Bakris GL et al. (2008) Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study. Kidney Int 73: 1303–1309

Adding a calcium-channel blocker (CCB) or a diuretic to an angiotensin-converting enzyme inhibitor (ACEI) further reduces blood pressure in patients who have diabetes and hypertension; however, the impact on albuminuria is unknown.

The 52-week double-blind, randomized, controlled GUARD (Gauging Albuminuria Reduction with Lotrel in Diabetic Patients With Hypertension) trial enrolled 332 hypertensive patients with albuminuria and type 2 diabetes mellitus to test the hypothesis that the combination of the ACEI benazepril and the CCB amlodipine would produce comparable reductions in blood pressure and albuminuria to those elicited by the combination of benazepril and the diuretic hydrochlorothiazide.

Both combinations significantly reduced blood pressure and urinary albumin to creatinine ratio (P <0.0001 for all); however, the median reduction in urinary albumin to creatinine ratio achieved with the benazepril–diuretic combination was significantly greater than that obtained with the benazepril–CCB combination (−72.1% vs −40.5%; P <0.0001). Furthermore, the percentage of patients with microalbuminuria who attained a normal urinary albumin to creatinine ratio was higher with combined ACEI–diuretic therapy than with combined ACEI–CCB treatment (69.2% vs 47.8%; P = 0.0004). Conversely, the mean reduction in diastolic blood pressure was significantly greater in the ACEI–CCB group than in the ACEI–diuretic group (−13.1 mmHg vs −9.97 mmHg; P = 0.02). Both combinations were well tolerated.

The authors note that there was a greater decline in estimated glomerular filtration rate among the patients who received the diuretic rather than the CCB, which could account for the larger decrease in albuminuria in the diuretic group.