Urinary albumin excretion during angiotensin II receptor blockade: comparison of combination treatment with a diuretic or a calcium-channel blocker.

BACKGROUND

We aimed to test the hypothesis that the angiotensin II receptor blocker (ARB)/diuretic combination decreases the urinary albumin/creatinine ratio (UACR) to a greater extent than treatment with the ARB/calcium-channel blocker (CCB) combination through a mechanism related to a greater reduction of sleep blood pressure (BP).

METHODS

We conducted a prospective, randomized, open-label, blinded end-point trial in hypertensive patients. Patients received olmesartan monotherapy for 12 weeks, followed by an additional use of hydrochlorothiazide (HCTZ) (n = 104) or azelnidipine (n = 103) for 24 weeks after randomization. The measurements of central and ambulatory BP, and laboratory tests were performed at baseline and the end of the study.

RESULTS

The adjusted percent reduction in UACR in the olmesartan/HCTZ group was significantly greater than that in the olmesartan/azelnidipine group (-43.2 vs. -24.0%, P = 0.0014), although the olmesartan/azelnidipine group showed greater decreases in central systolic BP (SBP; P = 0.04), oxidative stress (urinary 8-isoprostane; P = 0.02), inflammation (high-sensitivity C-reactive protein; P = 0.04), and insulin resistance (the homeostasis model assessment insulin resistance index (HOMA(IR)); P < 0.001) than the olmesartan/HCTZ group. In multivariate regression analyses, the significant determinants of change in UACR in the olmesartan/HCTZ group were changes in sleep SBP (P < 0.001), central SBP (P = 0.01), estimated glomerular filtration rate (eGFR) (P = 0.02), and HOMA(IR) (P = 0.03), and those in the olmesartan/azelnidipine group were changes in central SBP (P = 0.001) and urinary 8-isoprostane (P = 0.02).

CONCLUSIONS

These data showed that the ARB/diuretic combination decreased UACR significantly more than the ARB/CCB combination, and this decrease in UACR was associated with a greater magnitude reduction in sleep SBP.