Cited by 466Chronic Kidney Disease and DiabetesHormonal Regulation and HypertensionRenin-Angiotensin System Studies

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Effectiveness of Aldosterone Blockade in Patients With Diabetic Nephropathy

Sato, Atsuhisa, Hayashi, Koichi, Naruse, Mitsuhide, Saruta, Takao·2003·Hypertension

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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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BackgroundInfluential
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“…risk of CV mortality (relative risk 0.34) and all-cause mortality relative to controls (relative risk 0.40), however quality of evidence deemed low Sato et al. (2003) DN Spironolactone Reduced LV mass index, without BP change Taheri et al. (2009) Haemodialysis in patients with moderate…”
BackgroundInfluential
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“This phenomenon may be attributed to the long-term administration of ACEIs and/or ARBs (14.5±4.8 months) leading to a failure to further significantly decrease the urine protein level.”
Influential
Long-term effect of efonidipine therapy on plasma aldosterone and left ventricular mass index in patients with essential hypertension
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Background
Increased glucocorticoid metabolism in diabetic kidney disease
Ackermann, D., Vogt, B., Bochud, M., Burnier, M., Martin, P., Paccaud, F. M., Ehret, G., Guessous, I., Ponte, B., Pruijm, M. T., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0269920 · Cited by 14
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BackgroundResult
Inhibition of the renal renin‐angiotensin system and renoprotection by pitavastatin in type 1 diabetes
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Background
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Background
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Background
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Self-citation
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New approaches to blockade of the renin-angiotensin-aldosterone system: mineralocorticoid-receptor blockers exert antihypertensive and renoprotective effects independently of the renin-angiotensin system.
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Self-citation
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BackgroundMethodInfluentialSelf-citation
Efficacy of low-dose spironolactone on top of angiotensin receptor blockade in patients with glomerulonephritis
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BackgroundResult
A serine protease inhibitor attenuates aldosterone-induced kidney injuries via the suppression of plasmin activity.
Kakizoe, Y., Miyasato, Y., Onoue, T., Nakagawa, T., Hayata, M., Uchimura, K., Morinaga, J., Mizumoto, T., Adachi, M., Miyoshi, T., et al. (2016) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2016.09.005 · Cited by 10
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BackgroundInfluential
Effects of Dual Blockade of the Renin Angiotensin System in Diabetic Kidney Disease: A Systematic Review and Meta-Analysis
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Background
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Background
Involvement of mineralocorticoid receptor in high glucose-induced big mitogen-activated protein kinase 1 activation and mesangial cell proliferation
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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
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2003-01
Volume: 41
Issue: 1
Pages: 64-68
ISSN: 0194-911X (ISSN-L)
1524-4563
DOI: 10.1161/01.hyp.0000044937.95080.e9
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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Effectiveness of Aldosterone Blockade in Patients With Diabetic Nephropathy

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