Donate Help Contact The AHA Sign In Home
American Heart Association
Hypertension
Search: search_blue_button Advanced Search
Hypertension. 2003;41:64-68
Published online before print November 18, 2002, doi: 10.1161/01.HYP.0000044937.95080.E9
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
41/1/64    most recent
01.HYP.0000044937.95080.E9v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sato, A.
Right arrow Articles by Saruta, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sato, A.
Right arrow Articles by Saruta, T.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Diabetes
*Diabetic Kidney Problems
Hazardous Substances DB
*SPIRONOLACTONE
Related Collections
Right arrow Clinical Studies

(Hypertension. 2003;41:64.)
© 2003 American Heart Association, Inc.


Scientific Contributions

Effectiveness of Aldosterone Blockade in Patients With Diabetic Nephropathy

Atsuhisa Sato; Koichi Hayashi; Mitsuhide Naruse; Takao Saruta

From the Department of Internal Medicine, Mito Red Cross Hospital (A.S.), Ibaraki; the Department of Internal Medicine, Keio University (K.H., T.S.), Tokyo; and the Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women’s Medical University (M.N.), Tokyo, Japan.

Correspondence to Atsuhisa Sato, MD, PhD, Department of Internal Medicine, Mito Red Cross Hospital, 3-12-48 San-nomaru, Mito city, Ibaraki, 310-0011, Japan. E-mail atsu-sa{at}pb3.so-net.ne.jp

It has been reported that continuous ACE inhibitor therapy does not necessarily produce a maintained decrease in plasma aldosterone levels, which may remain high or increase eventually during long-term use (aldosterone escape). We have examined the role of aldosterone escape in 45 patients with type 2 diabetes and early nephropathy treated with an ACE inhibitor for 40 weeks. With treatment, there was a 40% reduction in average urinary albumin excretion, although urinary albumin excretion in patients with aldosterone escape (18 patients) was significantly higher than that in patients without escape (27 patients). In the 18 patients with escape, spironolactone (25 mg/d) was added to ACE inhibitor treatment in 13. After a 24-week study period, urinary albumin excretion and left ventricular mass index were significantly reduced without blood pressure change. In conclusion, the present study demonstrates that aldosterone escape is observed in 40% of patients with type 2 diabetes with early nephropathy despite the use of ACE inhibitors. Our study suggests the possibility that aldosterone blockade may represent optimal therapy for patients with early diabetic nephropathy who show aldosterone escape during ACE inhibitor treatment and who no longer show maximal antiproteinuric effects of ACE inhibition. Additional, larger, prospectively randomized, double-blind studies will be needed before adaptation of this strategy.


Key Words: aldosterone • angiotensin-converting enzyme • diabetic nephropathy hemodialysis • hypertrophy • ventricular function, left




This article has been cited by other articles:


Home page
Nephrol Dial TransplantHome page
Y. S. Kang, G. J. Ko, M. H. Lee, H. K. Song, S. Y. Han, K. H. Han, H. K. Kim, J. Y. Han, and D. R. Cha
Effect of eplerenone, enalapril and their combination treatment on diabetic nephropathy in type II diabetic rats
Nephrol. Dial. Transplant., August 5, 2008; (2008) gfn448v1.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
N. Oyamada, M. Sone, K. Miyashita, K. Park, D. Taura, M. Inuzuka, T. Sonoyama, H. Tsujimoto, Y. Fukunaga, N. Tamura, et al.
The Role of Mineralocorticoid Receptor Expression in Brain Remodeling after Cerebral Ischemia
Endocrinology, August 1, 2008; 149(8): 3764 - 3777.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
K. Graf, T. Hucko, and P. Stawowy
Cardiac Benefits of Mineralocorticoid Receptor Inhibition in Renal Failure
Hypertension, August 1, 2008; 52(2): 209 - 210.
[Full Text] [PDF]


Home page
Exp PhysiolHome page
H. M. Siragy and C. Xue
Local renal aldosterone production induces inflammation and matrix formation in kidneys of diabetic rats
Exp Physiol, July 1, 2008; 93(7): 817 - 824.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
H. Otani, F. Otsuka, K. Inagaki, J. Suzuki, T. Miyoshi, Y. Kano, J. Goto, T. Ogura, and H. Makino
Aldosterone Breakthrough Caused by Chronic Blockage of Angiotensin II Type 1 Receptors in Human Adrenocortical Cells: Possible Involvement of Bone Morphogenetic Protein-6 Actions
Endocrinology, June 1, 2008; 149(6): 2816 - 2825.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
L. Vogt, F. Waanders, F. Boomsma, D. de Zeeuw, and G. Navis
Effects of Dietary Sodium and Hydrochlorothiazide on the Antiproteinuric Efficacy of Losartan
J. Am. Soc. Nephrol., May 1, 2008; 19(5): 999 - 1007.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
S. Gauer, V. Segitz, and M. Goppelt-Struebe
Aldosterone induces CTGF in mesangial cells by activation of the glucocorticoid receptor
Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3154 - 3159.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
H. V. Joffe, R. Y. Kwong, M. D. Gerhard-Herman, C. Rice, K. Feldman, and G. K. Adler
Beneficial Effects of Eplerenone Versus Hydrochlorothiazide on Coronary Circulatory Function in Patients with Diabetes Mellitus
J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2552 - 2558.
[Abstract] [Full Text] [PDF]


Home page
CJASNHome page
C. Catena, G. Colussi, E. Nadalini, A. Chiuch, S. Baroselli, R. Lapenna, and L. A. Sechi
Relationships of Plasma Renin Levels with Renal Function in Patients with Primary Aldosteronism
Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(4): 722 - 731.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
N. A. Bobadilla and G. Gamba
New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone
Am J Physiol Renal Physiol, July 1, 2007; 293(1): F2 - F9.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
K. Hayashi, S. Wakino, N. Sugano, Y. Ozawa, K. Homma, and T. Saruta
Ca2+ Channel Subtypes and Pharmacology in the Kidney
Circ. Res., February 16, 2007; 100(3): 342 - 353.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
L. C. Rump
Secondary rise of albuminuria under AT1-receptor blockade--what is the potential role of aldosterone escape?
Nephrol. Dial. Transplant., January 1, 2007; 22(1): 5 - 8.
[Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
J. Perez-Rojas, J. A. Blanco, C. Cruz, J. Trujillo, V. S. Vaidya, N. Uribe, J. V. Bonventre, G. Gamba, and N. A. Bobadilla
Mineralocorticoid receptor blockade confers renoprotection in preexisting chronic cyclosporine nephrotoxicity
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F131 - F139.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
M. Nagase, S. Yoshida, S. Shibata, T. Nagase, T. Gotoda, K. Ando, and T. Fujita
Enhanced Aldosterone Signaling in the Early Nephropathy of Rats with Metabolic Syndrome: Possible Contribution of Fat-Derived Factors
J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3438 - 3446.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
J. Lepenies and M. Quinkler
MR blockade in patients with chronic renal disease--not the more the merrier, but the earlier the better
Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3343 - 3344.
[Full Text] [PDF]


Home page
QJMHome page
N.C. Edwards, R.P. Steeds, C.J. Ferro, and J.N. Townend
The treatment of coronary artery disease in patients with chronic kidney disease
QJM, November 1, 2006; 99(11): 723 - 736.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
C. Guo, D. Martinez-Vasquez, G. P. Mendez, M. F. Toniolo, T. M. Yao, E. M. Oestreicher, T. Kikuchi, N. Lapointe, L. Pojoga, G. H. Williams, et al.
Mineralocorticoid Receptor Antagonist Reduces Renal Injury in Rodent Models of Types 1 and 2 Diabetes Mellitus
Endocrinology, November 1, 2006; 147(11): 5363 - 5373.
[Abstract] [Full Text] [PDF]


Home page
CJASNHome page
M. Epstein, G. H. Williams, M. Weinberger, A. Lewin, S. Krause, R. Mukherjee, R. Patni, and B. Beckerman
Selective Aldosterone Blockade with Eplerenone Reduces Albuminuria in Patients with Type 2 Diabetes
Clin. J. Am. Soc. Nephrol., September 1, 2006; 1(5): 940 - 951.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
G.-P. Sun, M. Kohno, P. Guo, Y. Nagai, K. Miyata, Y.-Y. Fan, S. Kimura, H. Kiyomoto, K. Ohmori, D.-T. Li, et al.
Involvements of Rho-Kinase and TGF-beta Pathways in Aldosterone-Induced Renal Injury
J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2193 - 2201.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
J.P. Habashi, D.P. Judge, T.M. Holm, R.D Cohn, B. Loeys, T.K. Cooper, L. Myers, E.C. Klein, G. Liu, C. Calvi, et al.
Losartan in Marfan Syndrome--Beyond Blood Pressure Lowering: Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome. Science 312: 117-121, 2006
J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1759 - 1764.
[Full Text] [PDF]


Home page
CJASNHome page
M. P. Ponda and T. H. Hostetter
Aldosterone Antagonism in Chronic Kidney Disease
Clin. J. Am. Soc. Nephrol., July 1, 2006; 1(4): 668 - 677.
[Full Text] [PDF]


Home page
JAMAHome page
L. A. Sechi, M. Novello, R. Lapenna, S. Baroselli, E. Nadalini, G. L. Colussi, and C. Catena
Long-term renal outcomes in patients with primary aldosteronism.
JAMA, June 14, 2006; 295(22): 2638 - 2645.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
S.-Y. Han, C.-H. Kim, H.-S. Kim, Y.-H. Jee, H.-K. Song, M.-H. Lee, K.-H. Han, H.-K. Kim, Y.-S. Kang, J.-Y. Han, et al.
Spironolactone Prevents Diabetic Nephropathy through an Anti-Inflammatory Mechanism in Type 2 Diabetic Rats
J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1362 - 1372.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
A. Covic, P. Gusbeth-Tatomir, and D. J. A. Goldsmith
Is it time for spironolactone therapy in dialysis patients?
Nephrol. Dial. Transplant., April 1, 2006; 21(4): 854 - 858.
[Full Text] [PDF]


Home page
CJASNHome page
R. E. Gilbert, K. Connelly, D. J. Kelly, C. A. Pollock, and H. Krum
Heart Failure and Nephropathy: Catastrophic and Interrelated Complications of Diabetes
Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 193 - 208.
[Abstract] [Full Text] [PDF]


Home page
CJASNHome page
A. Chrysostomou, E. Pedagogos, L. MacGregor, and G. J. Becker
Double-Blind, Placebo-Controlled Study on the Effect of the Aldosterone Receptor Antagonist Spironolactone in Patients Who Have Persistent Proteinuria and Are on Long-Term Angiotensin-Converting Enzyme Inhibitor Therapy, with or without an Angiotensin II Receptor Blocker
Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 256 - 262.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
K. Miyata, M. Rahman, T. Shokoji, Y. Nagai, G.-X. Zhang, G.-P. Sun, S. Kimura, T. Yukimura, H. Kiyomoto, M. Kohno, et al.
Aldosterone Stimulates Reactive Oxygen Species Production through Activation of NADPH Oxidase in Rat Mesangial Cells
J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2906 - 2912.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
Y. Nagai, K. Miyata, G.-P. Sun, M. Rahman, S. Kimura, A. Miyatake, H. Kiyomoto, M. Kohno, Y. Abe, M. Yoshizumi, et al.
Aldosterone Stimulates Collagen Gene Expression and Synthesis Via Activation of ERK1/2 in Rat Renal Fibroblasts
Hypertension, October 1, 2005; 46(4): 1039 - 1045.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
M. Quinkler, D. Zehnder, K. S. Eardley, J. Lepenies, A. J. Howie, S. V. Hughes, P. Cockwell, M. Hewison, and P. M. Stewart
Increased Expression of Mineralocorticoid Effector Mechanisms in Kidney Biopsies of Patients With Heavy Proteinuria
Circulation, September 6, 2005; 112(10): 1435 - 1443.
[Abstract] [Full Text] [PDF]


Home page
British Journal of Diabetes & Vascular DiseaseHome page
R. Kumar and P. H Winocour
Review: Dual blockade of the renin angiotensin system in diabetes -- rationale and risks
The British Journal of Diabetes & Vascular Disease, September 1, 2005; 5(5): 266 - 271.
[Abstract] [PDF]


Home page
Diabetes CareHome page
K. Rossing, K. J. Schjoedt, U. M. Smidt, F. Boomsma, and H.-H. Parving
Beneficial Effects of Adding Spironolactone to Recommended Antihypertensive Treatment in Diabetic Nephropathy: A randomized, double-masked, cross-over study
Diabetes Care, September 1, 2005; 28(9): 2106 - 2112.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
C. Xue and H. M. Siragy
Local Renal Aldosterone System and Its Regulation by Salt, Diabetes, and Angiotensin II Type 1 Receptor
Hypertension, September 1, 2005; 46(3): 584 - 590.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
M. Yoneda, H. Sanada, J. Yatabe, S. Midorikawa, S. Hashimoto, M. Sasaki, T. Katoh, T. Watanabe, P. M. Andrews, P. A. Jose, et al.
Differential Effects of Angiotensin II Type-1 Receptor Antisense Oligonucleotides on Renal Function in Spontaneously Hypertensive Rats
Hypertension, July 1, 2005; 46(1): 58 - 65.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
A. Fiebeler, J. Nussberger, E. Shagdarsuren, S. Rong, G. Hilfenhaus, N. Al-Saadi, R. Dechend, M. Wellner, S. Meiners, C. Maser-Gluth, et al.
Aldosterone Synthase Inhibitor Ameliorates Angiotensin II-Induced Organ Damage
Circulation, June 14, 2005; 111(23): 3087 - 3094.
[Abstract] [Full Text] [PDF]


Home page
Journal of Renin-Angiotensin-Aldosterone SystemHome page
P. K. Jacobsen
Review: Preventing End-Stage Renal Disease in Diabetic Patients -- Dual Blockade of the Renin-Angiotensin System (Part II)
Journal of Renin-Angiotensin-Aldosterone System, June 1, 2005; 6(2): 55 - 68.
[Abstract] [PDF]


Home page
HypertensionHome page
A. Nishiyama, L. Yao, Y. Fan, M. Kyaw, N. Kataoka, K. Hashimoto, Y. Nagai, E. Nakamura, M. Yoshizumi, T. Shokoji, et al.
Involvement of Aldosterone and Mineralocorticoid Receptors in Rat Mesangial Cell Proliferation and Deformability
Hypertension, April 1, 2005; 45(4): 710 - 716.
[Abstract] [Full Text] [PDF]


Home page
Diabetes CareHome page
J. L. Gross, M. J. de Azevedo, S. P. Silveiro, L. H. Canani, M. L. Caramori, and T. Zelmanovitz
Diabetic Nephropathy: Diagnosis, Prevention, and Treatment
Diabetes Care, January 1, 2005; 28(1): 164 - 176.
[Abstract] [Full Text] [PDF]


Home page
Postgrad. Med. J.Home page
S M Marshall
Recent advances in diabetic nephropathy
Postgrad. Med. J., November 1, 2004; 80(949): 624 - 633.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
P. Gross and F. Pistrosch
Hyperkalaemia: again
Nephrol. Dial. Transplant., September 1, 2004; 19(9): 2163 - 2166.
[Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
G. Deferrari, M. Ravera, V. Berruti, G. Leoncini, and L. Deferrari
Optimizing Therapy in the Diabetic Patient with Renal Disease: Antihypertensive Treatment
J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S6 - 11.
[Abstract] [Full Text]


Home page
J. Am. Soc. Nephrol.Home page
W. A. Wilmer, B. H. Rovin, C. J. Hebert, S. V. Rao, K. Kumor, and L. A. Hebert
Management of Glomerular Proteinuria: A Commentary
J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3217 - 3232.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
K. Yonemura, H. Yasuda, and A. Hishida
Distinct Responses of Membranoproliferative Glomerulonephritis-Related Proteinuria to Spironolactone with and without Angiotensin II Blockade
Ann Intern Med, November 4, 2003; 139(9): W-79 - W-79.
[Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
M. Epstein
Aldosterone receptor blockade and the role of eplerenone: evolving perspectives
Nephrol. Dial. Transplant., October 1, 2003; 18(10): 1984 - 1992.
[Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
T. H. Hostetter and H. N. Ibrahim
Aldosterone in Chronic Kidney and Cardiac Disease
J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2395 - 2401.
[Abstract] [Full Text] [PDF]