Clinical Investigation

Kidney International (1994) 45, 861–867; doi:10.1038/ki.1994.113

Is the antiproteinuric effect of ACE inhibition mediated by intereference in the renin-angiotensin system?

Ron T Gansevoort1, Dick de Zeeuw1 and Paul E de Jong1

1Department of Medicine, Division of Nephrology, State University Hospital, Groningen, The Netherlands

Correspondence: D de Zeeuw MD, Department of Medicine, State University Hospital, Oostersingel 59, 9713 EZ Groningen, The Netherlands.

Received 17 August 1993; Revised 22 October 1993; Accepted 25 October 1993.

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Abstract

Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system? Angiotensin converting enzyme (ACE) inhibition causes specific renal effects, such as a rise in effective renal plasma flow, a fall in filtration fraction and a lowering of proteinuria. The mechanism of these renal effects is still debated. Recent animal studies suggest that non-angiotensin (Ang) II related actions of ACE inhibition, such as bradykinin accumulation, may have a role. We therefore investigated the effects of specific intervention in the renin-angiotensin system with the Ang II receptor antagonist losartan, and compared these effects to those obtained with ACE inhibition, as this comparison might resolve the question whether or not the effects of ACE inhibition are Ang II related. The effects of losartan and enalapril were studied in eleven patients with non-diabetic proteinuria and hypertension. The protocol consisted of seven periods, each lasting one month, in which patients received once daily placebo, 50 mg losartan, 100 mg losartan, placebo, 10 mg enalapril, 20 mg enalapril, and placebo, respectively. At the end of each study period proteinuria, blood pressure, and renal function were determined. On both doses of losartan and enalapril proteinuria and blood pressure fell, whereas ERPF increased and GFR remained stable. The fall in urinary protein excretion was similar for both drugs: 46.3% (28.3% to 63.1%) on 100 mg losartan versus 51.6% (37.0% to 69.2%) on 20 mg enalapril (expressed as Wilcoxon-based estimated median with 95% CI). The same held true for the fall in blood pressure [15.1% (12.7% to 20.2%) vs. 17.3% (15.4% to 22.0%)], the rise in ERPF [13.3% (4.2% to 23.4%) vs. 13.1% (4.1% to 27.0%)] and the fall in FF [15.1% (5.7% to 20.6%) vs. 14.6% (4.7% to 22.7%)]. In conclusion, the Ang II receptor antagonist losartan induces changes in blood pressure, renal hemodynamics, and proteinuria similar to those induced by ACE inhibition. These data support the idea that the antiproteinuric effect of ACE inhibition, as well as the renal hemodynamic effects, are primarily mediated by interference in the renin-angiotensin system.

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