Influence of Ramipril on Renal Function in Patients with Chronic Congestive Heart Failure

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Ramipril was administered to 13 patients, aged 49–80 years, weighing 53.5–90.3 kg, with congestive heart failure (CHF) for 2 weeks in an open trial. One patient dropped out after day I and another accidentally received another angiotensin-converting enzyme (ACE) inhibitor, so that 11 patients remained for analysis. Each patient received 5 mg of ramipril daily for 2 weeks, followed by a 1-week washout period. Urine was collected in 4-h fractions for 12 h followed by a 12-h fraction on days 1, 8, and 15. Creatinine clearance, as well as the excretion of albumin and the urinary brush border enzymes γ-glutamyl transferase (GGT), alanine aminopeptidase (AAP). N-acetyl-β-D-glucosaminidase (NAG), and lactate dehydrogenase (LDH) were determined. The values for albumin excretion, creatinine clearance. GGT, AAP, NAG, and LDH obtained for the various days during the time course before and during multiple dosing were subjected to an analysis of variance followed by Scheffe's test for means. Daily albumin excretion decreased during treatment with ramipril from 23.8 ± 27.4 mg/24 h (baseline) to 12.9 ± 15.1 (day 1), 10.8 ± 15.6 (day 8), and 12.4 ± 12.7 mg/24 h (day 15). The differences were significant (α = 0.05) when compared to pretreatment albumin excretion. Creatinine clearance increased from 78.8 ± 38.3 ml/min (baseline) to 82.4 ± 34.6 (day 1), 85.1 ± 28.5 (day 8), and 91.7 ± 36.4 ml/min (day 15). The change on day 15 was significant (α = 0.05) when compared to pretreatment values. The excretion of GGT, AAP, and NAG in urine remained unchanged during 15 days of ramipril treatment, whereas the excretion of LDH decreased from 12.8 ± 9.0 U/24 h (baseline) to 6.0 ± 4.4 (day 1), 7.2 ± 3.5 (day 8), and 4.7 ± 3.7 U/24 h (day 15). The differences compared to the pretreatment values were significant (α = 0.05). Ramipril exhibited a nephroprotective effect by decreasing albumin excretion and increasing creatinine clearance in patients suffering from chronic CHF, as has been demonstrated for diabetics and patients with renal insufficiency.

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