Sawako Kato1, Shoichi Maruyama2, Hirofumi Makino3, Jun Wada3, Daisuke Ogawa3, Takashi Uzu4, Hisazumi Araki4, Daisuke Koya5, Keizo Kanasaki5, Yutaka Oiso6, Motomitsu Goto6, Akira Nishiyama7, Hiroyuki Kobori7, Enyu Imai8, Masahiko Ando9, Seiichi Matsuo2. 1. Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan. kato07@med.nagoya-u.ac.jp. 2. Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan. 3. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 4. Department of Medicine, Shiga University of Medical Science, Shiga, Japan. 5. Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan. 6. Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Aichi, Japan. 7. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan. 8. Nakayama-temple Imai Clinic, Hyogo, Japan. 9. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Aichi, Japan.
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 eitherangiotensin-converting enzyme inhibitors or angiotensin receptor blockers. METHODS:Fifty-two Japanese patients with diabetic nephropathy and albuminuria (100 mg/gCr-2000 mg/gCr) treated withrenin-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.
RCT Entities:
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.
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