration, increased to the pre-administration levels (p<0.05). Plasma renin activity and angiotensin I showed no significant changes throughout the administration study. These results provide experimental evidence that hypertension develops in dogs with chronic renal failure through mechanisms involving the RAA system and demonstrate that benazepril hydrochloride improves renal hypertension in dogs.

Topics: Aldosterone; Angiotensin I; Angiotensin II; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Dog Diseases; Dogs; Female; Hypertension; Kidney Failure, Chronic; Male; Renin

We examined effects of an angiotensin converting-enzyme inhibitor, benazepril hydrochloride (BH), on renal hypertension and chronic renal failure (CRF) in cats. For experimental CRF, healthy cats (n=5) underwent 7/8 renal ablation. After renal insufficiency and hypertension were confirmed by blood urea nitrogen (BUN), serum creatinine, creatinine clearance and telemetric recording of systemic blood pressure, BH was administered orally once daily at 0.9 to 2.0 mg/kg/day for 2 to 3 weeks. Within 2 months after renal ablation, renal failure and hypertension developed as evidenced by significant increases in BUN, serum creatinine and systemic blood pressure (p<0.01 or 0.05) and significantly decreased creatinine clearance accompanied by elevated plasma renin activity, angiotensin I and II, and aldosterone (p<0.01 or 0.05). BH administration corrected systemic hypertension (p<0.05) and significantly reduced angiotensin II and aldosterone (p<0.05). Upon discontinuation of BH, these values returned to the pre-administration levels. Studies on spontaneous CRF enrolled 11 cats with spontaneously occurring CRF. BH was administered orally to 6 cats once daily for 24 weeks at a final dose of 1.0 mg/kg/day, while 5 cats served as control. BH administration reduced serum creatinine and urinary protein concentration in every cat. Results demonstrate that in cats, loss of renal mass leads to activation of the renin-angiotensin-aldosterone system and associated renal hypertension, and indicate that BH is effective in correcting renal hypertension and may provide renal benefits to cats with CRF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Cat Diseases; Cats; Dose-Response Relationship, Drug; Female; Kidney Failure, Chronic; Male

Angiotensin-converting-enzyme inhibitors provide renal protection in patients with mild-to-moderate renal insufficiency (serum creatinine level, 3.0 mg per deciliter or less). We assessed the efficacy and safety of benazepril in patients without diabetes who had advanced renal insufficiency.. We enrolled 422 patients in a randomized, double-blind study. After an eight-week run-in period, 104 patients with serum creatinine levels of 1.5 to 3.0 mg per deciliter (group 1) received 20 mg of benazepril per day, whereas 224 patients with serum creatinine levels of 3.1 to 5.0 mg per deciliter (group 2) were randomly assigned to receive 20 mg of benazepril per day (112 patients) or placebo (112 patients) and then followed for a mean of 3.4 years. All patients received conventional antihypertensive therapy. The primary outcome was the composite of a doubling of the serum creatinine level, end-stage renal disease, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease.. Of 102 patients in group 1, 22 (22 percent) reached the primary end point, as compared with 44 of 108 patients given benazepril in group 2 (41 percent) and 65 of 107 patients given placebo in group 2 (60 percent). As compared with placebo, benazepril was associated with a 43 percent reduction in the risk of the primary end point in group 2 (P=0.005). This benefit did not appear to be attributable to blood-pressure control. Benazepril therapy was associated with a 52 percent reduction in the level of proteinuria and a reduction of 23 percent in the rate of decline in renal function. The overall incidence of major adverse events in the benazepril and placebo subgroups of group 2 was similar.. Benazepril conferred substantial renal benefits in patients without diabetes who had advanced renal insufficiency. (ClinicalTrials.gov number, NCT00270426.)

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; China; Creatinine; Disease Progression; Double-Blind Method; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Renal Insufficiency, Chronic

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). The early stage of nephropathy is manifested by the presence of low levels of urinary albumin (microalbuminuria or urinary albumin excretion >or=30 and <299 mg/day). Albuminuria is a marker for development of nephropathy in type II diabetes and for increased cardiovascular morbidity and mortality. Recent studies have demonstrated the importance of antihypertensive agents that inhibit the renin-angiotensin-aldosterone (RAA) system to reduce the risk and slow down the progression of renal disease. A new clinical trial, GUARD (Gauging Albuminuria Reduction With Lotrel in Diabetic Patients With Hypertension), is designed to compare the change in urinary albumin to creatinine ratio after 1 year of initial treatment with either amlodipine besylate/benazepril HCl or benazepril HCl/hydrochlorothiazide. Other objectives include a comparison of the proportion of patients who progress to overt diabetic nephropathy and the safety of these two combination therapies in these high-risk patients.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diuretics; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Renin-Angiotensin System; Research Design; Sodium Chloride Symporter Inhibitors

Angiotensin-converting enzyme inhibitor (ACEI) has been demonstrated to have protective effect for patients with mild to moderate chronic kidney disease (CKD). However, little evidence is available for the benefit or side-effects of ACEI in treating patients with more severe CKD. A prospective, randomized controlled trial was performed to evaluate the renal protective effect and safety of ACEI in patients whose serum creatinine (Scr) levels were higher than 265 micromol/L.. 168 CKD patients took benazepril for two months. 21 patients quitted the trial because of cough. The remaining 147 CKD patients were divided into two groups according to their Scr levels. Patients with Scr 133 - 265 micromol/L were included in group A (n = 55), and those with Scr 266-442 micromol/L were included in group B (n = 92). Furthermore, group B were divided randomly into two subgroups, B1 (n = 47) and B2 (n = 45). Benazepril was given (10 - 20 mg/d) as an intervention for group A and group B1. Additional calcium-channel antagonist and/or beta-blocker and/or vasodilator were used for blood pressure control in those two groups. Patients in group B2 served as controls who take calcium-channel antagonist and/or beta-blocker and/or vasodilator but not Benazepril. The target blood pressure is 125/75 mm Hg or less in all groups. All patients were followed for two years. Doubling of the baseline Scr level or end-stage renal disease with the need for dialysis was regarded as the major end point of the trial.. (1) The magnitude of mean arterial pressure reduction was comparable in group A [(12.90 +/- 3.21) mm Hg], group B1 [(13.36 +/- 4.27) mm Hg] and group B2 [(10.38 +/- 3.85) mm Hg]. There was no significant change among them (P > 0.05 in all). (2) The magnitude of urinary protein reduction (Delta) in group A [(0.52 +/- 0.29) g/24 h], group B1 [(0.50 +/- 0.26) g/24 h] were much higher than that in group B2 [(0.19 +/- 0.13) g/24 h] (P < 0.05), but there was no significant difference between group A and B1 (P = 0.94). (3) By the end of two years, the percentages of cases reaching the major end point in group A, group B1 and group B2 were 19.23%, 40.90% and 51.35% respectively. There was significant difference among the three groups (chi(2) = 12.14, upsilon = 2, P = 0.002). (4) After two years of treatment, the left ventricular mass indexes and the percentages of left ventricular hypertrophy in group A, group B1 and group B2 were all decreased significantly. There were no statistical differences among the three groups. (5) The incidence of ACEI related adverse reactions, such as rapid increase of Scr more than 30%, dry cough or hyperkalemia were not different among the three groups.. Benazepril slows the progression of CKD in patients with Scr higher than 266 micromol/L, it is safe in these patients.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Creatinine; Disease Progression; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies

The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and alphabeta blocker in combination with a calcium antagonist on the progression of renal function and left ventricular hypertrophy (LVH) in patients with chronic renal insufficiency and hypertension. The 65 subjects in this study were recruited from a cohort of 316 patients. The main criteria for inclusion were echocardiographic diagnosis of LVH (posterior wall thickness >12 mm) and serum creatinine of more than 1.5 mg/dl. Antihypertensive treatments were switched to the combination of amlodipine at a dose of 5 mg and benazepril at a dose of 2.5 mg daily or the combination of amlodipine at a dose of 5 mg and arotinolol at a dose of 20 mg daily at random irrespective of whether or not patients had been previously treated. The follow-up period was 2 years. Systolic and diastolic blood pressure were significantly reduced from 150/90 +/- 15/11 mmHg to 130/75 +/- 11/9 mmHg (ACE) and the levels of serum creatinine were increased significantly from 1.8 +/- 0.3 to 2.0 +/- 0.4 mg/dl (ACE). In the alphabeta-blocker group, these two values were similar and no significant changes were found. PWT was decreased from 14.2 +/- 0.6 to 12.9 +/- 0.3 cm in alphabeta blocker but was not significantly decreased in the ACE inhibitor group. In conclusion, combination therapy with a calcium antagonist and abeta blocker might be effective treatment for hypertensive patients with chronic renal insufficiency and left ventricular hypertrophy.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Cohort Studies; Creatinine; Drug Therapy, Combination; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension, Renal; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Pilot Projects; Propanolamines; Proteinuria

Several experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker could provide a higher degree of blockade of the renin-angiotensin system than either agent alone. Such enhanced suppression might be of benefit for patients exhibiting a progressive decline in renal function because of chronic renal disease.. A pilot multinational, multicentre, randomized, active-controlled, parallel group open-label study has been conducted in a group of patients with progressive chronic renal failure (creatinine clearance 20-45 ml/min) either with or without proteinuria and hypertension. The primary aim of the study was to investigate the safety and tolerability of the combination of valsartan and benazepril. Patients were randomly assigned to one of three groups: group 1 received valsartan 160 mg once daily (n = 22); group 2 received valsartan 80 mg once daily plus benazepril 5 or 10 mg once daily (n = 42); group 3 received valsartan 160 mg once daily plus benazepril 5 or 10 mg once daily (n = 44). The study lasted for 5 weeks, and in groups 2 and 3 benazepril was added on top of valsartan after the first week of therapy with the angiotensin receptor blocker.. Serum creatinine increased in all three groups (mean change within a group: 11 micromol/l in group 1, P= 0.045; 9 micromol/l in group 2, P= 0.030; 15 micromol/l in group 3, P= 0.0006). Serum potassium also increased in all three groups of patients (mean change within a group: 0.28 mmol/l in group 1, P= 0.28; 0.48 mmol/l in group 2, P= 0.0008; 0.36 mmol/l in group 3, P= 0.02). After 5 weeks of treatment, the largest decrease in blood pressure was observed in group 3 (the mean change from baseline in seated diastolic blood pressure (SDBP) and seated systolic blood pressure (SSBP), respectively, were: -2.0 and -11.5 mmHg in group 1; -7.6 and -15.4 mmHg in group 2; -12.6 and -21.6 mmHg in group 3). In addition, both combination treatments resulted in the reduction of proteinuria. The total number of patients with adverse experiences were 10 (45.5%), 14 (33.3%) and 11 (25%) in groups 1,2 and 3, respectively. In six patients (5.6%) therapy was discontinued as a result of adverse experiences. Only one patient in each of the combined therapy groups withdrew from the study because of hyperkalaemia and no patients were forced to withdraw because of an increase in serum creatinine, acute renal failure or hospitalization.. These results indicate that short-term combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker is safe and well tolerated in patients with moderate chronic renal failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Creatinine; Drug Combinations; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Pilot Projects; Potassium; Proteinuria; Safety; Tetrazoles; Valine; Valsartan

A prospective, randomized, double-blind trial recently demonstrated that treating patients with chronic renal insufficiency with benazepril significantly decelerates the rate of progression of the disease. We tested the hypothesis that preventative treatment with the angiotensin converting enzyme (ACE) inhibitor benazepril in patients with chronic renal insufficiency is cost-effective. A Markov chain model was used that considered regular treatment, hemodialysis, continuous ambulant peritoneal dialysis, transplantation, rejection and death. Clinical trial data were used to estimate the effects of benazepril treatment and to estimate the duration until renal replacement therapy was needed. Epidemiologic parameters were derived on the basis of Dutch registries of renal diseases, costs are estimated by updating former estimates, literature review and expert opinion. We found that preventative treatment with benazepril decreased the percentage of patients who died or developed end-stage renal disease. Total costs per patient are expected to decrease in three years with more than $4,000 US per patient. Extrapolated to ten years, the savings are estimated at $23,500 US per patient. Benazepril treatment is not only an effective treatment in patients with chronic renal failure. By increasing the years spent without dialysis, it is also a cost-effective treatment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Costs and Cost Analysis; Creatinine; Double-Blind Method; Humans; Kidney Failure, Chronic; Markov Chains; Models, Economic; Prospective Studies; Renal Dialysis

Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases.. In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis.. At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group.. Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Disease Progression; Double-Blind Method; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Double-Blind Method; Humans; Kidney Failure, Chronic; Prospective Studies

Lotensin has been shown to have a protective function in the early stage of chronic renal failure. However, its role in the intermediate and late stages of chronic renal failure remains largely unknown. The present study aimed to investigate the role and underlying mechanism of lotensin in advanced chronic kidney disease.. Female Wistar rats were randomly divided into three groups (n = 10): sham group, 5/6 nephrectomy (5/6 Nx) group, and lotensin group (oral administration of lotensin for 9 weeks following 5/6 Nx). Rats were sacrificed and pathological parameters were measured. Western blot assay and immunohistochemical staining were performed to detect the expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in kidney tissues.. Compared to the 5/6 Nx group, lotensin administration significantly decreased 5/6 Nx-induced elevation in blood urea nitrogen, serum creatinine and 24-h urinary protein excretion (UPE) rates, but markedly increased red blood cell count, plasma albumin and hemoglobin levels, along with improved renal morphology. Mechanistically, lotensin dramatically downregulated the renal expression of TGF-β1 and α-SMA induced by 5/6 Nx.. Lotensin protects against advanced chronic kidney disease in rats with 5/6 Nx through the downregulation of TGF-β1 and α-SMA.

Topics: Actins; Animals; Benzazepines; Blood Urea Nitrogen; Creatinine; Female; Immunohistochemistry; Kidney; Kidney Failure, Chronic; Random Allocation; Rats; Rats, Wistar; Transforming Growth Factor beta1

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Calcium Channel Blockers; Creatinine; Disease Progression; Diuretics; Drug Therapy, Combination; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Kidney Failure, Chronic; Renin-Angiotensin System

There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS).. A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years.. The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens.. The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Benzazepines; Captopril; Child; Disease Progression; Drug Resistance; Enalapril; Female; Glomerulosclerosis, Focal Segmental; Humans; Incidence; Japan; Kidney Failure, Chronic; Male; Peptidyl-Dipeptidase A; Prednisolone; Proteinuria; Regression Analysis; Retrospective Studies; Survival Rate

The purpose of these studies was to compare the effects of CGS 30440 (CGS), a dual angiotensin-converting enzyme inhibitor (ACEI)/neutral endopeptidase inhibitor (NEPI) to benazepril (BZ), an ACEI, in a model of five-sixths nephrectomy. The doses of BZ and CGS 30440 tested were 6.5 micromol/kg/day and 2.2 micromol/kg/day. Drugs or vehicle (V) were administered subcutaneously for 6 weeks with dosing initiated 1 week after renal mass reduction. At 6 weeks of receiving drug (7 weeks after five-sixths nephrectomy), CGS/6.5 and BZ/6.5 and CGS/2.2 maintained systolic blood pressures (SBP) at presurgical values. BZ/2.2 did not reduce SBP and was similar to the V group. Urinary protein excretion increased >10-fold in the V-treated group. BZ, at either dose, reduced the proteinuria slightly. CGS/6.5 and CGS/2.2 caused significant (p < 0.05) reductions in proteinuria. Creatinine clearance (Cr(cl)), was reduced by 82% in V, 65 and 61% in the CGS/6.5 and CGS/2.2 groups, and by 69 and 74% in the BZ/6.5 and BZ/2.2 groups, respectively. Both CGS treatments improved the fractional excretion of Na+ (%FE(Na)) significantly from the BZ and V groups. The %FE(Na) for BZ at either dose did not differ from that of V. Elevated urinary cyclic guanosine monophosphate (cGMP), an indicator suggesting increased intrarenal levels of atrial natriuretic peptide (ANP), was observed only in the CGS groups. Histologic examination indicated that BZ/6.5 reduced glomerular sclerosis and the extent of tubular dilation, whereas BZ/2.2 had little effect. CGS, especially at the high dose, virtually normalized the glomerular and tubular pathology. Compared with BZ, CGS 30440 treatment further diminished tubular dilation and proteinaceous cast formation. These tubular effects are consistent with some of the renal actions of ANP. The results from these studies indicate that CGS 30440, a combined ACEI/NEPI, conferred a greater renal protective effect than did ACE inhibition alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Creatinine; Cyclic GMP; Electrolytes; Kidney; Kidney Failure, Chronic; Male; Nephrectomy; Neprilysin; Protease Inhibitors; Proteinuria; Rats; Rats, Sprague-Dawley; Tyrosine

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Humans; Kidney Failure, Chronic

Benazepril (Lotensin) is an ACE inhibitor that can be safely used in renal and liver disease. Statistical analysis of both single and repeated 10 mg oral doses shows no significant difference in action between young patients and those over 55. All ACE inhibitor drugs are in a homogenous class. One advantage that benazepril has over the others is convenience. It can be taken any time of day, with or without food, and most often is only needed once a day. This is important to our patients who are on multiple medication regimens. There are no clinically important pharmacologic interactions with digoxin, warfarin, naproxen, cimetidine, hydrochorothiazide, furosemide, propranolol, atenolol, or chlorthalidone.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Drug Costs; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis

The pharmacokinetics and pharmacodynamics of benazepril, an angiotensin converting enzyme (ACE) inhibitor, were investigated after administration of a single oral 5-mg dose and 7 more doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with impaired renal function (IRF). The antihypertensive effect of benazepril was observed as early as 30 min after a single dose, and those effects during consecutive dosing were also sustained for 24 h with a lesser diurnal variation in blood pressure (BP). The time to peak (Tmax) and the apparent elimination half-life (t1/2) for benazepril were 0.6-0.7 h and 0.4-0.8 h, respectively. Tmax for its diacid was 1.5-2.4 h in both groups. The area under the plasma concentration-time curve to 24 h (AUC0-24h) for the diacid was significantly greater in the IRF group than in the NRF group. After consecutive dosing of benazepril, AUC0-24h and plasma peak level (Cmax) were significantly increased in the IRF group. Serum ACE activity was markedly suppressed for 24 h after administration, and the inhibition was closely related to plasma diacid levels. A significant inverse correlation was observed between creatinine clearance and the AUC for the diacid. These results suggest that benazepril is rapidly bioactivated to diacid and exhibits rapid onset and long-lasting antihypertensive effects. Dosage reduction might be required to minimize unnecessary drug accumulation in patients with severe IRF.

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Hypertension, Renal; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Peptidyl-Dipeptidase A; Radioimmunoassay

To investigate the pharmacokinetics of benazepril hydrochloride in special populations, single or multiple doses between 5 and 20 mg of the new drug were given, and the pharmacokinetics of unchanged benazepril and its pharmacologically active metabolite benazeprilat were compared with those in healthy male volunteers. In elderly subjects and patients with mild and moderate renal insufficiency, there was little change in the kinetics of benazepril or benazeprilat. In patients with severe renal impairment (creatinine clearance less than 30 ml/min), benazeprilat elimination was slowed, which resulted in greater accumulation after repeated dosing. In patients with hepatic cirrhosis, the kinetics and bioavailability of benazeprilat were not affected. Therefore dose adjustment is unnecessary because of the patient's age, mild or moderate renal impairment, or hepatic cirrhosis. Dose reduction is necessary in patients with creatinine clearance less than 30 ml/min.

Topics: Aged; Aged, 80 and over; Benzazepines; Dose-Response Relationship, Drug; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Liver Cirrhosis; Male; Metabolic Clearance Rate