Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: a multicenter, randomized clinical trial

Sawako Kato, Shoichi Maruyama, Hirofumi Makino, Jun Wada, Daisuke Ogawa, Takashi Uzu, Hisazumi Araki, Daisuke Koya, Keizo Kanasaki, Yutaka Oiso, Motomitsu Goto, Akira Nishiyama, Hiroyuki Kobori, Enyu Imai, Masahiko Ando, Seiichi Matsuo

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44 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1098-1106
Number of pages9
JournalClinical and Experimental Nephrology
Issue number6
Publication statusPublished - Dec 1 2015


  • Albuminuria
  • Diabetic nephropathy
  • Randomized study
  • Spironolactone

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)


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