title: Comparison of the antialbuminuric effects of benidipine and hydrochlorothiazide in Renin-Angiotensin System (RAS) inhibitor-treated hypertensive patients with albuminuria: the COSMO-CKD (COmbination Strategy on Renal Function of Benidipine or Diuretics TreatMent with RAS inhibitOrs in a Chronic Kidney Disease Hypertensive Population) study.
abstract: OBJECTIVE
  This study evaluated the non-inferiority of renoprotection afforded by benidipine versus hydrochlorothiazide in hypertensive patients with chronic kidney disease (CKD).
  
  
  METHODS
  In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of benidipine and hydrochlorothiazide were examined in renin-angiotensin system (RAS) inhibitor-treated patients with blood pressure (BP) readings of ≥ 130/80 mmHg and ≤ 180/110 mmHg, a urinary albumin to creatinine ratio (UACR) of ≥ 300 mg/g, and an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73m(2). Patients received benidipine (n = 176, final dose: 4.8 mg/day) or hydrochlorothiazide (n = 170, 8.2 mg/day) for 12 months.
  
  
  RESULTS
  Benidipine and hydrochlorothiazide exerted similar BP- and eGFR-decreasing actions. The UACR values for benidipine and hydrochlorothiazide were 930.8 (95% confidence interval: 826.1, 1048.7) and 883.1 (781.7, 997.7) mg/g at baseline, respectively. These values were reduced to 790.0 (668.1, 934.2) and 448.5 (372.9, 539.4) mg/g at last observation carried forward (LOCF) visits. The non-inferiority of benidipine versus hydrochlorothiazide was not demonstrated (benidipine/hydrochlorothiazide ratio of LOCF value adjusted for baseline: 1.67 (1.40, 1.99)).
  
  
  CONCLUSIONS
  The present study failed to demonstrate the non-inferiority of the antialbuminuric effect of benidipine relative to that of hydrochlorothiazide in RAS inhibitor-treated hypertensive patients with macroalbuminuria.
authors.affiliation: 1. Division of Molecular Cardiovascular Metabolism, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ando
authors.affiliation: 2. Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
authors.affiliation: 3. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: 4. Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
authors.affiliation: 5. Division of Nephrology, Kanazawa Medical University School of Medicine, Ishikawa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: 6. Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: 7. Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara
authors.affiliation: 8. Department of Nephrology, Graduate School of Faculty of Life Science, Kumamoto University, Kumamoto, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
authors.affiliation: 9. Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
authors.affiliation: 9. Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: 9. Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Isshiki
authors.affiliation: 10. Department of Clinical Laboratory, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimosawa
authors.affiliation: 11. Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000139:chemically induced / Q000473:pathology; D017311:Amlodipine / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004095:Dihydropyridines / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D004095:Dihydropyridines; D006852:Hydrochlorothiazide; D017311:Amlodipine; C061004:benidipine
keywords: L-/N-/T-type calcium channel blocker, thiazide diuretic, urinary albumin.; chronic kidney disease, hypertension, renin-angiotensin system inhibitor