Dissociation between the course of the hemodynamic and antiproteinuric effects of angiotensin I converting enzyme inhibition

Abstract

Angiotensin I converting enzyme inhibition (ACEi) has been shown to lower urinary protein excretion in human renal disease. The mechanism of this antiproteinuric effect is hypothesized to be mediated by changes in renal hemodynamics. However, clinical studies suggest that the effect on renal hemodynamics is fully established immediately after the start of treatment, whereas others show the antiproteinuric effect to reach maximum only after several weeks. To clarify this issue we studied the course of renal hemodynamics, blood pressure and proteinuria during 28 days of ACEi (enalapril 10 mg oid) in nine patients with proteinuria due to non-diabetic renal disease. The effect of ACEi on blood pressure and renal hemodynamics was already maximal within a few hours after start of treatment, and remained stable thereafter: MAP was lowered with 8.6 ± 1.9%, 10.6 ± 2.1%, 12.8 ± 2.3% and 12.9 ± 2.5%, while FF fell 23.0 ± 2.0%, 17.0 ± 2.6%, 16.8 ± 2.8% and 15.9 ± 4.0% on days 1, 7, 14 and 28 of ACEi, respectively. However, the antiproteinuric effect only gradually reached its maximum on day 28. Urinary protein excretion decreased with 10.9 ± 6.1%, 32.7 ± 6.2%, 46.3 ± 2.5% and 54.0 ± 2.5% on days 1, 7, 14 and 28 of ACEi, respectively. After drug withdrawal all parameters returned towards baseline. We conclude that a dissociation occurs in the course of the ACEi induced effects on hemodynamics and urinary protein excretion. Although the short-term antiproteinuric effect of ACEi may be mediated through changes in systemic and renal hemodynamics, during continued ACEi-treatment the antiproteinuric effect appears to be at least partially mediated by other, non-hemodynamic mechanisms.