The antiproteinuric effect of enalapril is potentiated by losartan in normotensive patients with diabetic nephropathy

Arteaga, Jesus; Petrina, E.; Anda, Emma; Calderón, Donatella Petrocelli; Sorbet, Maria; Asirón, M

doi:10.1016/s0895-7061(00)00550-1

Cited by 4 publications

(4 citation statements)

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“…There are several potential benefits of combined treatment with ACE inhibitors and AT 1 -RA in a patient with renal disease: enhanced blockade of RAS (e.g., an increase in plasma renin activity), no change or slight reduction in plasma aldosterone levels, increased renal plasma flow, preserved glomerular filtration rate, reduced proteinuria, and suppressed cytokine expression (e.g., tumor growth factor ␤ 1 ) (28,29).…”

Section: Discussionmentioning

confidence: 99%

Irbesartan Reduces the Albumin Excretion Rate in Microalbuminuric Type 2 Diabetic Patients Independently of Hypertension

et al. 2002

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OBJECTIVE -ACE inhibitors delay the progression from incipient to overt diabetic nephropathy and reduce albumin excretion rate (AER), independently of blood pressure. Angiotensin II type 1 receptor antagonists produce similar effects on microalbuminuria and mean arterial pressure. The aim of this study was to evaluate the effect of irbesartan on microalbuminuria and blood pressure in hypertensive and normotensive type 2 diabetic patients.RESEARCH DESIGN AND METHODS -Sixty-four microalbuminuric hypertensive (group 1) and 60 microalbuminuric normotensive (group 2) type 2 diabetic male patients, matched for age, BMI, HbA 1c , and diabetes duration, were enrolled. Each group was divided into two subgroups receiving either irbesartan (150 mg b.i.d. orally) or placebo for 60 days. After 15 days of washout, irbesartan was given to the subgroups who had received the placebo, and vice versa, in a randomized double-blind crossover study.RESULTS -In microalbuminuric hypertensive type 2 diabetic subjects, irbesartan reduced 24-h mean systolic and diastolic pressure and AER. In microalbuminuric normotensive type 2 diabetic patients, irbesartan reduced AER.CONCLUSIONS -These results indicate the beneficial effects of irbesartan on AER in type 2 diabetic subjects, independently of its antihypertensive effects. Diabetes Care 25:1909 -1913, 2002D iabetic nephropathy is the most common cause of renal failure in western society. Numerous factors predispose diabetic subjects to the development of renal disease. Hypertension is a major risk factor, and there is a direct correlation between glycemic control and the impairment of renal function (1). Thus, strategies for preventing the progression of renal failure in diabetic patients, particularly in the early phase of nephropathy, include blood pressure (BP) as well as glycemic control (2). Diabetic nephropathy develops gradually and slowly, finally leading to overt disease. The first indication of diabetic nephropathy is microalbuminuria, i.e., albumin excretion rate (AER) between 20 and 200 g/min, in at least two of three consecutive measurements. This condition is referred to as "incipient nephropathy." In both type 1 and type 2 diabetes, microalbuminuria is a predictor of persistent proteinuria and early death from cardiovascular disease (3).The renin angiotensin system (RAS) is considered to be a paracrine regulator of renal function and blood flow, thus playing an important role in the progression of chronic renal disease, as seen in diabetic nephropathy. The effects of blocking the RAS with ACE inhibitors on delay or prevention of incipient to overt nephropathy and renal failure are widely recognized (4).Experimental studies and clinical trials have demonstrated that ACE inhibitors lower microalbuminuria independently of BP control (5,6); thus, blocking RAS with ACE inhibitors is beneficial for hypertensive as well as normotensive microalbuminuric diabetic patients.ACE inhibitors are more effective than conventional antihypertensive agents because they can modify both systemic...

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Section: Discussionmentioning

confidence: 99%

Irbesartan Reduces the Albumin Excretion Rate in Microalbuminuric Type 2 Diabetic Patients Independently of Hypertension

et al. 2002

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“…199 The RAAS plays an important short-term role in the circulation through haemodynamic and renal effects while the long-term tissue effects are integral in multiple other functions and systems that regulate inflammation and cellular growth, such as fibrosis, Figure 6 The antiproteinuric effect of combining losartan (LOS; 50 mg) with an ACE-inhibitor (ACE-I) in eight normotensive, non-nephrotic proteinuria (1-3 g/day) patients with IgA nephropathy was compared to monotherapy. Urinary protein excretion was measured at the end of each four week period for ACE-I monotherapy, ACE-I + LOS combination therapy, LOS monotherapy and LOS + ACE-I combination therapy periods.Adapted from Russo et al 194 Table 6 Potential benefits of combination therapy (ACE-I + ARB) in renal disease patients 10,17,58,156,[193][194][195][196]…”

Section: Discussionmentioning

confidence: 99%

“…33,185 Clinical studies that have combined ACE-I and ARBs, have shown more complete inhibition of the RAAS, resulting in enhanced renal vasodilation and additional reductions in proteinuria (Table 6). 10,17,58,156,[193][194][195][196] In one study, when losartan (50 mg/day) was added to a moderate dose of an ACE-I in normotensive patients with IgA nephropathy, proteinuria was more profoundly reduced than with either agent alone (Figure 6). 194 Urinary protein excretion was reduced by 69% on combined ACE-I and ARB therapy compared with either drug as monotherapy (-39% on ACE-I; -27% on ARB).The additional effect on urinary protein excretion was not dependent on changes in systemic BP or glomerular filtration rate (GFR), but was secondary to the improvements of haemodynamics and/or membrane permeability at the glomerular level.…”

Section: Basic / Clinical Studiesmentioning

confidence: 99%

“…Enhanced blockade of the RAAS (e.g. increase in PRA) 20,191 No change or slight reduction in plasma aldosterone levels 20 Increased RPF 191 Preserved or no ∆ GFR 20,191 Reductions in proteinuria 157,195 Greater ability to suppress cytokine expression (e.g TGF-B 1 ) 13,59,193 RAAS = renin angiotensin-aldosterone system; PRA = plasma renin activity; RPF = renal plasma flow; GFR = glomerular filtration rate; TGF-B 1 = transforming growth factor beta-1…”

Section: Clinical Studiesmentioning

confidence: 99%

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Effectively targetting the renin-angiotensin-aldosterone system in cardiovascular and renal disease: rationale for using angiotensin II receptor blockers in combination with angiotensin-converting enzyme inhibitors

Weinberg

Zappe

2000

J Renin Angiotensin Aldosterone Syst

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Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy

Russo

Minutolo

Pisani

et al. 2001

American Journal of Kidney Diseases

221

187

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The antiproteinuric effect of enalapril is potentiated by losartan in normotensive patients with diabetic nephropathy

Cited by 4 publications

References 0 publications

Irbesartan Reduces the Albumin Excretion Rate in Microalbuminuric Type 2 Diabetic Patients Independently of Hypertension

Irbesartan Reduces the Albumin Excretion Rate in Microalbuminuric Type 2 Diabetic Patients Independently of Hypertension

Effectively targetting the renin-angiotensin-aldosterone system in cardiovascular and renal disease: rationale for using angiotensin II receptor blockers in combination with angiotensin-converting enzyme inhibitors

Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy

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