title: Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial.
abstract: BACKGROUND
  In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity.
  
  
  METHODS
  We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to <30 mg/g of albumin-to-creatinine ratio) or microalbuminuria (30 to <300 mg/g) to the DRI group or ARB group (any ARB) with a target blood pressure of <130/80 mmHg. The primary endpoint was a reduction in albuminuria.
  
  
  RESULTS
  Twelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients.
  
  
  CONCLUSIONS
  DRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen.
authors.affiliation: Division of Nephrology & Blood Purification, Nissay Hospital, Osaka, Japan.|Department of Medicine, Sihiga Univ. of Medical Science, Otsu, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.affiliation: Department of Medicine, Sihiga Univ. of Medical Science, Otsu, Shiga, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Araki
authors.affiliation: Department of Medicine, Kusatsu General Hospital, Kusatsu, Shiga, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.affiliation: Department of Medicine, Asahikawa Medical Univ., Asahikawa, Hokkaido, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
authors.affiliation: Department of Diabetology and Endocrinology, Kanazawa Medical Univ., Kahoku-gun, Ishikawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
authors.affiliation: Department of Internal Medicine, Jiyugaoka Medical Clinic, Obihiro, Hokkaido, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Department of Medicine, Daini-Okamoto Hospital, Uji, Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kida
authors.affiliation: Department of Internal Medicine, Ikebuchi Clonic, Osaka, Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Ikebuchi
authors.affiliation: Department of Endicrinology and Metabolism, Omi Hachiman Community Medical Center, Omi Hachiman, Shiga, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Medicine, Nagahama City Hospital, Nagahama, Shiga, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Medicine, Ako City Hospital, Ako, Hyogo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takahara
authors.affiliation: Department of Medicine, Ako City Hospital, Ako, Hyogo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Obata
authors.affiliation: Department of Medicine, Omichi Clinic, Otsu, Shiga, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Omichi
authors.affiliation: Department of Medicine, Sakamoto Clinic, Minoh, Osaka, Iapan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Medicine, Kitahorie Hospital, Osaka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Shingu
authors.affiliation: Diabetes Center, National Hospital Organization National Osaka Hospital, Osaka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Taki
authors.affiliation: Division of Metabolism and Endocrinology, St. Marianna Univ School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Medicine, Tokuda Clinic, Kitamatsu-ura-gun, Nagasaki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Department of Diabetology and Endocrinology, Kanazawa Medical Univ., Kahoku-gun, Ishikawa, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Kitada
authors.affiliation: Department of Medicine, Nagahama Red Cross Hospital, Nagahama, Shiga, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Misawa
authors.affiliation: Department of Pharmacology, Kagawa Univ. Kida-gun, Kagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Department of Pharmacology, Kagawa Univ. Kida-gun, Kagawa, Japan.|Graduate School of Health Science, Kokusai Iryo Fukushi Daigaku, Ohtawara, Tochigi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.affiliation: Department of Medicine, Sihiga Univ. of Medical Science, Otsu, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
mesh_terms: D000419:Albuminuria / Q000188:drug therapy*; D000577:Amides / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000808:Angiotensinogen / Q000652:urine; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000473:pathology; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000517:prevention & control*; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D057911:Angiotensin Receptor Antagonists; D000808:Angiotensinogen; D000959:Antihypertensive Agents; D003404:Creatinine; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren