ArticleAmerican journal of translational research2016
An additive effect of eplerenone to ACE inhibitor on slowing the progression of diabetic nephropathy in the db/db mice.
Article in American journal of translational research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Eplerenone Attenuates Hepatic Oxidative Stress and Mitochondrial Dysfunction Following Renal Ischemia-Reperfusion Injury in Rats.Advanced pharmaceutical bulletin · 2026Article
- Effects of perirenal fat accumulation on cardiometabolic and renal functions and mineralocorticoid receptor activation in primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease.International journal of molecular sciences · 2024Review
- Cardiorenal diseases in type 2 diabetes mellitus: clinical trials and real-world practice.Nature reviews. Endocrinology · 2023Review
- Mineralocorticoid receptor antagonists in diabetic kidney disease - mechanistic and therapeutic effects.Nature reviews. Nephrology · 2022Review
- Mineralocorticoid Receptor Antagonism Prevents the Synergistic Effect of Metabolic Challenge and Chronic Kidney Disease on Renal Fibrosis and Inflammation in Mice.Frontiers in physiology · 2022Article
- Therapeutic mechanism and clinical application of Chinese herbal medicine against diabetic kidney disease.Frontiers in pharmacology · 2022Review
- Immunomodulatory Potential of Diuretics.Biology · 2021Review
- Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2021Article
- Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Regulation of Monocytes/Macrophages by the Renin-Angiotensin System in Diabetic Nephropathy: State of the Art and Results of a Pilot Study.International journal of molecular sciences · 2021Review
- Nuclear receptors in podocyte biology and glomerular disease.Nature reviews. Nephrology · 2021Review
- Synergistic reduction in albuminuria in type 2 diabetic mice by esaxerenone (CS-3150), a novel nonsteroidal selective mineralocorticoid receptor blocker, combined with an angiotensin II receptor blocker.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Article
- Systemic AAV10.COMP-Ang1 rescues renal glomeruli and pancreatic islets in type 2 diabetic mice.BMJ open diabetes research & care · 2020Article
- miR-196b-5p-enriched extracellular vesicles from tubular epithelial cells mediated aldosterone-induced renal fibrosis in mice with diabetes.BMJ open diabetes research & care · 2020Article
- Advanced Glycation End Products: Potential Mechanism and Therapeutic Target in Cardiovascular Complications under Diabetes.Oxidative medicine and cellular longevity · 2019Review
- Mineralocorticoid receptor blockade for renoprotection.Kidney research and clinical practice · 2018Article
- Article
- Mineralocorticoid Receptor Signaling as a Therapeutic Target for Renal and Cardiac Fibrosis.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Although blockade of the renin-angiotensin-system (RAS) has become standard therapy for diabetic nephropathy (DN), decline in kidney function towards end-stage renal disease is seen in many patients. Elevated plasma aldosterone often accompanies RAS blockade by a phenomenon known as "aldosterone escape" and activates the mineralocorticoid receptor (MR). We therefore examined whether addition of the MR antagonist eplerenone to an ACEI would enhance the efficacy in slowing the progression of DN. Untreated uninephrectomized diabetic db/db mice developed progressive albuminuria and glomerulosclerosis between weeks 18 and 22, associated with decreased number of podocytes and increased renal expression of fibrotic markers. The therapeutic effect of eplerenone at 100 mg/kg BW/d on albuminuria, podocyte injury and renal fibrosis was similar to that of enalapril given alone at maximally effective doses. Adding eplerenone to enalapril resulted in further reduction in these measurements. Renal expressions of TNF-α, MCP-1, Nox2 and p47phox and renal TBARS levels, markers of inflammation and oxidative stress, were increased during disease progression in diabetic mice, which were reduced by eplerenone or enalapril given alone and further reduced by the two drugs given in combination. However, there were no treatment related effects on plasma K+. Our results suggest that eplerenone is effective in slowing the progression of DN in db/db mice and that the effect is additive to an ACEI. The addition of an MR antagonist void of effects on plasma K+ to an ACEI may offer additional renoprotection in progressive DN via blocking the effects of aldosterone due to escape or diabetes-induction.
Indexed as
Identifiers
27186263PMC4859623W2413096040What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.