title: Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: a multicenter, randomized clinical trial.
abstract: BACKGROUND
  Several studies have demonstrated that spironolactone has an anti-albuminuric property in diabetic nephropathy. As an adverse event, spironolactone often induces the elevation of creatinine levels with hypotension and hyperkalemia. Therefore, we aimed to evaluate the efficacy and safety of spironolactone in Japanese patients with type 2 diabetes treated with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
  
  
  METHODS
  Fifty-two Japanese patients with diabetic nephropathy and albuminuria (100 mg/gCr-2000 mg/gCr) treated with renin-angiotensin system (RAS) blockade were enrolled in a prospective, randomized, open-label study. The patients were subjected to add-on treatment with spironolactone 25 mg once daily and compared with matched controls for 8 weeks. The primary outcome was a reduction in the rate of albuminuria at 8 weeks compared with the baseline value. This study was registered with UMIN Clinical Trials Registry (000008016).
  
  
  RESULTS
  Albuminuria was reduced by 33 % (95 % confidence interval: 22-54; P = 0.0002) at 8 weeks with spironolactone. In the spironolactone group, blood pressure tended to lower and the estimated glomerular filtration rate (eGFR) was significantly decreased compared to those in the control group. When adjusted by systolic blood pressure and eGFR, spironolactone treatment still showed a significant effect on albuminuria reduction in a linear mixed model (coefficient ± standard error; 514.4 ± 137.6 mg/gCr, P < 0.0005). No patient was excluded from the study because of hyperkalemia.
  
  
  CONCLUSIONS
  Spironolactone reduced albuminuria along with conventional RAS inhibitors in patients with diabetic nephropathy. Our study suggests that spironolactone exerts anti-albuminuric effects independent of systemic hemodynamic alterations.
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan. kato07@med.nagoya-u.ac.jp.
authors: Sawako
authors: S
authors: Kato
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors: Shoichi
authors: S
authors: Maruyama
authors: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Hirofumi
authors: H
authors: Makino
authors: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Jun
authors: J
authors: Wada
authors: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Daisuke
authors: D
authors: Ogawa
authors: Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
authors: Takashi
authors: T
authors: Uzu
authors: Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
authors: Hisazumi
authors: H
authors: Araki
authors: Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan.
authors: Daisuke
authors: D
authors: Koya
authors: Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan.
authors: Keizo
authors: K
authors: Kanasaki
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors: Yutaka
authors: Y
authors: Oiso
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors: Motomitsu
authors: M
authors: Goto
authors: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors: Akira
authors: A
authors: Nishiyama
authors: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors: Hiroyuki
authors: H
authors: Kobori
authors: Nakayama-temple Imai Clinic, Hyogo, Japan.
authors: Enyu
authors: E
authors: Imai
authors: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Aichi, Japan.
authors: Masahiko
authors: M
authors: Ando
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors: Seiichi
authors: S
authors: Matsuo
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy*; D000450:Aldosterone / Q000097:blood; D044466:Asian People; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone
keywords: Albuminuria; Diabetic nephropathy; Randomized study; Spironolactone