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Research
Abstracts and Papers. |
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J Vet Med Sci. 2007 Oct;69(10):1015-23 Effects of benazepril hydrochloride in cats with experimentally induced or spontaneously occurring chronic renal failure. Watanabe T, Mishina M. Department of Surgery, School of Veterinary Medicine, Azabu University, and Department of Nephrology and Urology, Teaching Animal Hospital, Kanagawa, Japan. 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. |
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J Vet Intern Med. 2007 Sep-Oct;21(5):906-16. Prognostic factors in cats with chronic kidney disease. King JN, Tasker S, Gunn-Moore DA, Strehlau G; BENRIC (benazepril in renal insufficiency in cats) Study Group. From Novartis Animal Health Inc, Postfach, CH?4058, Basel, Switzerland (King, Strehlau); the Department of Veterinary Clinical Science, School of Clinical Veterinary Science, University of Bristol, Langford, Bristol, UK (Tasker); and the Department of Veterinary Clinical Studies, University of Edinburgh Veterinary Hospital for Small Animals, Easter Bush, Midlothian, UK (Gunn?Moore). Novartis Animal Health Inc, Postfach, CH-4058, Basel, Switzerland. jonathan.king@novartis.com BACKGROUND: Chronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. HYPOTHESIS: Some baseline variables are associated with shorter survival times in cats with CKD. ANIMALS: Client-owned cats. METHODS: Cats with CKD with initial plasma creatinine concentration > or =2.0 mg/dL and urine specific gravity (USG) < or = 1.025 were recruited into a prospective clinical trial that compared benazepril with a placebo. We describe baseline variables in 190 cats and their influence on renal survival time in the placebo group (95 cats), which was followed for up to 1,097 days. Renal survival time was defined as the time from initiation of therapy to the need for parenteral fluid therapy, euthanasia, or death related to renal failure. RESULTS: Of the 95 cats treated with a placebo, 58 were censored and 37 reached the renal survival end point (died, n = 0; euthanized, n = 17; parenteral fluids, n = 12; parenteral fluids followed by euthanasia, n = 8). Increased plasma creatinine concentration, increased urine protein-to-creatinine ratio (UPC), and increased blood leukocyte count were significantly (P < .01) associated with a shorter renal survival time and were independent risk factors. Increased concentrations of plasma phosphate or urea, and lower blood hemoglobin concentration or hematocrit were significantly (P < .01) associated with a shorter renal survival time and were dependent risk factors, because they also were significantly (P < .01) correlated with plasma creatinine concentration at baseline. CLINICAL IMPORTANCE: Several variables were significantly associated with a shorter renal survival time in cats with CKD. The BENRIC Study Group consisted of the following investigators, location (number of cats included in the trial): Ash RA, Brighton, UK (39); Bussadori C and Bonfanti U, Milan, Italy (23); Papadopulo I, Villefontaine, France (20); Santilli S and Ghibaudo G, Samarate and Varese, Italy (15); Lanore D, Plaisance du Touch, France (11); Clarke DD, King's Lynn, UK (9); Gleadhill A, Harrogate, UK (9); Gunn-Moore DA, Mackin A and Tasker S, Edinburgh, UK (9); Varga K, Wanstead, UK (9); Cotard JP and Jacquemin N, Maisons Alfort, France (7); Crowe ID, Skipton, UK (7); Rousselot JF, Trappes, France (7); Stonton SA, Peterborough, UK (7); De Geyer G, Angers, France (5); Dossin O, Toulouse, France (4); Hagege G, Nogent sur Marne, France (4); Arthur J, Bognor Regis, UK (3); Brovida C, Moncalieri and Turin, Italy (3); Pechereau D and Martel P, Pau, France (3); Closa JM and Font A, Barcelona, Spain (2); Laforge H, Paris, France (2); Piette MH, Fontainebleau, France (2); Do Chi T, Biganos, France (1). |
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Journal of Veterinary Internal Medicine, Article: pp. 402–409 | Abstract, Volume 21, Issue 3 (May 2007) Effect of Control of Systolic Blood Pressure on Survival in Cats with Systemic Hypertension Rosanne E. Jepson, Jonathan Elliott, David Brodbelt, and Harriet M. Syme Background: Systemic hypertension is a common clinical problem, often occurring in association with renal disease in cats. Limited information is available to assess the effect of blood pressure and the treatment of hypertension on survival. Hypothesis: That adequacy of blood pressure control is associated with the duration of survival in cats with systolic hypertension. Animals: One hundred and forty-one client-owned cats with systolic hypertension. Methods: Hypertensive cats were treated with amlodipine besylate and were followed until death or the study end point. Time-averaged systolic blood pressure (SBPOT) after implementation of antihypertensive medication and stabilization of systolic blood pressure (SBP) was calculated by using the equation (area under the curve/survival [days]). Cats were divided into quartiles based on their SBPOT, representing varying levels of blood pressure control (median [25th, 75th percentile]: Q1 = 137 [132, 141] mm Hg, Q2 = 148 [145, 151] mm Hg, Q3 = 157 [155, 158] mm Hg, Q4 = 170 [164, 175] mm Hg). Survival and clinical variables were compared between the quartiles. Cox proportional hazard regression analysis was used to determine the association of age, renal function, proteinuria, SBPOT, and the presence of hyperthyroidism on survival. Urine protein to creatinine ratio (UP : C) was compared at diagnosis of hypertension and after initiating treatment. Results: Only UP : C and SBP at diagnosis differed significantly between SBPOT quartiles. Proteinuria was the only variable significantly related to survival in hypertensive cats. A significant decline in UP : C was found in cats treated with amlodipine besylate. Conclusions and Clinical Importance: Proteinuria before and after treatment of hypertension is strongly associated with survival in cats with systolic hypertension. Treatment with amlodipine besylate can result in a significant reduction in UP : C. |
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Vet Clin North Am Small Anim Pract. 2007 Mar;37(2):283-95, vi-vii. Measurement, interpretation, and implications of proteinuria and albuminuria. Grauer GF, Department of Clinical Sciences, College of Veterinary Medicine, 111B Mosier Hall, Kansas State University, Manhattan, KS 66506, USA. ggrauer@vet.k-state.edu Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats. PMID: 17336676 [PubMed - indexed for MEDLINE] |
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Curr Pharm Des. 2007;13(13):1347-61. Angiotensin-converting enzyme inhibitors in veterinary medicine. Lefebvre HP, Brown SA, Chetboul V, King JN, Pouchelon JL, Toutain PL. UMR 181 INRA-ENVT Physiopathologie et Toxicologie Expérimentales, National Veterinary School, Toulouse cedex 03, France. h.lefebvre@envt.fr Angiotensin-converting enzyme (ACE) inhibitors represent one of the most commonly used categories of drugs in canine and feline medicine. ACE inhibitors currently approved for use in veterinary medicine are benazepril, enalapril, imidapril and ramipril. They are all pro-drugs administered by oral route. A physiologically based model taking into account the saturable binding to ACE has been developed for pharmacokinetic analysis. The bioavailability of the active compounds from their respective pro-drug is low. The active metabolites are eliminated by renal, hepatorenal or biliary excretion, according to the drug. The elimination half-life of the free fraction of the active compounds is very short (ranging from approximately 10 min to 2 h). ACE inhibitors are generally well tolerated. Benazepril, enalapril, imidapril and ramipril are approved for dogs with chronic heart failure (CHF). The efficacy of ACE inhibitors has been convincingly demonstrated in dogs with CHF, especially in those with chronic valvular disease. In such clinical settings, ACE inhibitors improve hemodynamics and clinical signs, and increase survival time. In cats with cardiovascular disease, little information is available except for reports of some benefit in cats with hypertrophic cardiomyopathy in two non-controlled investigations. ACE inhibitors have also a mild to moderate hypotensive effect. There is also evidence to recommend ACE inhibitors in dogs and cats with chronic renal failure (CRF). They decrease the glomerular capillary pressure, have antiproteinuric effects, tend to delay the progression of CRF and to limit the extent of renal lesions. |
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Journal of Veterinary Internal Medicine, pp. 1054–1064, Volume 20, Issue 5 (September 2006) Tolerability and efficacy of benazepril in cats with chronic kidney disease. Jonathan N. King, Danielle A. Gunn-Moore, Séverine Tasker, Allison Gleadhill, and Günther Strehlau, and The BENRIC (BENazepril in Renal Insufficiency in Cats) Study Group From the Novartis Animal Health Inc, Postfach, CH-4002, Basel, Switzerland (King, Strehlau); the Department of Veterinary Clinical Studies, University of Edinburgh Veterinary Hospital for Small Animals, Easter Bush, Midlothian, UK (Gunn-Moore); the Department of Clinical Veterinary Science, University of Bristol, Langford, Bristol, UK (Tasker); and Harrogate, North Yorkshire, UK (Gleadhill). Novartis Animal Health Inc, Postfach, Basel, Switzerland. jonathan.king@novartis.com The objective of the study was to test the effect of the angiotensin-converting enzyme inhibitor (ACEI) benazepril in cats with chronic kidney disease (CKD). A total of 192 cats with CKD with an initial plasma creatinine concentration ?2 mg/dL (?177 µmol/L) and urine specific gravity ?1.025 were recruited into a double-blind, parallel-group, prospective, randomized clinical trial. Cats received daily (q24h) PO placebo (n = 96) or benazepril·HCl at a dosage of 0.5–1.0 mg/kg (n = 96) for up to 1,119 days. Most cats were fed exclusively a diet containing low amounts of phosphate, protein, and sodium. Benazepril produced a significant reduction in proteinuria, assessed by the urine protein-to-creatinine ratio (UPC, P = .005). This effect of benazepril was present in all subgroups tested, including cats with UPC <0.2, although the effect was largest in cats with higher UPCs. Plasma protein was maintained at higher concentrations with benazepril as compared with placebo during treatment in cats with initial UPC <1 (P = .038 versus P = .079 for all cats). There was no difference in renal survival time between the 2 groups when all 192 cats were compared. Mean ± SD renal survival times were 637 ± 480 days with benazepril and 520 ± 323 days with placebo (P = .47). Mean ± SD renal survival times in the 13 cats with initial UPC ?1 were 402 ± 202 days with benazepril and 149 ± 90 days with placebo (P = .27). Cats with initial UPC ?1 treated with benazepril had better appetite (P = .017) as compared with those treated with placebo. Benazepril was well tolerated. In conclusion, benazepril decreased proteinuria in cats with CKD. |
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1: J Vet Intern Med. 2006 Sep-Oct;20(5):1074-9. Evaluation of the clinical efficacy of benazepril in the treatment of chronic renal insufficiency in cats. Mizutani H, Koyama H, Watanabe T, Kitagawa H, Nakano M, Kajiwara K, King
JN. Division of Veterinary Internal Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan. hisashi-m@nvau.ac.jp BACKGROUND: Chronic renal insufficiency (CRI) is a common disease in cats. Angiotensin-converting enzyme inhibitors (ACEI) have beneficial effects in humans with CRI by reducing the loss of protein in the urine and increasing life expectancy. HYPOTHESIS: The ACEI benazepril has beneficial effects on survival, clinical variables, or both as compared with placebo in cats with CRI. ANIMALS: 61 cats with naturally occurring CRI. METHODS: The cats were enrolled into a prospective, randomized, double-blind, placebo-controlled clinical trial. Cats received placebo or 0.5-1 mg/kg benazepril once daily for up to 6 months. RESULTS: Urine protein/urine creatinine ratios were significantly (P < .05) lower with benazepril as compared with placebo at days 120 and 180. Three cats with placebo and 1 cat with benazepril were removed prematurely from the study because of deterioration of CRI or death. Cats were classified into 4 stages of CRI according to the International Renal Interest Society (IRIS) classification scheme. Incidence rates of cats with IRIS classification stage 2 or stage 3 that remained in stage 2 or 3 without progressing to stage 4 were higher with benazepril (93 +/- 5%) as compared with placebo (73 +/- 13%). CLINICAL IMPORTANCE: These results suggest a potential for benazepril to delay the progression of disease, extend survival time, or both in cats with CRI. |
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J Vet Pharmacol Ther. 2006 Jun;29(3):225-7. Benazepril increases feed intake and body weight in healthy growing cats. King JN, Seewald W, King S, Goldenthal E. Novartis Animal Health Inc., Basel, Switzerland. jonathan.king@novartis.com |
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Journal of Veterinary Internal Medicine, Article: pp. 528–535
| Abstract, Volume 20, Issue 3 (May 2006) Harriet M. Syme, Peter J. Markwell, Dirk Pfeiffer, and Jonathan Elliott Tubulointerstitial kidney disease is a common cause of illness and death in pet cats and is typically not associated with overt proteinuria. Proteinuria would be independently related to survival in cats with renal failure, with or without hypertension. The study included 136 client-owned cats; 28 apparently normal, 14 hypertensive but not azotemic, 66 azotemic but not hypertensive, and 28 both hypertensive and azotemic. Cox's proportional hazards model was used to determine the influence of initial plasma creatinine concentration, proteinuria (urine protein-to-creatinine ratio or albumin-to-creatinine ratio), age, and systemic hypertension on the risk of death or euthanasia during the follow-up period. Multivariable linear regression was used to determine the relation between severity of proteinuria and predictive variables, including age, plasma creatinine concentration, systolic blood pressure, sex, and urine specific gravity. Plasma creatinine concentration and proteinuria were very highly related to survival. The hazard ratio (95% confidence intervals) for death or euthanasia was 2.9 (1.4–6.3) and 4.0 (2.0–8.0) for urine protein-to-creatinine ratio 0.2–0.4 and >0.4, respectively, compared with the baseline group with a urine protein-to-creatinine ratio of <0.2 and were 2.4 (1.2–4.8) and 4.9 (2.3–10.2) for an albumin-to-creatinine ratio of 30–82 mg/g and <82 mg/g, respectively, compared with a baseline group with albumin-to-creatinine ratio of <30 mg/g. Treated hypertensive cats did not have reduced survival, although systolic blood pressure, together with plasma creatinine concentration was positively related to the magnitude of proteinuria. Despite the relatively low concentrations of proteinuria typical of chronic renal disease in cats, this measurement is of prognostic significance. |
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Can Vet J. 2006 May; 47(5): 437–445. Benazepril and subclinical feline hypertrophic cardiomyopathy: A prospective, blinded, controlled study Mylène Taillefercorresponding author and Rocky Di Fruscia, Companion Animal Research Group, Small Animal Veterinary Teaching Hospital, Université de Montréal, 3200, Sicotte Street, PO Box 5000, Saint-Hyacinthe, Quebec J2S 7C6. Twenty-one cats with hypertrophic cardiomyopathy were enrolled in this study to determine if the administration of benazepril (0.5 mg/kg body weight [BW], PO, q24h) to cats with subclinical hypertrophic cardiomyopathy improves cardiac diastolic function and reverses left ventricular hypertrophy when compared with diltiazem controlled delivery (CD) (10 mg/kg BW, PO, q24h). Cats were evaluated at day 0 and after 3 and 6 months of therapy. In the benazepril group (n = 11), the diastolic transmitral flow of the E and A waves ratio (E/A ratio) increased significantly between 0 and 6 months (P = 0.009) and the thickness of the left ventricular free wall in systole (LVFWs) decreased significantly between 0 and 3 months (P = 0.04). In the diltiazem CD group (n = 5), none of the parameters varied significantly throughout the study. There was no difference between the benazepril and the diltiazem CD group throughout the study. Therefore, the variations observed for the E/A ratio and the LVFWs may have been incidental. Further studies will be needed to establish the role of benazepril in subclinical hypertrophic cardiomyopathy in cat. |
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[Human Study -- included because of its importance.] N Engl J Med. 2006 Jan 12;354(2):131-40. Efficacy and Safety of Benazepril for Advanced Chronic Renal Insufficiency Background 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. Methods 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. Results 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. Conclusions Benazepril conferred substantial renal benefits in patients without diabetes who had advanced renal insufficiency. |
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Journal of Veterinary Internal Medicine, Volume 19, Issue 3 (May-June 2005), Article: pp. 377–385 Assessment and Management of Proteinuria in Dogs and Cats: 2004 ACVIM Forum Consensus Statement (Small Animal) George E. Lees, Scott A. Brown, Jonathan Elliott, Gregory F. Grauer, and Shelly L. Vaden NOTE: Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of the Consensus Statement is evidence-based medicine, but if such evidence is conflicting or lacking the panel provides interpretive recommendations based on their collective expertise. The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents with input from the general membership. A draft is prepared and input from Diplomates is solicited at the Forum and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by the Board of Regents of the ACVIM before publication. Emerging data indicate that more attention should be given to the detection, evaluation, monitoring, and treatment of dogs and cats with proteinuria. The purposes of this consensus statement are to describe an appropriate approach for accomplishing these tasks and to provide specific recommendations for assessing and managing dogs and cats with proteinuria based on data that are currently available. Because proteinuria and albuminuria have numerous possible causes, they must be assessed appropriately to determine their implications for the patient. This assessment involves localization of the origin of the proteinuria as well as determination of its persistence and magnitude. Because persistent renal proteinuria usually indicates presence of chronic kidney disease, which sometimes is a progressive disorder, its detection identifies dogs and cats that have increased risk for adverse health outcomes. Thus, urine testing that will detect proteinuria should be a component of the clinical evaluations of dogs and cats under all circumstances that prompt their veterinarians to also perform comprehensive hematologic and serum biochemical evaluations. At a minimum, this testing should consist of a complete urinalysis that includes a satisfactorily accurate semiquantitative test for protein, and positive reactions should be properly followed with further testing. The appropriate response to persistent renal proteinuria depends on the magnitude of proteinuria and the status of the patient. The recommended response generally involves continued monitoring, further investigation, and therapeutic intervention, which should be implemented as an escalating series of inclusive, stepwise responses. |
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Vet Clin North Am Small Anim Pract. 2005 May;35(3):581-96. Early detection of renal damage and disease in dogs and cats. Grauer GF., Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, 111B Mosier Hall, Manhattan, KS 66506, USA. ggrauer@su.edu Renal damage and disease can be caused by acute or chronic insults to the kidney. Acute renal damage often results from ischemic or toxic insults and usually affects the tubular portion of the nephron. In contrast, chronic renal disease can be caused by diseases and/or disorders that affect any portion of the nephron, including its blood supply and supporting interstitium.Early detection of acute renal disease facilitates appropriate intervention that can arrest or at least attenuate tubular cell damage and the development of established acute renal failure. Similarly,early detection of chronic renal disease, before the onset of renal azotemia and chronic renal failure, should facilitate appropriate intervention that stabilizes renal function or at least slows its progressive decline. PMID: 15833560 [PubMed - indexed for MEDLINE] |
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Assessment and management of proteinuria in dogs and cats: 2004 ACVIM Forum Consensus Statement (small animal). Lees GE, Brown SA, Elliott J, Grauer GE, Vaden SL; American College of Veterinary Internal Medicine., Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474, USA. glees@cvm.tamu.edu Emerging data indicate that more attention should be given to the detection, evaluation, monitoring, and treatment of dogs and cats with proteinuria. The purposes of this consensus statement are to describe an appropriate approach for accomplishing these tasks and to provide specific recommendations for assessing and managing dogs and cats with proteinuria based on data that are currently available. Because proteinuria and albuminuria have numerous possible causes, they must be assessed appropriately to determine their implications for the patient. This assessment involves localization of the origin of the proteinuria as well as determination of its persistence and magnitude. Because persistent renal proteinuria usually indicates presence of chronic kidney disease, which sometimes is a progressive disorder, its detection identifies dogs and cats that have increased risk for adverse health outcomes. Thus, urine testing that will detect proteinuria should be a component of the clinical evaluations of dogs and cats under all circumstances that prompt their veterinarians to also perform comprehensive hematologic and serum biochemical evaluations. At a minimum, this testing should consist of a complete urinalysis that includes a satisfactorily accurate semiquantitative test for protein, and positive reactions should be properly followed with further testing. The appropriate response to persistent renal proteinuria depends on the magnitude of proteinuria and the status of the patient. The recommended response generally involves continued monitoring, further investigation, and therapeutic intervention, which should be implemented as an escalating series of inclusive, stepwise responses. PMID: 15954557 [PubMed - indexed for MEDLINE] |
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Vet Clin North Am Small Anim Pract. 2004 Jul;34(4):867-85, v. Early diagnosis of renal disease and renal failure. Lees GE, Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, 4474 TAMU, College Station, TX 77843-4474, USA. glees@cvm.tamu.edu The main goal of early diagnosis of renal disease and renal failure in dogs and cats is to enable timely application of therapeutic interventions that may slow or halt disease progression. Strategies for early diagnosis of renal disease use urine tests that detect proteinuria that is a manifestation of altered glomerular permselectivity or impaired urine-concentrating ability as well blood tests to evaluate plasma creatinine concentration. Animals with progressive renal disease should be carefully investigated and treated appropriately.Animals with mild, possibly nonprogressive, renal disease should be monitored adequately to detect any worsening trends,which should lead to further investigation and treatment even if the increments of change are small. PMID: 15223206 [PubMed - indexed for MEDLINE] |
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J Vet Pharmacol Ther. 2003 Jun;26(3):213-24.Click here to read Pharmacokinetic/pharmacodynamic modelling of the disposition and effect of benazepril and benazeprilat in cats. King JN, Maurer M, Toutain PL. Novartis Animal Health Inc., CH-4002, Basel, Switzerland. jonathan.king@ah.novartis.com The disposition and effect of benazepril and its active metabolite, benazeprilat, were evaluated in cats using a pharmacokinetic/pharmacodynamic model. Cats received single 1 mg/kg doses of intravenous 14C-benazeprilat and oral 14C-benazepril.HCl, and single and repeat (eight daily) oral administrations of 0.25, 0.5 and 1.0 mg/kg nonlabelled benazepril.HCl. The pharmacokinetic endpoints were plasma concentrations of benazepril and benazeprilat, and recovery of radioactivity in faeces and urine. The pharmacodynamic endpoint was plasma angiotensin-converting enzyme (ACE) activity. Benazeprilat data were fitted to an equation corresponding to a single-compartment model with a volume equal to the blood space (Vc = 0.093 L/kg). Within this space, benazeprilat was bound nonlinearly to ACE, which was mainly tissular (89.4%) rather than circulating (10.6%). Free benazeprilat was eliminated quickly from the central compartment (t1/2 approximately 1.0 h; Cl approximately 0.125 L/kg/h), elimination being principally biliary ( approximately 85%) rather than urinary ( approximately 15%). Nevertheless, inhibition of ACE was long-lasting (t1/2 16-23 h) due to high affinity binding of benazeprilat to ACE (Kd approximately 3.5 mmol/L, IC50 approximately 4.3 mmol/L). Simulations using the model predict a lack of proportionality between dose of benazepril, plasma benazeprilat concentrations and effect due to the nonlinear binding of benazeprilat to ACE. For example, increasing the dose of benazepril (e.g. above 0.125 mg/kg q24 h) produced only small incremental inhibition of ACE (either peak effect or duration of action). |
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EFFECT OF BENAZEPRIL IN CHRONIC RENAL INSUFFICIENCY IN CATS: INTERIM RESULTS FROM THE BENRIC CLINICAL TRIAL Presented to World Small Animal Veterinary Association 27th Congress (2002) J.N.King, A.Font for the BENRIC Study Group Objectives Materials & Methods Results Conclusions References Maschio G, Alberti D, Janin G, et al. Effect of angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996; 334: 939-945. |
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J Vet Pharmacol Ther. 2002 Oct;25(5):371-8. Effect of renal insufficiency on the pharmacokinetics and pharmacodynamics of benazepril in cats. King JN, Strehlau G, Wernsing J, Brown SA. Novartis Animal Health Inc., Basel, Switzerland. jonathan.king@ah.novartis.com 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. |
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Effect of Benazepril Treatment in Dogs with Naturally Occurring Chronic Renal Insufficiency Jean-Pierre
Cotard, DVM, PhD, Diplomate ECVIM-CA Benazepril has been shown to have beneficial effects in chronic renal insufficiency (CRI) in man; prolonging survival time and reducing urinary loss of protein (1). We tested the efficacy of benazepril in dogs with CRI. A total of 41 dogs with CRI were randomised to receive benazepril at a dose of 0.25-0.5 mg/kg or matched placebo once daily in a double-blinded clinical trial. Inclusion criteria were CRI of renal origin with plasma creatinine > 142 µmol/l and urine specific gravity < 1.020. The two groups were matched at baseline. During the trial, benazepril-treated dogs had lower protein in the urine, higher scores for appetite and general clinical condition, and lower loss of body weight as compared to the placebo-group. Differences reached statistical significance (p < 0.05) for urine protein and appetite. The mean survival time in the benazepril group was longer (290 days) than in the placebo group (236 days), although differences did not reach statistical significance (p=0.26). These interim results suggest, that as in man, benazepril may have beneficial effects in dogs with chronic renal insufficiency. Reference 1. Maschio et al. N Eng J Med 1996; 334: 939-945 |
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J Vet Pharmacol Ther 2002 Oct;25(5):371-8 Related Articles, Links Effect of renal insufficiency on the pharmacokinetics and pharmacodynamics of benazepril in cats. King JN, Strehlau G, Wernsing J, Brown SA. 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. Publication Types: PMID: 12423228 [PubMed - indexed for MEDLINE] |
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American Journal of Veterinary Research, March 2001, Vol. 62, No. 3, Pages 375-383, doi: 10.2460/ajvr.2001.62.375 Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency Scott A. Brown , VMD, PhD Cathy A. Brown , VMD, PhD Gilbert Jacobs , DVM
Jean Stiles , DVM, MS Rim S. Hendi , Objective—To determine effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. Animals—32 cats. Procedure—Renal mass was surgically reduced, and cats were assigned to 1 of 4 eight-cat groups. Group 1 received placebo, whereas groups 2, 3, and 4 received benazepril hydrochloride orally once daily for approximately 6.5 months at the following doses: group 2, 0.25 to 0.50 mg/kg of body weight; group 3, 0.50 to 1.00 mg/kg; and group 4, 1.00 to 2.00 mg/kg. Arterial blood pressures, glomerular filtration rate (GFR), and renal plasma flow were determined before treatment and during the treatment period. Other determinants of renal hemodynamics were measured by use of micropuncture techniques. Renal biopsy specimens were examined microscopically. Results—Compared with cats that received placebo, mean systolic arterial blood pressure was significantly less and GFR significantly greater in cats that received benazepril. Glomerular capillary pressure and the ratio of efferent to afferent arteriolar vascular resistance were also significantly less in treated cats. However, histologic differences in renal specimens were not detected. Conclusions and Clinical Relevance—Treatment with benazepril sustained single nephron GFR in remnant nephrons of cats with induced renal insufficiency. Administration of benazepril was also associated with a small but significant reduction in degree of systemic hypertension and an increase in whole kidney GFR. Benazepril may be an effective treatment to slow the rate of progression of renal failure in cats with renal disease. (Am J Vet Res 2001;62:375–383) |
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Alison Gledhill for the BENRIC (BENazepril in Renal Insufficiency in Cats) Study Group. Angiotensin converning enzyme inhibition and progressive renal insufficiency; a clinical trial in naturally occurring renal insufficiency in the cat. 2001 |
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J Pharmacol Exp Ther 2000 Mar;292(3):1094-103 Related Articles, Links New insights on effect of kidney insufficiency on disposition of angiotensin-converting enzyme inhibitors: case of enalapril and benazepril in dogs. Toutain PL, Lefebvre HP, Laroute V. Ecole Nationale Veterinaire de Toulouse, et Institut National de la Recherche Agronomique, Unite Associee de Physiopathologie et Toxicologie Experimentales, Toulouse, France. pl.toutain@envt.fr 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. PMID: 10688628 [PubMed - indexed for MEDLINE] |
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J Vet Intern Med 2000 Sep-Oct;14(5):526- Grauer GF, Greco DS, Getzy DM, Cowgill LD, Vaden SL, Chew DJ, Polzin DJ,
Barsanti JA. A blinded, multicenter, prospective clinical trial assessed the effects of enalapril (EN) versus standard care in dogs with naturally occurring, idiopathic glomerulonephritis (GN). Twenty-nine adult dogs with membranous (n = 16) and membranoproliferative (n = 13) GN were studied. Dogs were randomly assigned to receive either EN (0.5 mg/kg PO q12-24h; n = 16) or placebo (n = 14) for 6 months (1 dog was treated first with the placebo and then with EN). All dogs were treated with low-dose aspirin (0.5-5 mg/kg PO q12-24h) and fed a commercial diet. At baseline, serum creatinine (SrCr), systolic blood pressure (SBP), and glomerular histologic grade were not different between groups, but the urine protein/creatinine ratio (UP/C) was greater in the EN group compared with the placebo group (8.7 +/- 4.4 versus 4.7 +/- 2.3). After 6 months of treatment, the change in UP/C from baseline was significantly different between groups (EN = -4.2 +/- 1.4 versus 1.9 +/- 0.9 in the placebo group). When data were adjusted for changes in SrCr (SrCr X UP/C) a similar significant reduction was noted ( 2.2 +/- 15.2 versus 8.4 +/- 10.1). The change in SBP after 6 months of treatment also was significantly different between groups (EN = -12.8 +/- 27.3 versus 5.9 +/- 21.5 mm Hg in the placebo group). Response to treatment was categorized as improvement (assigned a value of 2), no progression (assigned a value of 1), and progression (assigned a value of 0). Response was significantly better in the EN group (1.4 +/- 0.8) compared with the placebo group (0.3 +/- 0.5). These results suggest that EN treatment is beneficial in dogs with naturally occurring idiopathic GN. PMID: 11012117 [PubMed - indexed for MEDLINE] |
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Journal of Veterinary Pharmacology & Therapeutics,
Volume 22, Number 6, December 1999 , pp. 360-367(8) Plasma angiotensin converting enzyme activity and pharmacokinetics of benazepril and benazeprilat in cats after single and repeated oral administration of benazepril.HCl Authors: King1; Humbert-Droz2; Maurer3 Abstract: After single administration of benazepril.HCl, maximum benazepril concentrations were recorded at the first sample (2 h) and declined relatively rapidly with an elimination half life (t½) of 1.4 h. Highest benazeprilat concentrations were recorded at the first sample (2 h) in most cats and declined biphasically with half lives of each phase of 2.4 and 27.7 h. With repeated administration, plasma benazeprilat concentrations accumulated slightly with accumulation ratios (R) of 1.46, 1.36 and 1.24 for the 0.25, 0.5 and 1.0 mg/kg dosages of benazepril.HCl, respectively (median value of 1.36 for all dosages). All three dosages of benazepril.HCl caused marked inhibition of plasma ACE activity in all cats. The maximum effect (Emax, % inhibition of ACE as compared to baseline) was ??98% after single and 100% with repeated administration. The duration of action of benazepril.HCl was long, with >?87% (single) and >?90% (repeat) inhibition of plasma ACE persisting 24 h after dosing. Benazepril.HCl was well tolerated in all animals. Dosages of 0.25-1.0 mg/kg benazepril.HCl once daily are recommended for clinical testing in cats. Document Type: Research article DOI: 10.1046/j.1365-2885.1999.00230.x Affiliations: 1: Novartis Animal Health Inc, Basel, Switzerland, 2: Novartis Animal Health Inc, Centre de Researche Santé Animale S.A., CH-1566, St Aubin, Switzerland, 3: Novartis Animal Health Inc, Centre de Researche Santé Animale S.A., CH-1566, St Aubin, Switzerland |
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Am J Vet Res 1999 Dec;60(12):1516-25 Related Articles, Links Effect of enalapril on blood pressure, renal function, and the renin-angiotensin-aldosterone system in cats with autosomal dominant polycystic kidney disease. Miller RH, Lehmkuhl LB, Smeak DD, DiBartola SP, Radin J. OBJECTIVE: To evaluate blood pressure, renal function, and the renin-angiotensin-aldosterone system (RAAS) in cats with autosomal dominant polycystic kidney disease (ADPKD) and to assess the effect of enalapril on these variables. ANIMALS: 6 cats with ADPKD and 6 age-matched healthy cats. PROCEDURE: To measure blood pressure and heart rate, a radiotelemetry catheter was placed in the left femoral artery of each cat. Baseline data collection included 24-hour blood pressure, heart rate, and motor activity. Blood was then collected for analysis of RAAS status and renal function. Enalapril (0.5 mg/kg of body weight, p.o., q 24 h) was administered for 1 week, and data collection was repeated. RESULTS: Differences in baseline blood pressure, heart rate, motor activity, RAAS status, and renal function were not detected between cats with ADPKD and control cats. Hypertension was not documented in cats with ADPKD. Blood pressure was significantly reduced for 15 to 17 hours after treatment with enalapril in both groups. Administration of enalapril also resulted in significant increases in plasma renin activity and significant decreases in angiotensin converting enzyme activity and atrial natriuretic peptide concentration but only minimal changes in glomerular filtration rate and effective renal plasma flow in both groups of cats. CONCLUSIONS AND CLINICAL RELEVANCE: Although hypertension is common in humans with ADPKD, cats with ADPKD were normotensive. Treatment with enalapril (0.5 mg/kg, p.o., q 24 h) significantly reduced blood pressure in normotensive healthy cats and cats with ADPKD, and resulted in predictable changes in RAAS enzyme activities and hormone concentrations. Enalapril had minimal effects on renal function. Publication Types: PMID: 10622161 [PubMed - indexed for MEDLINE] |
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Amberger CN, Glarden O, Glaus T, Hörauf A, King JN, Schmidli H, Schröter L & Lombard CW. (1999) Effects of benazepril in treatment of feline hypertropic cardiolmyopathy. Results of a prospective, open-label, multi-center clinical trial. Journal of Veterinary Cardiology. 1, 19-26, May 1999. |
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J Vet Intern Med 1999 Jan-Feb;13(1):21-7 Effects of renal impairment on the disposition of orally administered enalapril, benazepril, and their active metabolites. Lefebvre HP, Laroute V, Concordet D, Toutain PL. The pharmacokinetics of benazepril, enalapril, and their active metabolites (benazeprilat and enalaprilat) were compared after a single administration of each product by the oral route at the recommended dosage (0.5 mg/kg for both drugs) in the dog before and after moderate experimental renal impairment. Ten dogs were randomly assigned to 2 groups of 5 animals in a 2-period crossover design for angiotensin-converting enzyme inhibitor administration. Renal failure was surgically induced by right nephrectomy and electrocoagulation of the remaining kidney. Renal mass reduction induced a significant decrease (P < .001) in glomerular filtration rate (GFR) (1.7 +/- 0.3 versus 3.3 +/- 0.7 mL/kg/minute). No significant differences before and after surgery were observed for enalapril and benazepril kinetics. The area under the curve (AUC) for enalaprilat increased after surgery from 23.6 +/- 14.7 to 42.4 +/- 20.9 micrograms.minute/mL (P < .01). Mean peak plasma concentration (Cmax) was increased in the impaired dogs (59.1 +/- 23.3 versus 43.9 +/- 32.9 ng/mL), but this variation was not significant (P > .05). Renal failure had no significant effect on AUC for benazeprilat (13.8 +/- 9.8 versus 14.9 +/- 5.0 micrograms.minute/mL) (P > .05), but Cmax decreased significantly (from 55.0 +/- 26.4 to 31.9 +/- 17.7 ng/mL) (P < .05). Multiple regression analysis showed that both GFR and AUC for enalapril were highly significant variables that explained the variation in AUC for enalaprilat (R2 = .86, P < .001) but not for benazeprilat (R2 = .12, P > .05). The results of this study indicate that exposure to enalaprilat, but not to benazeprilat, is increased in dogs with subclinical renal impairment. PMID: 10052059 [PubMed - indexed for MEDLINE] |
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N Engl J Med. 1996 Apr 11;334(15):939-45. Comment in: Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. [Editor's Note: This paper concerns use of benazepril in humans. It was ground-breaking research - there's considerably more research now that posits that benazepril (and enalapril) " ... provides protection against the progression of renal insufficiency in patients with various renal diseases." The complete article can be viewed here.] The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group - Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P., Divisione di Nefrologia, Ospedale Civile, Verona, Italy. BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases. |
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Arzneimittelforschung 1991 Sep;41(9):913-23 Related Articles, Links General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on cardiovascular, visceral and renal functions and on hemodynamics. Yamamoto S, Takemori E, Hasegawa Y, Kuroda K, Nakao K, Inukai T, Sakonjyo
H, Nishimura T, Nishimori T. The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, on cardiovascular, visceral and renal functions and on hemodynamics, were studied in various experimental animals. Even at a high dose of 100 mg/kg p.o. benazepirl hydrochloride had no influence on the respiration, heart rate and ECG of normotensive anesthetized cats and, except at higher doses, had little effect on the contractile tension of mammalian isolated atrium, ileum, trachea, stomach fundus strips, vas deferens or uterus. Benazepril hydrochloride even at a high dose of 100 mg/kg p.o. had little effect on spontaneous uterine motility, charcoal transportation and gastrointestinal tract motility. In addition, it did not cause gastric irritation, alter the secretion of gastric and biliary juices, and did not affect the tension of the nictitating membrane or the twitch tension of the gastrocnemius muscle in various experimental animals. Benazepril hydrochloride had no effect on the blood glucose and cholesterol levels in alloxan-induced diabetic rats but decreased the triglyceride and total cholesterol levels in normotensive rats at a dose of 30 mg/kg p.o. Benazepril hydrochloride at 3 mg/kg.day s.c. for 10 weeks caused a significant decrease in aortic atherosclerosis without reducing hypercholesterolemia in cholesterol-fed rabbits. Benazepril hydrochloride at a high dose of 100 mg/kg p.o. showed no effect on the urine volume and urinary excretion of electrolytes but decreased PSP excretion in normotensive rats. At a dose of 3 or 10 mg/kg.day p.o. for 4 weeks benazepril hydrochloride inhibited the increase in the excretion of urinary protein in DOCA/salt spontaneously hypertensive rats. It caused hemolysis at concentrations as high as 0.1-1% in rabbits, however, even at a high dose of 100 mg/kg p.o. it did not affect red blood cell fragility in rats, and, except at a high dose of 10(-4) g/ml, showed little effect on the platelet aggregation response induced by collagen or arachidonic acid in rabbits. From these results, benazepril hydrochloride is considered to be a safe and well-tolerated addition to the therapeutic armamentarium of cardiovascular drugs. PMID: 1796919 [PubMed - indexed for MEDLINE] |
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Arch Int Pharmacodyn Ther 1988 Nov-Dec;296:131-43 Related Articles, Links Renal actions of the new angiotensin-converting enzyme inhibitor
benazepril hydrochloride. Research Department, Ciba-Geigy Corporation, Summit, NJ 07901. Renal actions of the new angiotensin-converting enzyme inhibitor benazepril hydrochloride were evaluated in comparison to enalapril in the anesthetized dog. Intravenous injection of either 0.4 mg/kg benazepril hydrochloride or enalapril significantly reduced mean arterial pressure (MAP) and significantly increased renal blood flow and glomerular filtration rate over a 2 hr period. Urine volume and sodium excretion increased, while urine osmolality decreased following i.v. injection of either benazepril hydrochloride or enalapril. The results presented in this study demonstrate that the new and structurally novel converting enzyme inhibitor benazepril hydrochloride has potent actions on renal function which are essentially identical to those of enalapril. PMID: 2853611 [PubMed - indexed for MEDLINE] |
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This web site is a product of me, David Jacobson. Its purpose is to make information on using benazepril and other ace inhibitors to treat feline CRF readily available to cat owners and veterinarians. I am not endorsing or advocating the use of benazepril for treating feline CRF. Please email me with your comments, criticisms and suggestions. |
