benazepril and Renal-Insufficiency

This study investigated whether proteinuria not only could serve as a marker of renal outcome but also could monitor the renoprotection of renin-angiotensin system (RAS) inhibitor treatment in patients with nondiabetic chronic kidney disease (CKD). Data from the Renoprotection of Optimal Antiproteinuric Doses (ROAD) trial were used to examine the contribution of the antiproteinuric effect of benazepril and losartan on renal outcome (the primary composite end point of doubling of serum creatinine and end-stage renal disease or death) in 339 Chinese nondiabetic CKD patients with overt proteinuria and renal insufficiency. The degree of proteinuria at month 6 of treatment (residual proteinuria) and during follow-up (time-average proteinuria) showed a close relationship with renal end points. Lowering of proteinuria reduced the risk of renal progression in patients with high, as well as low, proteinuria at baseline. After adjustment for baseline risk markers, therapy-induced change in these variables at month 6 and during follow-up--high residual proteinuria and time-average proteinuria (≥ 1.0 g/d)--remained the independent predictors for renal end points. Therefore, minimization of proteinuria at least to less than 1.0 g/d should be a therapeutic goal in the management of nondiabetic patients with heavy proteinuria and renal insufficiency.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Biomarkers; China; Disease Progression; Drug Monitoring; Female; Follow-Up Studies; Humans; Kidney; Losartan; Male; Middle Aged; Proportional Hazards Models; Proteinuria; Renal Insufficiency; Renin-Angiotensin System; Severity of Illness Index; Treatment Outcome

The role of angiotensin-converting enzyme inhibitors (ACEI) in contrast-induced acute kidney injury (CI-AKI) is controversial. Some studies pointed out that it was effective in the prevention of CI-AKI, while some concluded that it was one risk for CI-AKI, especially for patients with pre-existing renal impairment. The purpose of this study was to assess the influence of benazepril administration on the development of CI-AKI in patients with mild to moderate renal insufficiency undergoing coronary intervention.. One hundred and fourteen patients with mild to moderate impairment of renal function were enrolled before coronary angioplasty, who were randomly assigned to benazepril group (n = 52) and control group (n = 62). In the benazepril group, the patients received benazepril tablets 10 mg per day at least for 3 days before procedure. CI-AKI was defined as an increase of ≥ 25% in creatinine over the baseline value or increase of 0.5 mg/L within 72 hours of angioplasty.. Patients were well matched with no significant differences at baseline in all measured parameters between two groups. The incidence of CI-AKI was lower by 64% in the benazepril group compared with control group but without statistical significance (3.45% vs. 9.68%, P = 0.506). Compared with benazepril group, estimated glomerular filtration rate (eGFR) level significantly decreased from (70.64 ± 16.38) ml · min⁻¹·1.73 m⁻² to (67.30 ± 11.99) ml · min⁻¹·1.73 m⁻² in control group (P = 0.038). There was no significant difference for the post-procedure decreased eGFR from baseline (ΔeGFR) between two groups (benazepril group (0.67 ± 12.67) ml · min⁻¹·1.73 m⁻² vs. control group (-3.33 ± 12.39) ml · min⁻¹·1.73 m⁻², P = 0.092). In diabetic subgroup analysis, ΔeGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant.. Benazepril has a protective effect on mild to moderate impairment of renal function during coronary angioplasty. It is safe to use benazepril for treatment of patients with mild to moderate impairment of renal function before coronary intervention.

Topics: Acute Kidney Injury; Aged; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Contrast Media; Coronary Angiography; Female; Humans; Male; Middle Aged; Renal Insufficiency

The present study examined the effects of benazepril, an angiotensin-converting enzyme inhibitor, on the progression of renal insufficiency in patients with non-diabetic renal disease.. Fifteen patients with non-diabetic renal disease whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dL were given either benazepril (2.5-5 mg) or placebo once daily for 1 year in a random crossover manner. In both periods, antihypertensive medications were increased if blood pressure was greater than 130/85 mmHg. Blood sampling and urinalysis were performed bimonthly throughout the study period.. Blood pressure was similar when comparing the benazepril and the placebo periods (128+/-12/83+/-6 vs 129+/-10/83+/-7 mmHg). Serum Cr significantly increased from 1.62+/-0.18 to 1.72+/-0.30 mg/dL (P=0.036) during the placebo period, while there was no statistically significant increase in serum Cr during the benazepril period (from 1.67+/-0.17 to 1.71+/-0.27 mg/dL). The slope of decrease of the reciprocal of serum Cr was steeper in the placebo period than in the benazepril period (-0.073+/-0.067 vs-0.025+/-0.096/year, P=0.014). Urinary protein excretion was lower during the benazepril period than during the placebo period (0.57+/-0.60 vs 1.00+/-0.85 g/gCr, P=0.006). Serum K was significantly higher in the benazepril period than in the placebo period (4.4+/-0.5 vs 4.2+/-0.5 mEq/L, P<0.001), but no patient discontinued benazepril therapy as a result of hyperkalemia.. Long-term benazepril treatment decreased the progression of renal dysfunction in patients with non-diabetic renal disease by a mechanism that is independent of blood pressure reduction.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Creatine; Cross-Over Studies; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Proteinuria; Renal Insufficiency

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

The effect of renal insufficiency was studied on the pharmacokinetics (PK) and pharmacodynamics (PD) of the angiotensin-converting enzyme (ACE) inhibitor benazepril in cats. The active metabolite of benazepril, benazeprilat, is eliminated principally ( approximately 85%) via biliary excretion in cats. A total of 20 control animals and 32 cats with moderate renal insufficiency induced by partial nephrectomy were used. Assessments were made at steady state after treatment with placebo or benazepril (0.25-2 mg/kg) once daily for a minimum of 10 days. The PK endpoint was the AUC (0-->24 h) of total plasma benazeprilat. The PD endpoints were systolic, diastolic and mean blood pressures (respectively SBP, DBP and MBP) measured by telemetry, and plasma ACE activity, assessed by an ex vivo assay. Renal function was assessed by glomerular filtration rate (GFR), measured by inulin clearance, and plasma creatinine concentrations (1/PCr). As compared with control animals, the renal insufficient cats had a 78% reduction in GFR (0.57 +/- 0.41 mL/min kg), increased plasma creatinine (2.7 +/- 1.0 mg/dL), urea (44.0 +/- 11.9 mg/dL) and ACE activity, and moderately increased blood pressure (SBP 171.8 +/- 5.1 mmHg) (all parameters P < 0.05). Renal insufficient cats receiving benazepril had significantly (P < 0.05) lower SBP, DBP, MBP and ACE, and higher GFR values as compared with placebo-treated animals. There were no significant differences in SBP, DBP, MBP, benazeprilat or ACE values according to the degree of renal insufficiency in cats receiving benazepril. It is concluded that no dose adjustment of benazepril is necessary in cats with moderate renal insufficiency.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Area Under Curve; Benzazepines; Blood Pressure; Cat Diseases; Cats; Creatinine; Female; Kidney; Kidney Function Tests; Male; Renal Insufficiency

A protective effect of angiotensin-converting enzyme (ACE) inhibitors has been shown in patients with diabetic nephropathy but has not been clearly established in nondiabetic renal disease. A multicenter European study was designed to determine whether the ACE inhibitor benazepril was safe and effective in protecting residual renal function in patients with various renal diseases and mild to moderate renal failure. The trial involved 583 patients from 49 centers in Italy, France, and Germany. The patients were randomized to receive benazepril or placebo plus other antihypertensive agents, the target being a diastolic blood pressure of less than 90 mm Hg. Thirty-one patients in the benazepril group and 57 patients in the placebo group reached the end point [the time elapsed from entry to (a) doubling of serum creatinine (SCr) concentrations and (b) start of renal replacement therapy; p < 0.001 at 3 years]. The associated reduction in the relative risk of reaching the end point was 53% in benazepril-treated patients, with actuarial renal survival probability significantly better at 3 years. The best survival of renal function was observed in patients with chronic glomerular diseases and proteinuria greater than 1.0 g/24 h. Benazepril is effective in slowing the rate of progression and improving the survival of renal function in patients with renal diseases of various origins. This protective effect is associated with a clinically relevant decrease in both blood pressure and proteinuria.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Creatinine; Female; Humans; Kidney Diseases; Male; Placebos; Prospective Studies; Proteinuria; Renal Insufficiency

Personalized dosing regimens have great potential to improve the standard level of care from "one-fits-all" to the "right dose, to the right patient at the right time".. Development of a digital interface that can inform healthcare professionals on the dosing of an ACE inhibitor on an individual basis.. A physiologically based pharmacokinetic (PBPK) model and a one-compartment model were implemented for the prodrug benazepril and its metabolite benazeprilat, respectively. In sequence, to capture inter-individual differences the models were extended to a population based one (PopPBPK).. Both models predicted the pharmacokinetic data in the observed ranges. Application of the models help identify the factors influencing drug concentrations in the body and to find subgroups of patients, in which a dose adjustment is recommended, or a higher degree of caution is required.. The use of the models via a practical user interface can help inform clinical decisions and design optimal dosing based on the individual anthropometric characteristics and stage of renal impairment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Humans; Kidney; Models, Biological; Renal Insufficiency

To explore the effect of benazepril (one of angiotesin converting enzymes) on the expression of vascular endothelial growth factor (VEGF) and the change of microvessel density (MVD) in the remnant kidney of rats that undergone 5/6 subtotal nephrectomy (STNx).. The male Sprague-Dawley (SD) rats were performed 5/6 nephrectomy to produce chronic renal failure, and randomly divided into a model group (STNx group), a STNx combined with benazepril group (Benazepril group), and a sham group that served as normal controls. Pathological changes of the remnant kidney were evaluated at the 8th week after gastric gavage. Immunohistochemistry Methods were used to examine the expression of VEGF and MVD in the remnant kidney, and the correlation was determined between VEGF, MVD and glomerulosclerosis index (GSI), tubulointerstitial score (TIS), BUN, and creatinine (Cr).. UP, BUN, Cr, GSI, and TIS significantly decreased in the benazepirl group (P<0.05); and the expression of VEGF and MVD significant increased (P<0.05). The expression of VEGF was positively related to MVD (P<0.05), and there was negative correlation between VEGF, MVD and GSI, TIS, BUN, Cr (P<0.05).. The decrease of the expression of VEGF and MVD in the remnant kidney may be involved in the progressive remnant kidney fibrosis and renal function. Benazepril can significantly relieve the remnant kidney fibrosis and protect the renal function by increasing the expression of VEGF and MVD in the remnant kidney.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Capillaries; Kidney; Male; Nephrectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Vascular Endothelial Growth Factor A

The transport capacity of any membrane depends on its surface area and permeability. In addition, peritoneal capillaries are probably barriers to solute transport. Although no decisive use of antihypertensive drugs has been reported in continuous ambulatory peritoneal dialysis (CAPD) patients with hypertension, those drugs are known to have various effects on vessels. In the present study, we used a charge-coupled-device (CCD) camera in renovascular hypertensive dogs with mild renal insufficiency to investigate the effects of various antihypertensive drugs on the peritoneal capillaries. Renovascular hypertension was induced in the dogs by placing silver clips on both renal arteries to create 90% occlusion. After confirmation of elevation of blood pressure (usually 20 days after the operation), each dog's abdomen was opened while the animal was under general anesthesia. Using a CCD camera, the diameters of the small arteries of the peritoneum were measured after 3 days' oral administration of a placebo (n = 5); or of 8 mg CS866, a selective angiotensin II type 1 receptor blocker (n = 5); or of 10 mg benazepril, an angiotensin-converting enzyme inhibitor (n = 5); or of 10 mg amlodipine, a calcium antagonist (n = 5). In dogs receiving CS866, blood pressure decreased to 128 +/- 6 mmHg from 160 +/- 6 mmHg (p < 0.01). A similar decrease in blood pressure was observed with the use of the other drugs. The diameter of the small vessels increased by 28% +/- 6% in dogs receiving CS866 and by 24% +/- 5% in dogs receiving benazepril, as compared with 3% +/- 3% in dogs receiving the calcium antagonist. These data clearly demonstrate that blockade of the renin-angiotensin system produces an increase in solute clearance in hypertensive dogs with mild renal insufficiency and that such blockade may be applicable as therapy for hypertensive patients on CAPD.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Aquaporins; Benzazepines; Blood Pressure; Calcium Channel Blockers; Dogs; Hypertension, Renovascular; Imidazoles; Microcirculation; Olmesartan Medoxomil; Peritoneum; Renal Insufficiency; Tetrazoles; Vasodilation

The influence of a renal injury on the disposition of benazeprilat, the active moiety of benazepril, and of enalaprilat, the active moiety of enalapril, two angiotensin-converting enzyme (ACE) inhibitors (ACEI), having different routes of elimination in dog was investigated during a mild renal insufficiency obtained by a nephrectomy-electrocoagulation method reducing glomerular filtration rate by approximately 50%. Plasma concentrations of the active moieties were analyzed with a physiologically based model taking into account the binding to ACE (high affinity, low capacity). An influence of renal insufficiency on enalapril disposition was shown with an increase in its plasma concentration, which was correlated to the reduction of the glomerular filtration rate. No such effect was evidenced for benazepril. With the physiologically based model analysis, it was shown that renal impairment led to an increase of the apparent benazeprilat clearance (260%), whereas that of enalaprilat was reduced to 40 to 55%. Renal insufficiency had no significant effect either on the apparent volume of distribution of each drug or on the binding parameters [i.e., maximal binding capacity (B(max)) and affinity (K(d))]. Enalaprilat and benazeprilat inhibitory action on ACE also was evaluated ex vivo. Similar patterns of inhibition were observed for both drugs. Renal injury had no significant influence on the overall effect of benazeprilat, whereas the inhibition effect of enalaprilat was significantly increased. It was concluded that renal insufficiency may have effects on the ACEI disposition but that the measurable active moiety plasma concentration is not the most appropriate endpoint to describe and interpret the consequence of a renal injury on ACEI.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Dogs; Enalapril; Female; Models, Biological; Prodrugs; Regression Analysis; Renal Insufficiency