Combination Therapy of Angiotensin Converting Enzyme Inhibitor and Angiotensin AT1 Receptor Antagonist in Diabetic Nephropathy (original) (raw)
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International Journal of Pharmacy and Pharmaceutical Sciences, 2016
Objective: To observe the clinical outcomes on usage of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in type 2 diabetic nephropathy patients. Methods: A total 70 patients diagnosed with diabetic nephropathy were treated with ACEIs or ARBs were enrolled in this study. The data was collected from the out patients and the physician. A data collection form was used for collecting patient data. The form was used to record the details of patient's demographics, history of diabetes mellitus, duration of diabetes mellitus co morbidities, food habits and laboratory parameters such as serum creatinine, HbA1c and all the relevant things. The study has obtained ethical clearance from the institution ethics committee (IEC). Results: The study showed middle aged patients were more prone to diabetes and pre-existing hypertension is a major risk factor for diabetic nephropathy. Majority of the patients had long duration of diabetes mellitus which indicates the strong relation between duration of diabetes mellitus with diabetic nephropathy. Compared to ACE inhibitors, ARBs decreased the level of renal parameters. This reveals the better renoprotective effect of ARBs over ACE inhibitors. ARBs had more beneficial effects in reducing the major risk factor like proteinuria in diabetic nephropathy. A considerable reduction in HbA1c values were also observed in patients using ARBs. Conclusion: While comparing the improvement in proteinuria and the laboratory outcomes, ARBs were beneficial relatively to the ACEs in patients with diabetic nephropathy.
International Journal of Clinical Practice, 2004
The benefits of angiotensin-converting enzyme inhibitors and angiotensin II (ATII) receptor antagonist therapy of diabetic nephropathy (DNP) are thought to be largely the result of attenuation of ATII effects on proteinuria. The aim of the study was to ascertain whether there is the additive anti-proteinuric effect of enalapril plus losartan in DNP. Twenty-two patients with DNP were studied. Patients were randomly assigned to enalapril 10 mg/day (11 patients) or losartan 50 mg/day (11 patients) administered in a single oral dose in the morning for 12 weeks. and then, in 10 patients (five patients from enalapril group and five patients from losartan group), combination therapy (10 mg/day enalapril and 50 mg/day losartan) was started and continued for 12 weeks. In 12 patients, initial drugs dosages were doubled (six patients 20 mg/day enalapril and six patients 100 mg/day losartan), and monotherapy was continued for 12 weeks. Blood pressure and proteinuria were measured before and after therapy. Adverse effects were recorded at every visit. Proteinuria decreased by 33% with enalapril and losartan administered alone (p < 0.05). Co-administration of enalapril and losartan decreased proteinuria by a greater extent compared with enalapril and losartan administered alone (51%, p < 0.05). This proteinuria level was significantly lover than the proteinuria level of 12 weeks therapy with enalapril and losartan alone. The decrease of proteinuria was 37% in double-dose monotherapy group (p < 0.05). Reduction of mean arterial blood pressure (MAP) in co-administration of enalapril and losartan was higher than enalapril and losartan administered alone (p < 0.05). Combination of enalapril and losartan decreased proteinuria and MAP by a greater extent compared with enalapril and losartan administered alone. We have found that proteinuria reduction induced by combined therapy is maintained throughout short-term follow-up; a greater anti-proteinuric response was observed in the patients with DNP.
Diabetic Medicine, 2007
Aims Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) prevent the progression of diabetic nephropathy (DN). Studies suggest that combination renin–angiotensin–aldosterone system (RAAS)-inhibiting therapy provides additive benefit in DN. However, these studies are small in size. We performed a meta-analysis of studies investigating combination therapy for DN.Methods Studies were identified through a search of medline, embase, cinahl and the Cochrane Database. All trials involving combined ACEI and ARB for slowing progression of DN were included. The primary end point was 24-h urinary protein excretion. Blood pressure, serum potassium and glomerular filtration rate (GFR) were secondary end points.Results In the 10 included trials, 156 patients received ACEI + ARB and 159 received ACEI only. Most studies were 8–12 weeks in duration. Proteinuria was reduced with ACEI + ARB (P = 0.01). This was associated with significant statistical heterogeneity (P = 0.005). ACEI + ARB was associated with a reduction in GFR [3.87 ml/min (7.32–0.42); P = 0.03] and a trend towards an increase in serum creatinine (6.86 µmol/l 95% CI −0.76–13.73; P = 0.09). Potassium was increased by 0.2 (0.08–0.32) mmol/l (P < 0.01) with ACEI + ARB. Systolic and diastolic blood pressure were reduced by 5.2 (2.1–8.4) mmHg (P < 0.01) and 5.3 (2.2–8.4) mmHg (P < 0.01), respectively.Conclusions This meta-analysis suggests that ACEI + ARB reduces 24-h proteinuria to a greater extent than ACEI alone. This benefit is associated with small effects on GFR, serum creatinine, potassium and blood pressure. These results should be interpreted cautiously as most of the included studies were of short duration and the few long-term studies (12 months) have not demonstrated benefit.
International Journal of Pharmacy and Pharmaceutical Sciences, 2016
Objective : To observe the clinical outcomes on usage of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in type 2 diabetic nephropathy patients. Methods : A total 70 patients diagnosed with diabetic nephropathy were treated with ACEIs or ARBs were enrolled in this study. The data was collected from the out patients and the physician. A data collection form was used for collecting patient data. The form was used to record the details of patient’s demographics, history of diabetes mellitus, duration of diabetes mellitus co morbidities, food habits and laboratory parameters such as serum creatinine, HbA1c and all the relevant things. The study has obtained ethical clearance from the institution ethics committee (IEC). Results : The study showed middle aged patients were more prone to diabetes and pre-existing hypertension is a major risk factor for diabetic nephropathy. Majority of the patients had long duration of diabetes mellitus which indi...
American Journal of Kidney Diseases, 2013
Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers has been shown to lessen the rate of decrease in glomerular filtration rate in patients with diabetic nephropathy. A multicenter open-label randomized controlled trial to compare the efficacy of combining the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor blocker irbesartan with that of each drug in monotherapy (at both high and equipotent doses) in slowing the progression of type 2 diabetic nephropathy. 133 patients with type 2 diabetic nephropathy (age, 66 ± 8 years; 76% men) from 17 centers in Spain. Patients were randomly assigned (1:1:2) to lisinopril (n = 35), irbesartan (n = 28), or the combination of both (n = 70). The primary composite outcome was a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% increase in baseline serum creatinine level, end-stage renal disease, or death. Baseline values for mean estimated glomerular filtration rate and blood pressure were 49 ± 21 mL/min/1.73 m(2) and 153 ± 19/81 ± 11 mm Hg. Mean geometric baseline proteinuria was protein excretion of 1.32 (95% CI, 1.10-1.62) g/g creatinine. After a median follow-up of 32 months, 21 (30%) patients in the combination group, 10 (29%) in the lisinopril group, and 8 (29%) in the irbesartan group reached the primary outcome. HRs were 0.96 (95% CI, 0.44-2.05; P = 0.9) and 0.90 (95% CI, 0.39-2.02; P = 0.8) for the combination versus the lisinopril and irbesartan groups, respectively. There were no significant differences in proteinuria reduction or blood pressure control between groups. The number of adverse events, including hyperkalemia, was similar in all 3 groups. The study was not double blind. The sample size studied was small. We were unable to show a benefit of the combination of lisinopril and irbesartan compared to either agent alone at optimal high doses on the risk of progression of type 2 diabetic nephropathy.
Angiotensin receptor blockers in diabetic nephropathy: renal and cardiovascular end points
Seminars in Nephrology, 2004
The activity of the renin-angiotensin-aldosterone system (RAAS) is elevated both in the circulation and in the renal tissue of diabetic and nondiabetic nephropathies. The increased RAAS activity plays an important role in the hemodynamic and nonhemodynamic pathogenetic mechanisms involved in kidney disease. Previous studies have demonstrated that albuminuria is not only a marker of glomerular lesions, but also a progression promoter, and finally a powerful predictor of the long-term beneficial effect of blood pressure-lowering therapy. Randomized crossover and parallel blind studies in patients with diabetic nephropathy have demonstrated that angiotensin II receptor blockers (ARB) induce favorable changes in systemic blood pressure, renal hemodynamics, and proteinuria similar to those induced by angiotensin-converting enzyme (ACE) inhibition. Studies have revealed the optimal renoprotective dose for some ARBs; however, additional dose titration studies are urgently needed to obtain the maximum benefit of this valuable new class of compounds. The combination of ARB and ACE inhibition is well tolerated and even more effective than monotherapy in reducing systemic blood pressure and albuminuria in diabetic nephropathy. In addition, dual RAAS blockade is safe and well tolerated. Impaired autoregulation of glomerular filtration rate (GFR); demonstrated with some blood pressure-lowering agents implies disturbances in the downstream transmission of the systemic blood pressure into the glomerulus, leading to capillary hypertension or hypotension depending of the level of blood pressure. ARB does not interfere with GFR autoregulation in hypertensive diabetic patients. In contrast to previous observational studies with ACE inhibition, long-term treatment with ARB has similar beneficial renoprotective effect on progression of diabetic kidney disease in hypertensive diabetic patients with ACE II and DD genotypes. ARB can prevent/delay development of diabetic nephropathy independently of its beneficial blood pressure-lowering effect in patients with type 2 diabetes and microalbuminuria. Recently, two landmark studies led to the following conclusion: "Losartan and Irbesartan conferred significant renal benefit in patients with type 2 diabetes and nephropathy. This protection is independent of the reduction in blood pressure it causes. The ARB is generally safe and well tolerated." A recent metaanalysis indicates that ARBs reduce cardiovascular events mainly because of reduction in first hospitalization for congestive heart failure in hypertensive type 2 diabetic patients with albuminuria. The studies mentioned here suggest that ARB represents a beneficial treatment of hypertension and proteinuria in incipient and overt diabetic nephropathy.
Prevention and treatment of diabetic nephropathy
Diabetes Research and Clinical Practice, 2005
Objective: To discuss the role of angiotensin-converting enzyme inhibitors in the management of diabetesrelated renal disease. Methods: We review the published data from animal studies and clinical trials and outline the adverse effects that may limit the use of these drugs. Results: Diabetic nephropathy is the most common cause of end-stage renal disease and dialysis in the United States. With improving measures to optimize blood glucose control and blood pressure, the progression from mild proteinuria to overt renal insufficiency can now be retarded or even arrested. Studies of therapeutic interventions have shown that angiotensin-converting enzyme inhibitors have a superior beneficial effect on nephropathy. Few adverse effects are associated with use of these drugs: a nonproductive cough is the most frequent side effect, and angioedema and agranulocytosis are the most serious (albeit rarely reported) effects. Conclusion: Angiotensin-converting enzyme inhibitors should be considered as first-line therapy for patients with diabetes who have microalbuminuria or macroalbuminuria.