Effects of Olmesartan and Azilsartan on Albuminuria and the Intrarenal Renin-Angiotensin System

Abstract

Pages 07-10 7 www.wjrr.org  Abstract-Purpose: Olmesartan and azilsartan decrease blood pressure more effectively than other angiotensin receptor blockers (ARBs). ARBs additionally decrease the urinary albumin to creatinine ratio (UACR), a urinary albumin marker, and urinary angiotensinogen (u-AGT), an intrarenal renin-angiotensin system activity marker. We examined the effects of these ARBs on blood pressure, UACR, and u-AGT in patients with uncontrolled hypertension.Methods: Patients with uncontrolled hypertension treated with conventional ARBs, excluding olmesartan and azilsartan, for over 8 weeks were enrolled. We randomly switched patients from their prior ARBs to either olmesartan or azilsartan, and followed them for 24 weeks.Results: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and central systolic blood pressure (cSBP) significantly decreased at 24 weeks. UACR and u-AGT also decreased at 24 weeks in both groups. There were no significant differences in SBP, DBP, cSBP, UACR, or u-AGT between the groups. Therefore, we combined both groups for further analyses. After combining, SBP (160.5 ± 16.4 to 139.6 ± 15.6 mm Hg, P < 0.0001), DBP (88.4 ± 13.7 to 80.7 ± 13.2 mm Hg, P = 0.008), cSBP (167.4 ± 20.8 to 146.6 ± 24.6 mm Hg, P < 0.0001), UACR (13.8 to 9.0 mg/g Cre, P = 0.0096), and u-AGT (4.13 to 2.32 µg/g Cre, P = 0.0074) significantly decreased at 24 weeks. Patients with microalbuminuria (UACR ≥ 30 mg/g Cre) had significantly greater ΔUACR (-39.4 vs 0.27, P = 0.0024) and Δu-AGT (-11.9 vs -0.61, P = 0.0235) than patients without microalbuminuria. The changes in u-AGT were significantly associated with changes in UACR (r = 0.411, P = 0.046); however, there was no significant relationship between the changes in u-AGT and those in SBP or DBP.Conclusion: Olmesartan and azilsartan decreased blood pressure, UACR, and u-AGT more than the other ARBs, and exerted depressor and renoprotective effects.Index Terms-blood pressure, urinary albumin, urinary angiotensinogen, angiotensin receptor blockers.

Stronger Effect of Azilsartan on Reduction of Proteinuria Compared to Candesartan in Patients with CKD: A Randomized Crossover Trial

“…Azilsartan (20 mg) significantly reduced blood pressure compared with candesartan in the current study. This result is consistent with that of previous studies of azilsartan and azilsartan medoxomil, a prodrug of azilsartan, which showed that the blood pressure-reducing effects of azilsartan and azilsartan medoxomil might be even stronger than those of other ARBs [20][21][22][28][29][30][31][32][33][34].…”

“…To the best of our knowledge, this is the first study of azilsartan in which the primary outcome is proteinuria. Furthermore, the level of proteinuria in the current study was higher than that in another study using azilsartan [18,[20][21][22][23][24]. We demonstrated that azilsartan had beneficial antiproteinuric and antihypertensive effects in patients with proteinuric CKD compared with candesartan, an older ARB.…”

“…The reno-protective effect of azilsartan has not been well assessed. Shiga et al [20] and Takami et al [21] demonstrated that azilsartan (20 mg) and olmesartan medoxomil (20 mg) decreased blood pressure equally, and both drugs decreased the urinary albumin-to-Cr ratio equally. Kakio et al [22] demonstrated that azilsartan (20 mg) and olmesartan medoxomil (20 mg) decreased blood pressure equally but only azilsartan significantly decreased urinary albumin.…”

“…ARBs demonstrate reno-protective effects, and these effects are partially mediated by direct effects on the kidney which are independent of antihypertensive effects [16]. Takami et al [21] demonstrated that the changes in urinary angiotensinogen, which is a biomarker of intrarenal RAS activation [26], were associated with the changes in the urinary albumin-to-Cr ratio; however, they were not associated with the changes in blood pressure. In a study in Zucker diabetic fatty rats, azilsartan decreased proteinuria compared with candesartan, although these drugs did not affect blood pressure [27].…”

Gastroprotective Effect of Azilsartan Through Ameliorating Oxidative Stress, Inflammation, and Restoring Hydroxyproline, and Gastrin Levels in Ethanol-Induced Gastric Ulcer

“… 35 Azilsartan also showed a superior effect in lowering blood pressure and protein urea compared to candesartan, 36 Furthermore, it has been proven for possessing a reno-protective effect. 37 , 38 All the aforementioned advantages of azilsartan encouraged us to test it in the ulcer model.…”