Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade


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Abstract

Background Limitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration.Objective To investigate whether, in hypertensive patients with glomerulonephritis, a combination of an angiotensin converting enzyme inhibitor (ACEI, fosinopril 20 mg/day) with an angiotensin receptor blocker (ARB, irbesartan 150 mg/day) produces a more profound antiproteinuric effect than either drug alone.Methods Ten non-diabetic patients with glomerulonephritis, normal or slightly reduced but stable renal function (creatinine clearance 40–106 ml/min) without immunosuppression were studied. Clinical evaluations, 24 h blood pressure measurements and laboratory tests were performed as follows: (1) without medication (baseline) and in random sequence; (2) ACEI alone; (3) ARB alone; and (4) combination of ACEI + ARB. Each period lasted for 6 weeks, separated by three washout periods of 4 weeks each without therapy.Results ACEI and ARB alone reduced proteinuria from 7.9 ± 7.1 to 5.3 ± 5.2 and 5.0 ± 4.9 g/24 h (mean ± SD), respectively. The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient (to 3.3 ± 3.7 g/24 h) than either drug alone (P = 0.039 by ANOVA). The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure (basal, 106 ± 8; ACEI, 97 ± 5; ARB, 98 ± 5; ACEI + ARB, 95 ± 5 mmHg) or creatinine clearance (basal, 77 ± 27; ACEI, 73 ± 31; ARB 80 ± 30; ACEI + ARB, 73 ± 32 ml/min).Conclusions A combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone. This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance. A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss.

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