Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor therapy

Abstract Background: Angiotensin-converting enzyme (ACE) inhibitors effectively reduce proteinuria; however, the optimal antiproteinuric dose is still unknown. We conducted this study to determine whether an increase in ACE-inhibitor dose above the maximal antihypertensive effect has additional antiproteinuric potential. Methods: Twenty-three proteinuric patients were administered the ACE inhibitor spirapril at a starting dose of 3 to 6 mg/d. The dose was increased every 6 weeks until the maximal antihypertensive effect, assessed by 24-hour ambulatory blood pressure (ABP) monitoring, was achieved (spir max ), then increased to a supramaximal dose (spir supramax ). Renal parameters, urinary protein excretion, and systemic activity of the renin-angiotensin system were compared between baseline, spir max , and spir supramax . Glomerular filtration rate and renal plasma flow were determined before the administration of spirapril and after administration of the supramaximal dose. Results: Median ABP and proteinuria decreased significantly between baseline and spir max (median, 102 mm Hg; range, 82 to 122 mm Hg versus 97 mm Hg; range, 82 to 113 mm Hg; median protein, 2.56 g/d; range, 1.05 to 22.1 g/d versus 1.73 g/d; range, 0.42 to 4.7 g/d). Both creatinine level and creatinine clearance remained unchanged. Suppression of angiotensin II formation led to a significant increase in renin and angiotensin I concentrations and a nonsignificant decrease in aldosterone levels. The increase in spirapril to a supramaximal dose had no further effect on serum renin or angiotensin I levels or proteinuria. There was an additional slight decrease in aldosterone levels and, subsequently, a significantly lower level than at baseline. Conclusion: Our results show that the antiproteinuric effect of spirapril is associated with its antihypertensive effect. Although high-dose ACE-inhibitor therapy has no additional influence on proteinuria, a possible beneficial long-term effect cannot be ruled out. © 2002 by the National Kidney Foundation, Inc.