Skip to main content
Erschienen in: Clinical and Experimental Nephrology 6/2015

01.12.2015 | Original Article

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

verfasst von: 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

Erschienen in: Clinical and Experimental Nephrology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat International Diabetes Federation (2013) IDF Diabetes Altas, 6 ed. Brussels. pp 29–49. International Diabetes Federation (2013) IDF Diabetes Altas, 6 ed. Brussels. pp 29–49.
2.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
6.
Zurück zum Zitat Makino H, Haneda M, Babazono T, Moriya T, Ito S, Iwamoto Y, et al. Microalbuminuria reduction with telmisartan in normotensive and hypertensive Japanese patients with type 2 diabetes: a post hoc analysis of The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) study. Hypertens Res. 2008;31(4):657–64. doi:10.1291/hypres.31.657.CrossRefPubMed Makino H, Haneda M, Babazono T, Moriya T, Ito S, Iwamoto Y, et al. Microalbuminuria reduction with telmisartan in normotensive and hypertensive Japanese patients with type 2 diabetes: a post hoc analysis of The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) study. Hypertens Res. 2008;31(4):657–64. doi:10.​1291/​hypres.​31.​657.CrossRefPubMed
7.
Zurück zum Zitat Araki S, Haneda M, Koya D, Hidaka H, Sugimoto T, Isono M, et al. Reduction in microalbuminuria as an integrated indicator for renal and cardiovascular risk reduction in patients with type 2 diabetes. Diabetes. 2007;56(6):1727–30. doi:10.2337/db06-1646.CrossRefPubMed Araki S, Haneda M, Koya D, Hidaka H, Sugimoto T, Isono M, et al. Reduction in microalbuminuria as an integrated indicator for renal and cardiovascular risk reduction in patients with type 2 diabetes. Diabetes. 2007;56(6):1727–30. doi:10.​2337/​db06-1646.CrossRefPubMed
10.
Zurück zum Zitat Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870–8. doi:10.1056/NEJMoa011489.CrossRefPubMed Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870–8. doi:10.​1056/​NEJMoa011489.CrossRefPubMed
11.
Zurück zum Zitat Makino H, Haneda M, Babazono T, Moriya T, Ito S, Iwamoto Y, et al. Prevention of transition from incipient to overt nephropathy with telmisartan in patients with type 2 diabetes. Diabetes Care. 2007;30(6):1577–8. doi:10.2337/dc06-1998.CrossRefPubMed Makino H, Haneda M, Babazono T, Moriya T, Ito S, Iwamoto Y, et al. Prevention of transition from incipient to overt nephropathy with telmisartan in patients with type 2 diabetes. Diabetes Care. 2007;30(6):1577–8. doi:10.​2337/​dc06-1998.CrossRefPubMed
13.
15.
Zurück zum Zitat Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care. 2005;28(9):2106–12.CrossRefPubMed Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care. 2005;28(9):2106–12.CrossRefPubMed
16.
Zurück zum Zitat Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70(12):2116–23. doi:10.1038/sj.ki.5001854.PubMed Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70(12):2116–23. doi:10.​1038/​sj.​ki.​5001854.PubMed
17.
Zurück zum Zitat Furumatsu Y, Nagasawa Y, Tomida K, Mikami S, Kaneko T, Okada N, et al. Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker. Hypertens Res. 2008;31(1):59–67. doi:10.1291/hypres.31.59.CrossRefPubMed Furumatsu Y, Nagasawa Y, Tomida K, Mikami S, Kaneko T, Okada N, et al. Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker. Hypertens Res. 2008;31(1):59–67. doi:10.​1291/​hypres.​31.​59.CrossRefPubMed
21.
23.
24.
Zurück zum Zitat Morales E, Millet VG, Rojas-Rivera J, Huerta A, Gutierrez E, Gutierrez-Solis E, et al. Renoprotective effects of mineralocorticoid receptor blockers in patients with proteinuric kidney diseases. Nephrol Dial Transplant. 2013;28(2):405–12. doi:10.1093/ndt/gfs429.CrossRefPubMed Morales E, Millet VG, Rojas-Rivera J, Huerta A, Gutierrez E, Gutierrez-Solis E, et al. Renoprotective effects of mineralocorticoid receptor blockers in patients with proteinuric kidney diseases. Nephrol Dial Transplant. 2013;28(2):405–12. doi:10.​1093/​ndt/​gfs429.CrossRefPubMed
25.
Zurück zum Zitat Esteghamati A, Noshad S, Jarrah S, Mousavizadeh M, Khoee SH, Nakhjavani M. Long-term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: a randomized clinical trial. Nephrol Dial Transplant. 2013;28(11):2823–33. doi:10.1093/ndt/gft281.CrossRefPubMed Esteghamati A, Noshad S, Jarrah S, Mousavizadeh M, Khoee SH, Nakhjavani M. Long-term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: a randomized clinical trial. Nephrol Dial Transplant. 2013;28(11):2823–33. doi:10.​1093/​ndt/​gft281.CrossRefPubMed
27.
Zurück zum Zitat Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709–17. doi:10.1056/NEJM199909023411001.CrossRefPubMed Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709–17. doi:10.​1056/​NEJM199909023411​001.CrossRefPubMed
28.
Zurück zum Zitat Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41(1):64–8.CrossRefPubMed Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41(1):64–8.CrossRefPubMed
30.
Zurück zum Zitat Shibata S, Nagase M, Yoshida S, Kawarazaki W, Kurihara H, Tanaka H, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nature medicine. 2008;14(12):1370–6. doi:10.1038/nm.1879.CrossRefPubMed Shibata S, Nagase M, Yoshida S, Kawarazaki W, Kurihara H, Tanaka H, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nature medicine. 2008;14(12):1370–6. doi:10.​1038/​nm.​1879.CrossRefPubMed
31.
Zurück zum Zitat Nishiyama A, Kobori H, Konishi Y, Morikawa T, Maeda I, Okumura M, et al. Mineralocorticoid receptor blockade enhances the antiproteinuric effect of an angiotensin II blocker through inhibiting podocyte injury in type 2 diabetic rats. The Journal of pharmacology and experimental therapeutics. 2010;332(3):1072–80. doi:10.1124/jpet.109.158113.PubMedCentralCrossRefPubMed Nishiyama A, Kobori H, Konishi Y, Morikawa T, Maeda I, Okumura M, et al. Mineralocorticoid receptor blockade enhances the antiproteinuric effect of an angiotensin II blocker through inhibiting podocyte injury in type 2 diabetic rats. The Journal of pharmacology and experimental therapeutics. 2010;332(3):1072–80. doi:10.​1124/​jpet.​109.​158113.PubMedCentralCrossRefPubMed
32.
Zurück zum Zitat Chen H, Sun F, Zhong X, Shao Y, Yoshimura A, Liu Y. Eplerenone-mediated aldosterone blockade prevents renal fibrosis by reducing renal inflammation, interstitial cell proliferation and oxidative stress. Kidney Blood Press Res. 2013;37(6):557–66. doi:10.1159/000355736.CrossRefPubMed Chen H, Sun F, Zhong X, Shao Y, Yoshimura A, Liu Y. Eplerenone-mediated aldosterone blockade prevents renal fibrosis by reducing renal inflammation, interstitial cell proliferation and oxidative stress. Kidney Blood Press Res. 2013;37(6):557–66. doi:10.​1159/​000355736.CrossRefPubMed
33.
Zurück zum Zitat Ojeda-Cervantes M, Barrera-Chimal J, Alberu J, Perez-Villalva R, Morales-Buenrostro LE, Bobadilla NA. Mineralocorticoid receptor blockade reduced oxidative stress in renal transplant recipients: a double-blind, randomized pilot study. Am J Nephrol. 2013;37(5):481–90. doi:10.1159/000350539.CrossRefPubMed Ojeda-Cervantes M, Barrera-Chimal J, Alberu J, Perez-Villalva R, Morales-Buenrostro LE, Bobadilla NA. Mineralocorticoid receptor blockade reduced oxidative stress in renal transplant recipients: a double-blind, randomized pilot study. Am J Nephrol. 2013;37(5):481–90. doi:10.​1159/​000350539.CrossRefPubMed
34.
Zurück zum Zitat Ziyadeh FN, Goldfarb S. The renal tubulointerstitium in diabetes mellitus. Kidney Int. 1991;39(3):464–75.CrossRefPubMed Ziyadeh FN, Goldfarb S. The renal tubulointerstitium in diabetes mellitus. Kidney Int. 1991;39(3):464–75.CrossRefPubMed
36.
Zurück zum Zitat Kramer AB, van der Meulen EF, Hamming I, van Goor H, Navis G. Effect of combining ACE inhibition with aldosterone blockade on proteinuria and renal damage in experimental nephrosis. Kidney Int. 2007;71(5):417–24. doi:10.1038/sj.ki.5002075.CrossRefPubMed Kramer AB, van der Meulen EF, Hamming I, van Goor H, Navis G. Effect of combining ACE inhibition with aldosterone blockade on proteinuria and renal damage in experimental nephrosis. Kidney Int. 2007;71(5):417–24. doi:10.​1038/​sj.​ki.​5002075.CrossRefPubMed
37.
Zurück zum Zitat Mavrakanas TA, Gariani K, Martin PY. Mineralocorticoid receptor blockade in addition to angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment: an emerging paradigm in diabetic nephropathy: a systematic review. Eur J Int Med. 2014;25(2):173–6. doi:10.1016/j.ejim.2013.11.007.CrossRef Mavrakanas TA, Gariani K, Martin PY. Mineralocorticoid receptor blockade in addition to angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment: an emerging paradigm in diabetic nephropathy: a systematic review. Eur J Int Med. 2014;25(2):173–6. doi:10.​1016/​j.​ejim.​2013.​11.​007.CrossRef
Metadaten
Titel
Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: a multicenter, randomized clinical trial
verfasst von
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
Publikationsdatum
01.12.2015
Verlag
Springer Japan
Erschienen in
Clinical and Experimental Nephrology / Ausgabe 6/2015
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-015-1106-2

Weitere Artikel der Ausgabe 6/2015

Clinical and Experimental Nephrology 6/2015 Zur Ausgabe

Acknowledgment

List of referees

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Vorhofflimmern bei Jüngeren gefährlicher als gedacht

06.05.2024 Vorhofflimmern Nachrichten

Immer mehr jüngere Menschen leiden unter Vorhofflimmern. Betroffene unter 65 Jahren haben viele Risikofaktoren und ein signifikant erhöhtes Sterberisiko verglichen mit Gleichaltrigen ohne die Erkrankung.

Chronisches Koronarsyndrom: Gefahr von Hospitalisierung wegen Herzinsuffizienz

06.05.2024 Herzinsuffizienz Nachrichten

Obwohl ein rezidivierender Herzinfarkt bei chronischem Koronarsyndrom wahrscheinlich die Hauptsorge sowohl der Patienten als auch der Ärzte ist, sind andere Ereignisse womöglich gefährlicher. Laut einer französischen Studie stellt eine Hospitalisation wegen Herzinsuffizienz eine größere Gefahr dar.

„Restriktion auf vier Wochen Therapie bei Schlaflosigkeit ist absurd!“

06.05.2024 Insomnie Nachrichten

Chronische Insomnie als eigenständiges Krankheitsbild ernst nehmen und adäquat nach dem aktuellen Forschungsstand behandeln: Das forderte der Schlafmediziner Dr. Dieter Kunz von der Berliner Charité beim Praxis Update.

GLP-1-Rezeptoragonisten und SGLT-2-Hemmer: zusammen besser

06.05.2024 Typ-2-Diabetes Nachrichten

Immer häufiger wird ein Typ-2-Diabetes sowohl mit einem GLP-1-Rezeptor-Agonisten als auch mit einem SGLT-2-Inhibitor behandelt. Wie sich das verglichen mit den Einzeltherapien auf kardiovaskuläre und renale Komplikationen auswirkt, wurde anhand von Praxisdaten aus Großbritannien untersucht.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.