Minnebro (esaxerenone) / Daiichi Sankyo, Exelixis - LARVOL DELTA

Aldosterone-Induced Renal Lymphangiogenesis and Endothelial-To-Mesenchymal Transformation to Promote Renal Interstitial Fibrosis Through the MR/TGF-β1 Pathway in Mice. (PubMed, Front Biosci (Landmark Ed)) - "Aldosterone induces inflammatory injury, thereby promoting renal lymphangiogenesis and EndMT."

Journal • Preclinical • Fibrosis • Immunology • CD68 • FLT4 • IL1B • LYVE1 • PDPN • TGFB1 • TNFA • VEGFC • VIM

A novel mineralocorticoid receptor blocker, CS-3150, improves insulin resistance and reduces inflammation in db/db mice. (PubMed, Korean J Physiol Pharmacol) - "CS-3150 treatment reversed this effect, whereas the traditional MR antagonist eplerenone failed to do so at equivalent concentrations. In conclusion, CS-3150 improved insulin sensitivity in obese diabetic mice, likely through attenuation of adipose inflammation, reduction in fat accumulation, and enhancement of insulin signaling. These findings support the potential of CS-3150 as a therapeutic agent for obesity-associated metabolic dysfunction."

Journal • Preclinical • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • IL6 • VCAM1

Evidence-based validation of cardiovascular benefits from novel MRAs in type 2 diabetes: A meta-analysis of over 30,000 patients. (PubMed, J Diabetes Complications) - "This study provides high-certainty evidence supporting MRAs in reducing MACE and heart failure hospitalization, and moderate-certainty evidence for benefits on cardiovascular mortality. Cardioprotective effects may involve Ras, IL-17, and relaxin signaling."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus • EGFR • IL17A • MAPK10 • MMP1 • NOS2 • PACERR • PTGS2

Regulation of Klotho Production by Mineralocorticoid Receptor Signaling in Renal Cell Lines. (PubMed, Biomolecules) - "Using four renal cell lines, Madin-Darby canine kidney (MDCK), normal rat kidney, subtype 52E (NRK-52E), human kidney 2 (HK2) cells, and primary renal proximal tubule epithelial cells (RPTECs), and the four most frequently prescribed mineralocorticoid receptor blockers, spironolactone, eplerenone, finerenone, and esaxerenone, we assessed Klotho gene expression by qRT-PCR and Klotho protein by Western blotting. To conclude, common mineralocorticoid receptor antagonists are characterized by highly diverse effects on Klotho in four renal cell lines. Further studies are needed to define the role of mineralocorticoid receptor blockade for Klotho production."

Journal • Preclinical • Endocrine Disorders • Fibrosis • Heart Failure • Immunology • Inflammation • Nephrology • Renal Disease • KL

Molecular and Structural Changes in Bone Under Aldosterone-Salt Hypertension Uncovered by Transcriptome-Wide Profiling (KIDNEY WEEK 2025) - "These changes were associated with disrupted bone matrix gene regulation and were effectively prevented by mineralocorticoid receptor blockade. Our findings highlight a novel bone–kidney axis and support esaxerenone as a potential therapeutic agent for aldosterone-salt–induced osteopathy."

Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Hypertension • Osteoporosis • Renal Disease • COL1A1 • COL5A1 • FGF23

Esaxerenone Ameliorates Glomerular Hyperfiltration in Diabetic Kidney Disease by Restoring Tubuloglomerular Feedback via Macula Densa MR Blockade (KIDNEY WEEK 2025) - "Funding Commercial Support – DAIICHI SANKYO COMPANY Background The FIDELIO-DKD trial demonstrated that finerenone, a non-steroidal selective mineralocorticoid receptor blocker (MRB), suppresses kidney failure and disease progression in diabetic kidney disease (DKD). In MD cells, MR activation increased NO production and reduced membrane expression of the Na + -K + -2Cl - cotransporter (NKCC2). Conclusion MR activation in macula densa cells contributes to glomerular hyperfiltration via a TGF-mediated mechanism in DKD."

Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • NGFR

The Nonsteroidal Mineralocorticoid Receptor Blocker Esaxerenone reduces glomerular hyperfiltration and albuminuria. (PubMed, Nephrol Dial Transplant) - "These findings suggest that esaxerenone restores TGF function via adenosine signaling, attenuating glomerular hyperfiltration and reducing albuminuria. This study provides novel insights into the albuminuria-lowering effects of MR blockade in DKD and supports the therapeutic potential of esaxerenone."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • NGFR

Effect of N-terminal pro B-type natriuretic peptide levels on the efficacy and safety of esaxerenone vs trichlormethiazide for the treatment of Japanese patients with uncontrolled essential hypertension: a subanalysis of the EXCITE-HT study. (PubMed, Hypertens Res) - "No cases of serum potassium level ≥6.0 mEq/L were reported. These findings suggest that esaxerenone is efficacious across a wide range of baseline NT-proBNP levels, while also supporting its favorable safety profile."

Journal • Cardiovascular • Hypertension

Esaxerenone Attenuates High Salt-Induced Hypertension and Renal Damage via CD8+T Cell- Associated NCC Activation in Aldosterone Treated Rats. (PubMed, J Steroid Biochem Mol Biol) - "In conclusion, aldosterone plus high salt diet enhances renal infiltration of CD8+T cells and upregulates NCC expression and phosphorylation, resulting in hypertension and kidney injury. Esaxerenone antagonizes the activation of mineralocorticoid receptors to decrease the infiltration of CD8+T cells and the phosphorylation level of NCC, thereby alleviating salt-water retention and kidney injury."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease • CD8

Real-world use of finerenone in diabetic kidney disease: eGFR slope analysis with exploratory data on prior MRA use. (PubMed, Diabetol Int) - "Notably, one-third of patients had switched from other MRAs, most commonly esaxerenone. These findings highlight the favorable renal effects of finerenone, even in high-risk patients previously managed with other MRAs. Finerenone may offer incremental benefit for eGFR preservation and supports its role in comprehensive DKD management."

Journal • Real-world evidence • Cardiovascular • Diabetic Nephropathy • Nephrology • Renal Disease

Esaxerenone inhibits renal macrophage proliferation through MR/TGF-β1 pathway in db/db mice. (PubMed, Life Sci) - "Esaxerenone inhibits renal macrophage proliferation mediated by high glucose-induced activation of MR and downstream TGF-β1 signaling pathways, thereby mitigating inflammatory and fibrotic damage. These findings suggest that MR blockade may directly target macrophage proliferation and inflammation in DKD."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Fibrosis • Inflammation • Nephrology • Renal Disease • MRC1 • TGFB1

Effect of Esaxerenone in Patients With Persistent Atrial Fibrillation and Hypertension After Catheter Ablation. (PubMed, Cureus) - "Conclusions Esaxerenone did not suppress the recurrence of AF in our cohort of patients with persistent AF and hypertension after catheter ablation. However, we suggest that esaxerenone is cardioprotective by reducing brain natriuretic peptide levels and LVMI."

Journal • Atrial Fibrillation • Cardiovascular • Hypertension • NPPB

Clinical Outcomes In Patients With Heart Failure Managed With Non-steroidal Vs Steroidal Mineralocorticoid Receptor Antagonists: A Propensity-score Matched Analysis. (HFSA 2025) - "We aim to assess the outcomes associated with Non-Steroidal versus Steroidal in Heart Failure patients. We queried the TriNetx Global Collaborative Network for all adults diagnosed with Heart Failure (HF) between 01/01/2020 to 12/31/2023 and created two cohorts: first cohort started on Non-Steroidal MRAs-Finerenone and Esaxerenone after HF diagnosis and the second cohort started on Steroidal MRAs-Spironolactone and Eplerenone. In our study, the use of nonsteroidal MRAs in comparison to steroidal MRAs in individuals with HF was associated with a reduction in the risk for all-cause mortality, MACCE, acute heart failure, acute pulmonary edema, respiratory failure, hyperkalemia, hypotension. Further research and more data like head-to-head clinical trials are needed to establish a clear advantage of nonsteroidal MRAs over steroidal MRAs."

Clinical • Clinical data • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Diabetic Nephropathy • Genetic Disorders • Heart Failure • Hypertension • Hypotension • Ischemic stroke • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Respiratory Diseases • Vascular Neurology

Rationale and Design of the ESPIAL Trial　- A Prospective, Randomized, Exploratory Study to Evaluate the Effect of Esaxerenone on Reduction of Urinary Albumin to Creatinine Ratio in Hypertensive Patients Concomitant With Heart Failure and Albuminuria. (PubMed, Circ Rep) - "The primary outcome was the ratio of UACR before treatment and 24 weeks after treatment. The ESPIAL trial evaluates the effect of esaxerenone on reduction of UACR in hypertensive patients concomitant with HF and albuminuria."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Hypertension • Renal Disease

Esaxerenone Attenuates Atherogenesis and Vascular Dysfunction in Apolipoprotein E-Deficient Mice. (PubMed, Int Heart J) - "In an ex vivo vascular reactivity assay using ApoE-/- aortic rings, esaxerenone diminished aldosterone-induced endothelial dysfunction. In an in vitro experiment, aldosterone decreased the phosphorylation of eNOSSer1177 and increased the phosphorylation of eNOSThr495 in a dose-dependent manner, which were attenuated by esaxerenone in HUVECs.Esaxerenone ameliorated hyperlipidemia-induced atherosclerotic plaque progression and vascular dysfunction in ApoE-/- mice, suggesting that esaxerenone is a promising therapeutic approach for cardiovascular complications."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation • APOE • ICAM1 • TERC

Blocking of mineralocorticoid signalling reduces atherosclerosis in hyperglycaemia-induced ApoE knockout mice without altering glycolipid metabolism (EASD 2025) - "Blocking of mineralocorticoid signaling by esaxerenone exerts anti-atherosclerotic effects through the direct modulation of inflammatory pathways in vascular smooth muscle cells, without impacting blood pressure or glycolipid metabolism. The reduction in plaque formation in the aortic arch is likely driven by the attenuation of oxidative stress and inflammation-related signaling pathways. These findings suggest that MR blockade with esaxerenone may represent a promising therapeutic strategy for atherosclerosis, particularly in the context of diabetes, through its molecular action on vascular smooth muscle cells and inflammatory mechanisms."

Preclinical • Diabetes • Metabolic Disorders • APOE • ICAM1 • IL1B • IL6 • VCAM1

Efficacy and safety of esaxerenone with and without sodium-glucose cotransporter-2 inhibitor use in hypertensive patients with type 2 diabetes mellitus: a pooled analysis of five clinical studies. (PubMed, Hypertens Res) - "Esaxerenone demonstrated significant BP-lowering effects, and improved renal and cardiovascular parameters, regardless of SGLT2i use. Safety was consistent across groups, with the numerically lower incidence of serum potassium ≥5.5 mEq/L in the SGLT2i subgroup suggesting a potential mitigating effect of SGLT2is on the risk of hyperkalemia."

Journal • Retrospective data • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Esaxerenone for Essential Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, J Clin Med) - " In patients with essential HTN, esaxerenone was shown to be safe and well-tolerated compared with usual care. Long-term data on safety is warranted."

Journal • Retrospective data • Review • Cardiovascular • Hypertension

Expanding the therapeutic frontier: esaxerenone in hypertensive patients with CKD and albuminuria. (PubMed, Hypertens Res) - No abstract available

Journal • Chronic Kidney Disease • Renal Disease

Safety of esaxerenone (CS-3150) and its impacts on blood pressure and renal function: A systematic review and meta-analysis. (PubMed, Medicine (Baltimore)) - "ESAX appears reasonably safe, with a modest risk of hyperkalemia and worsening of renal function, and modest efficacy in the treatment of hypertension and albuminuria."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Hypertension • Renal Disease

Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies. (PubMed, Hypertens Res) - "This study showed that esaxerenone significantly lowered morning home, bedtime home, and office BP and UACR in hypertensive patients with CKD, regardless of T2DM status and kidney function (eGFR), and without any novel safety concerns. These highlight the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Diabetes • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Esaxerenone improves the blood pressure and metabolic parameters of hypertensive subjects with diabetes. (PubMed, Endocr J) - "Esaxerenone has an antihypertensive effect, reduces the albuminuria, and reduces the activities of liver enzymes in hypertensive subjects with type 2 diabetes/prediabetes. The present findings suggest that esaxerenone has pleiotropic effects in such subjects."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

A Prospective Crossover Clinical Trial of Esaxerenone and Eplerenone in Patients with Chronic Heart Failure Complicated by Hypertension. (PubMed, Life (Basel)) - "This effect, together with its strong antihypertensive effect and reduced urinary albumin-to-creatinine ratio, suggests that esaxerenone improves kidney function. The results of this small-scale, single-center study need to be expanded to a larger-scale investigation, but esaxerenone shows promise as a treatment for chronic heart failure with hypertension."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

Aldosterone induces renal lymphangiogenesis through macrophage-lymphatic endothelial cell transformation and Inhibition by esaxerenone. (PubMed, Inflamm Res) - "Our data suggest that renal fibrosis occurs in aldosterone-treated rats and that inflammation-induced macrophage transdifferentiation into LECs occurs during this process and that MRB attenuates renal fibrosis and lymphangiogenesis due to inflammatory injury."

Journal • Fibrosis • Immunology • Inflammation • Renal Disease • VEGFC

Chronic esaxerenone treatment improves vascular function and lowers peripheral arterial stiffness in patients with idiopathic hyperaldosteronism. (PubMed, J Hypertens) - "Esaxerenone improved vascular function and peripheral arterial stiffness in patients with IHA. These findings suggest aldosterone inhibition is a potential mechanism governing improvement in cardiovascular health."

Journal • Cardiovascular • Endocrine Disorders • Hypertension