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Effectiveness of Aldosterone Blockade in Patients With Diabetic Nephropathy
Abstract
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.
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“In addition, MRAs reduce albuminuria in people with diabetic nephropathy (89)(90)(91).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [89]
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“In addition, MRAs reduce albuminuria in people with diabetic nephropathy (83–85).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [83]
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“In addition, mineralocorticoid receptor antagonists reduce albuminuria in people with diabetic nephropathy (82 -84).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [82]
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“Current recommendations for the treatment of hypertensive diabetics include the use of ACEi or ARB to block the renin-angiotensin system; however, in diabetics with proteinuria incompletely corrected with an ACEi, the addition of spironolactone has clear additive effects on decreasing protein excretion, with an additi…”
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“13 Aldosterone receptor blockade also provides beneficial effects in patients with diabetic nephropathy”
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“In their subsequent report, in patients with aldosterone breakthrough, the addition of spironolactone (25 mg/day) resulted in a 30% decrease in urinary albumin excretion (24).”
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“Excessive levels of aldosterone result in conditions as HF, hypertension and CKD [34-38], and inhibition of the activity of the renin-angiotensin-aldosterone system (RAAS) results in improved outcomes.”
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Metadata
- Authors
- Sato, A., Hayashi, K., Naruse, M., & Saruta, T.
- Affiliations
- Keio University (JP)
- 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.
- ORCID
- Naruse, Mitsuhide
- Venue
- Hypertension
- Published
- 2003-01
- Volume
- 41
- Issue
- 1
- Pages
- 64-68
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2163709605
- Cited by
- 466
- References
- 0
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 5 · 2023: 15 · 2022: 20 · 2021: 9 · 2020: 10 · 2019: 13 · 2018: 11 · 2017: 4 · 2016: 13 · 2015: 16 · 2014: 20 · 2013: 19 · 2012: 28
- FWCI
- 28.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- aldosterone escape, aldosterone blockade, spironolactone, ACE inhibitors, diabetic nephropathy, type 2 diabetes, urinary albumin excretion, proteinuria, left ventricular mass, renin-angiotensin system
- MeSH terms
- Albuminuria, Aldosterone, Mineralocorticoid Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Drug Therapy, Combination, Female, Heart Ventricles, Humans, Male, Middle Aged, Spironolactone, Ultrasonography
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