Comparative effects of antihypertensives on proteinuria: angiotensin-converting enzyme inhibitor versus alpha 1-antagonist.
Control of hypertension improves the course of renal disease. We compared the renal hemodynamic and permselective responses to an angiotensin-converting enzyme inhibitor (CEI) (enalapril) and an alpha 1-antagonist (prazosin) in 14 patients with established glomerular disease. A single-blinded, randomized, cross-over design was used consisting of a 3-week baseline period followed by two 4-week treatment periods, which were separated by a 4-week washout period. During the treatment periods, the CEI or alpha 1-antagonist was added to the patients' baseline antihypertensive medications. Mean arterial pressure (MAP) was reduced to similar levels by both drugs, although the time-averaged blood pressure throughout the study was higher with the alpha 1-antagonist. Twenty-four-hour urinary protein, albumin, and IgG excretion were not significantly different at the end of the CEI and alpha 1-antagonist periods. However, compared with baseline values, significant decreases in total protein and IgG excretion occurred only during the CEI period, while albumin excretion decreased with both drugs. A 22% decrease in the fractional clearance of albumin (4.95 +/- 1.44 to 3.88 +/- 1.57 x 10(-3); P less than 0.01) and a 49% decrease in the fractional clearance of IgG (1.58 +/- 0.42 to 0.81 +/- 0.28 x 10(-3); P less than 0.001) occurred during CEI therapy with no significant changes in these parameters being seen with alpha 1-antagonist therapy (albumin: 4.95 +/- 1.44 to 4.48 +/- 1.51 x 10(-3), P = NS; IgG: 1.58 +/- 0.42 to 1.71 +/- 0.70 x 10(-3), P = NS). At the time of the fractional clearance measurements, MAP proved to be lower on the CEI. Reanalysis of the data for the subgroup of 11 patients without differences in MAP during the clearance period demonstrated a beneficial effect favoring CEI. Except for the greatest decreases in blood pressure (21 to 30 mm Hg), a greater antiproteinuric effect for a given decrease in blood pressure was seen with the CEI. Additionally, reduction in proteinuria occurred in a subset of seven patients whose baseline MAP was in the normotensive range. In conclusion, lowering MAP improves proteinuria. CEI appears to exert a more favourable effect even at similar MAP. Reductions in blood pressure, even within the accepted normal range, lessen permselective defects.
Rosenberg
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ME
Department of Medicine, University of Minnesota, Minneapolis 55455.
Hostetter
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TH
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000201:enzymology / Q000503:physiopathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011224:Prazosin / Q000627:therapeutic use*; D011507:Proteinuria; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D016037:Single-Blind Method
D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D011224:Prazosin