Hypertension. 2003;41:64-68
Published online before print November 18, 2002, doi: 10.1161/01.HYP.0000044937.95080.E9
Published online before print November 18, 2002, doi: 10.1161/01.HYP.0000044937.95080.E9
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(Hypertension. 2003;41:64.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
Effectiveness of Aldosterone Blockade in Patients With Diabetic Nephropathy
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
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|
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|
|
|
|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S M Marshall Recent advances in diabetic nephropathy Postgrad. Med. J., November 1, 2004; 80(949): 624 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gross and F. Pistrosch Hyperkalaemia: again Nephrol. Dial. Transplant., September 1, 2004; 19(9): 2163 - 2166. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|