Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study

Kidney Int. 2008 Jun;73(11):1303-9. doi: 10.1038/ki.2008.102. Epub 2008 Mar 19.


Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Albuminuria / drug therapy*
  • Albuminuria / etiology
  • Amlodipine / adverse effects
  • Amlodipine / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use
  • Benzazepines / adverse effects
  • Benzazepines / pharmacology
  • Benzazepines / therapeutic use*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diuretics / adverse effects
  • Diuretics / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydrochlorothiazide / adverse effects
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / drug therapy
  • Hypertension / etiology
  • Male
  • Middle Aged
  • Treatment Outcome


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzazepines
  • Calcium Channel Blockers
  • Diuretics
  • Hydrochlorothiazide
  • Amlodipine
  • benazepril