Comparative Effects of Antihypertensives on Proteinuria: Angiotensin-Converting Enzyme Inhibitor Versus α₁-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 α₁-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 α₁-antagonist was added to the patients' baseline anti hypertensive 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 α₁-antagonist. Twenty-four-hour urinary protein, albumin, and IgG excretion were not significantly different at the end of the CEI and α₁-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 × 10^-3; P < 0.01) and a 49% decrease in the fractional clearance of IgG (1.58 ± 0.42 to 0.81 ± 0.28 × 10^-3; P < 0.001) occurred during CEI therapy with no significant changes in these paramaters being seen with α₁-antagonist therapy (albumin: 4.95 ± 1.44 to 4.48 ± 1.51 × 10^-3, P = NS; IgG:1.58 ± 0.42 to 1.71 ± 0.70 × 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.