Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies

Kidney Int. 2003 Mar;63(3):1094-103. doi: 10.1046/j.1523-1755.2003.00832.x.


Background: Proteinuria predicts renal disease progression, and its reduction by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) is renoprotective.

Methods: In this prospective, randomized, cross-over study of 24 patients with nondiabetic, chronic nephropathies, we compared the effects on proteinuria, renal hemodynamics, and glomerular permselectivity of 8 weeks with comparable blood pressure control achieved by benazepril (10 mg/day) and valsartan (80 mg/day) combined therapy with those achieved by benazepril (20 mg/day) or valsartan (160 mg/day) alone.

Results: Despite comparable changes in blood pressure and glomerular filtration rate (GFR), combined therapy decreased proteinuria more than benazepril (-56% vs. -45.9%, P=0.02) and valsartan (-41.5%, P=0.002). Changes in urinary protein to creatinine ratio followed the same trend. Filtration fraction and renal vascular resistances (RVR) decreased more with combined (-14.7%,-23.7%) or benazepril (-12.4%, -20.5%) than with valsartan (-2.7%, -12.5%, P < 0.05 vs. both). RVR changes, adjusted for GFR changes, were associated with those in proteinuria (P < 0.05). Changes in glomerular permeability were comparable and did not predict different changes in proteinuria in the three groups.

Conclusion: At comparable blood pressure, combined ACEi and ARA decreased proteinuria better than ACEi and ARA. The greater antiproteinuric effect most likely depended on an ACEi-related hemodynamic effect, in addition to glomerular size selectivity amelioration. Long-term combined ACEi and ARA therapy may be more renoprotective than treatment with each agent alone.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Antihypertensive Agents / administration & dosage*
  • Benzazepines / administration & dosage*
  • Chronic Disease
  • Cross-Over Studies
  • Dextrans / pharmacokinetics
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate / drug effects
  • Glomerulonephritis, IGA / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Proteinuria / drug therapy*
  • Renal Circulation / drug effects
  • Tetrazoles / administration & dosage*
  • Valine / administration & dosage*
  • Valine / analogs & derivatives
  • Valsartan


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzazepines
  • Dextrans
  • Tetrazoles
  • Valsartan
  • Valine
  • benazepril