Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy

Kidney Int. 2003 May;63(5):1874-80. doi: 10.1046/j.1523-1755.2003.00940.x.

Abstract

Background: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. We tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) is superior to maximal recommended dose of ACE inhibitor in type 1 diabetic patients with diabetic nephropathy (DN).

Methods: We performed a randomized, double-blind, crossover trial with 8 weeks treatment with placebo and irbesartan 300 mg (once daily), added on top of enalapril 40 mg (once daily). We included 24 type 1 patients with DN. At the end of each treatment period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were measured.

Results: Values on ACE inhibitors + placebo were: albuminuria [mean (95% CI)], 519 (342 to 789) mg/24 hours; blood pressure [mean (SEM)], 131 (3)/74 (1) mm Hg, and GFR [mean (SEM)], 65 (5) mL/min/1.73 m2. Dual blockade of the RAS induced a reduction in albuminuria [mean (95% CI)] of 25% (15, 34) (P < 0.001), a reduction in systolic blood pressure of 8 mm Hg (4, 12) (P = 0.002), and a reduction of 4 mm Hg (2, 7) (P = 0.003) in diastolic blood pressure. GFR and plasma potassium remained unchanged during both treatment regimes. Dual blockade was safe and well tolerated.

Conclusion: Dual blockade of the RAS is superior to maximal recommended dose of ACE inhibitors with regard to lowering of albuminuria and blood pressure in type 1 patients with DN. Long-term trials are needed to further establish the role of dual blockade of the RAS in renal and cardiovascular protection.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / drug therapy
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Biphenyl Compounds / administration & dosage*
  • Biphenyl Compounds / adverse effects
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / complications
  • Diabetic Nephropathies / drug therapy*
  • Double-Blind Method
  • Drug Synergism
  • Drug Therapy, Combination
  • Enalapril / administration & dosage*
  • Enalapril / adverse effects
  • Female
  • Humans
  • Irbesartan
  • Male
  • Middle Aged
  • Renin-Angiotensin System / drug effects
  • Tetrazoles / administration & dosage*
  • Tetrazoles / adverse effects

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Tetrazoles
  • Enalapril
  • Irbesartan