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Randomized Controlled Trial
. 2015 Dec;19(6):1098-106.
doi: 10.1007/s10157-015-1106-2. Epub 2015 Mar 21.

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

Sawako Kato  1 , Shoichi Maruyama  2 , Hirofumi Makino  3 , Jun Wada  3 , Daisuke Ogawa  3 , Takashi Uzu  4 , Hisazumi Araki  4 , Daisuke Koya  5 , Keizo Kanasaki  5 , Yutaka Oiso  6 , Motomitsu Goto  6 , Akira Nishiyama  7 , Hiroyuki Kobori  7 , Enyu Imai  8 , Masahiko Ando  9 , Seiichi Matsuo  2
Affiliations
Randomized Controlled Trial

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

Sawako Kato et al. Clin Exp Nephrol. 2015 Dec.

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.

Keywords: Albuminuria; Diabetic nephropathy; Randomized study; Spironolactone.

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Conflict of interest statement

Conflict of interest This study was funded by Nagoya University Graduate School of Medicine. This study was supported in part by a Grant-in-Aid for Progressive Renal Diseases Research, Research on Rare and Intractable Disease, from the Ministry of Health, Labour and Welfare of Japan. The Department of Nephrology, Nagoya University Graduate School of Medicine, reported receiving research promotion grants from Astellas, Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, Mochida, MSD, Nihon Medi-Physics, Novartis, Otsuka, Pfizer, Takeda, Teijin, Mitsubishi Tanabe and Torii. S.K. receives speaker honoraria from Novartis. Sh.M. receives speaker honoraria from Bayer, Chugai, Dainippon Sumitomo, Genzyme, Kowa, Kyowa Hakko Kirin, Mochida, MSD, Novartis, Otsuka, Public Health Research Center, Teijin and Mitsubishi Tanabe. Se.M. receives speaker honoraria from Alexon, Astellas, Baxter, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Kaneka Medix, Kyowa Hakko Kirin, Mochida, MSD, Nihon Medi-Physics, Novartis, Otsuka, Public Health Research Center, Sanwa, Takeda, Teijin, Mitsubishi Tanabe and Torii. However, the research topics of these donation grants are not restricted. The Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences receives grant support from Astellas, Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, MSD, Novo Nordisk, Pfizer, Takeda and Tanabe Mitsubishi. D.O. belongs to the Department of Diabetic Nephropathy, endowed by Boehringer Ingelheim, and receives grant support from Eli Lilly. J.W. is a consultant for Boehringer Ingelheim and receives speaker honoraria from Boehringer Ingelheim, Novartis and Novo Nordisk. H.M. is a consultant for AbbVie, Astellas and Teijin, and receives speaker honoraria from Astellas, MSD, Takeda and Tanabe Mitsubishi. However, the research topics of these donation grants are not restricted. Kanazawa Medical University receives donation from Pfizer and the donation is not directly associated with this study. Also, Kanazawa Medical University receives donation for research promotion from the following: MSD, Astellas, Kyowa Hakko Kirin, Daiichi Sankyo, Takeda, Mitsubishi Tanabe, Boehringer Ingelheim, Novartis and Japan Tobacco Inc. D.K. receives speaker honoraria from MSD, Astellas, Kyowa Hakko Kirin, Daiichi Sankyo, Takeda, Mitsubishi Tanabe, Boehringer Ingelheim, Novartis, Dainippon Sumitomo, Novo Nodisk, Sanofi, Kowa, Eli Lilly and Pfizer. K.K. receives speaker honoraria from, MSD, Astellas, Kyowa Hakko Kirin, Daiichi Sankyo, Mitsubishi Tanabe, Boehringer Ingelheim, Novartis, Dainippon Sumitomo, Sanofi and Eli Lilly. The Department of Medicine, Shiga University of Medical Science, reported receiving research promotion grants from Astellas, Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, MSD, Novartis, Pfizer, Takeda, Teijin, Mitsubishi Tanabe and Chugai. T.U. receives speaker honoraria from MSD. The Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, reported receiving research promotion grants from Astellas, Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, MSD, Kowa, Sanwa, Teijin, Mitsubishi Tanabe, Lilly and Novo Nordisk. Y.O. receives speaker honoraria from MSD and Ono. M.G. receives speaker honoraria from Astellas, Kowa, Mitsubishi Tanabe, Novo Nordisk, Takeda and Mochida. However, the research topics of these donation grants are not restricted. Department of Pharmacology, Faculty of Medicine, Kagawa University receives donation from Pfizer and the donation is not directly associated with this study. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, receives donation from Pfizer and the donation is not directly associated with this study. Pfizer organized the advisory meeting about aldosterone antagonist use in patients with diabetic nephropathy and S.K., Sh.M., H.M., T.U., K.K., E.I. and Se.M. were reimbursed for travel costs and received honoraria.

Figures

Fig. 1
Fig. 1
Line plot showing mean urinary albumin-to-creatinine ratio (a), mean serum creatinine (b) and mean estimated glomerular filtration rate (c). The squares represent the control group (Group C) and the circles represent the spironolactone group (Group S)
See this image and copyright information in PMC

References

    1. International Diabetes Federation. IDF Diabetes Altas. 6. Brussels: 2013. pp. 29–49.
    1. Nathan DM, Bayless M, Cleary P, Genuth S, Gubitosi-Klug R, Lachin JM, et al. Diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: advances and contributions. Diabetes. 2013;62(12):3976–86. doi: 10.2337/db13-1093. - DOI - PMC - PubMed
    1. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414(6865):782–7. doi: 10.1038/414782a. - DOI - PubMed
    1. Iseki K. Predictors of diabetic end-stage renal disease in Japan. Nephrol Carlton. 2005;10(Suppl):S2–6. doi: 10.1111/j.1440-1797.2005.00447.x. - DOI - PubMed
    1. Nakai S, Iseki K, Itami N, Ogata S, Kazama JJ, Kimata N, et al. Overview of regular dialysis treatment in Japan (as of 31 December 2009) Ther Apher Dial. 2012;16(1):11–53. doi: 10.1111/j.1744-9987.2011.01050.x. - DOI - PubMed

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