Trial reportHypertension research : official journal of the Japanese Society of Hypertension2023
The renoprotective effect of esaxerenone independent of blood pressure lowering: a post hoc mediation analysis of the ESAX-DN trial.
Trial report in Hypertension research : official journal of the Japanese Society of Hypertension, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Cardiorenal Effects of Switching from Eplerenone to Esaxerenone in Patients with Chronic Heart Failure and Hypertension: A Prospective Clinical Study.Journal of personalized medicine · 2026Article
- Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy.Journal of pharmaceutical analysis · 2026Review
- Novel Therapeutic Strategies for Obesity-Related Glomerulopathy.Current hypertension reports · 2025Review
- A Prospective Crossover Clinical Trial of Esaxerenone and Eplerenone in Patients with Chronic Heart Failure Complicated by Hypertension.Life (Basel, Switzerland) · 2025Article
- Comparison of kidney and hepatic outcomes among sodium-glucose cotransporter-2 inhibitors: a retrospective study using multiple propensity scores.Journal of pharmaceutical health care and sciences · 2024Article
- Exploratory study on the relationship between urinary sodium/potassium ratio, salt intake, and the antihypertensive effect of esaxerenone: the ENaK Study.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- 2023 update and perspectives.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Rationale and design of a multicenter randomized study comparing the efficacy and safety of esaxerenone versus trichlormethiazide in patients with uncontrolled essential hypertension: EXCITE-HT study.Journal of clinical hypertension (Greenwich, Conn.) · 2023Article
- Esaxerenone for nocturnal hypertension and possible future direction for treatment of hypertension-cardiovascular-kidney comorbidity.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Nighttime home blood pressure lowering effect of esaxerenone in patients with uncontrolled nocturnal hypertension: the EARLY-NH study.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Mineralocorticoid Receptor Antagonists for Preventing Chronic Kidney Disease Progression: Current Evidence and Future Challenges.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are recommended as first-line drugs for hypertension with diabetic nephropathy owing to their renoprotective effect; however, their effect beyond lowering blood pressure (BP) has not been confirmed. Recent studies have shown that aldosterone plays a key role in causing renal injury; therefore, it is likely that mineralocorticoid receptor (MR) blockers inhibit aldosterone-induced renal damage in different ways from ACE inhibitors and ARBs. Therefore, we investigated the mechanism of the effect of an MR blocker on reducing the urinary albumin-to-creatinine ratio (UACR) using data from a randomized, double-blind, placebo-controlled phase 3 study (ESAX-DN) of a new nonsteroidal MR blocker, esaxerenone. This post hoc analysis used a novel statistical method to quantitatively estimate the effect of esaxerenone on UACR reduction mediated, or not mediated, by changes in systolic BP (SBP) and/or estimated glomerular filtration rate (eGFR). The proportion of the mediated effect by SBP changes to the total effect on UACR reduction was 9.8-10.7%; the UACR was reduced to 0.903-0.911 times the baseline at the end of treatment through the SBP-related pathway and to 0.422-0.426 times the baseline through the non-SBP-related pathway. Even considering both SBP and eGFR simultaneously, the proportion of the mediated effect was 21.9-28.1%. These results confirm that esaxerenone has a direct UACR-lowering effect independent of BP lowering and that its magnitude is much larger than that of the BP-dependent effect. Thus, esaxerenone could be a UACR-reducing treatment option for patients with diabetic nephropathy.
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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 Socratic graph.