Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study (original) (raw)
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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.
Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic
2000
In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning
Background: Inhibition of the renin-angiotensin system in patients with diabetic nephropathy can reduce proteinuria and slow down renal impairment. In this study, we aimed to evaluate the preventive effects of prescribing both angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor inhibitors (ARBs) for renal disease progression compared with administrating each of these two medications alone in patients with type 2 diabetes. Methods: 90 patients with diabetic nephropathy were randomized into three groups: receiving captopril, losartan, and losartan in combination with captopril. Proteinuria was measured before, 2, 6 and 12 months after intervention, and creatinine clearance was measured before and after intervention. Repeated measures ANOVA, Fisher's least significant difference (Fisher's LSD), and t-test were used for data analysis by SPSS software. Findings: Proteinuria was improved in all groups who received medication (P < 0.001). This reduction in the group who received losartan in combined to captopril was more than other groups (P = 0.026). Creatinine clearance was not significantly different between all groups. Conclusion: Administration of ACEI or ARBs reduced proteinuria in patients suffering from diabetic nephropathy (due to type 2 diabetes) but prescribing both drugs had a significantly better outcome. However, creatinine clearance was not significantly improved in any of the groups. Keywords: Diabetes mellitus, Angiotensin-converting enzyme inhibitors, Angiotensin receptor antagonists, Proteinuria
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.
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.
Angiotensin-Receptor Blockade versus Converting–Enzyme Inhibition in Type 2 Diabetes and Nephropathy
New England Journal of Medicine, 2005
Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes. methods In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes.
Nephrology Dialysis Transplantation, 2001
Background. The aim of the present study was to investigate the effect of losartan on the progression of renal function in non-diabetic patients with chronic renal failure in an open, prospective, follow-up study of 1 year. Methods. Twenty-nine hypertensive patients (14 females and 15 males; mean age 63 years.) with non-diabetic chronic renal failure of several causes received losartan 50 mguday (plus other antihypertensive agents if needed) and were followed-up prospectively during 13"1 months. Eighteen patients received angiotensin-converting enzyme inhibitors plus other antihypertensive drugs at baseline. Patients had been followed-up for 44"4 months prior to the treatment with losartan. The rate of progression of renal insuf-®ciency was evaluated as the slope of the reciprocal of serum creatinine vs time in months.
Renal and Cardiovascular Protection in Type 2 Diabetes Mellitus: Angiotensin II Receptor Blockers
Journal of the American Society of Nephrology, 2002
ABSTRACT. Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the developm...