title: Urinary albumin excretion during angiotensin II receptor blockade: comparison of combination treatment with a diuretic or a calcium-channel blocker.
abstract: 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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi, Japan. yoshio@jichi.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Matsui
authors.forename: Kazuo
authors.initials: K
authors.lastname: Eguchi
authors.forename: Joji
authors.initials: J
authors.lastname: Ishikawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000188:drug therapy*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003404:Creatinine / Q000652:urine; D004095:Dihydropyridines / Q000627:therapeutic use*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004232:Diuretics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012890:Sleep; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; D007093:Imidazoles; D013777:Tetrazoles; C075750:8-epi-prostaglandin F2alpha; D001383:Azetidinecarboxylic Acid; C437965:olmesartan; D002097:C-Reactive Protein; D003404:Creatinine; D015237:Dinoprost; C061679:azelnidipine