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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MRAs reduce albuminuria in people with diabetic nephropathy.
“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]
The Results section reports significantly reduced urinary albumin excretion after spironolactone was added to ACE-inhibitor treatment. The finding was in 13 patients with diabetic nephropathy and aldosterone escape, so it does not establish the unqualified claim for MRAs generally or for people with diabetic nephropathy outside that subgroup. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMRAs reduce albuminuria in people with diabetic nephropathy.
“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]
Mineralocorticoid receptor antagonists reduce albuminuria in people with diabetic nephropathy.
“In addition, mineralocorticoid receptor antagonists reduce albuminuria in people with diabetic nephropathy (82 -84).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [82]
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“Pilot studies in humans showed that addition of spironolactone to ACE inhibitors had no hemodynamic effects but markedly reduced proteinuria in patients with renal failure (4) and in patients with type 2 diabetes (39).”
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- 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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