Overactivation of mineralocorticoid receptors occurs in cardiorenal diseases. Many patients with type 2 diabetes often progress to chronic kidney disease (CKD) and require dialysis. Finerenone is the first oral non-steroidal mineralocorticoid receptor (MR) antagonist used in patients with diabetic kidney disease and heart failure. Finerenone (also known as Kerendia) is more potent than spironolactone in reducing the progression of CKD and exerts its effect equally on the heart and kidneys, improving cardiovascular outcomes. Research demonstrates that finerenone improves proteinuria and glomerular filtration rate (GFR) if taken alone or in combination with sodium-glucose transporter 2 inhibitors (SGLT2i). Finerenone has been found to decrease mortality in patients with diabetic renal disease and improve quality of life. Its side effects, unlike those of spironolactone, do not include gynecomastia. However, it can result in hyperkalemia, which needs to be monitored. In this narrative review, we aim to investigate the mechanisms of action of finerenone and its implications in patients with type 2 diabetes.

More than 90% of patients developing heart failure (HF) have an epidemiological background of hypertension. The most frequent concomitant conditions are type 2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease, all disorders/diseases closely related to hypertension.
HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and nonsteroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors.
For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). However, subsequently, they have been investigated and, as we see it, documented as beneficial in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) and mostly hypertensive etiology, with effect estimates assessed partly on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications.
Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated.

Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) show high rates of cardiorenal outcomes. In addition, the progression towards renal failure and cardiovascular events rises as CKD worsens. Several studies suggest that the activation of the mineralocorticoid receptor (MR) induces cardiac and renal injury, including inflammation and fibrosis. Finerenone is a novel, nonsteroidal, selective MR antagonist (MRA) which has demonstrated anti-inflammatory and anti-fibrotic effects in pre-clinical studies. Moreover, two large trials (FIDELIO-DKD and FIGARO-DKD) investigated the renal and cardiovascular outcomes in patients with mild to severe CKD in type 2 diabetes which received finerenone. On these bases, this comprehensive review aims to summarize the current knowledge regarding finerenone and its effects on CKD and the cardiovascular system, emphasizing its role in modifying cardiorenal outcomes.

In this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists (MRAs) have been found to concentration-dependently inhibit steroidogenesis in different degrees. However, many studies have proven the suppressive effects of MRAs on the activities of hormone synthase. The probable factors of cytochrome P-450 reduction, both in microsomes and mitochondria, have also been considered: (1) one of the spironolactone metabolite forms had destructive function, except canrenone, (2) 7α-thio-spironolactone was an obligatory intermediate in the spironolactone-induced CYP450 decrease, and (3) the contributing steroids should have 7α-methylthio or 7α-methylsulfone groups. In previous clinical research, spironolactone-body-containing cells showed a type II pattern of enzyme activity (i.e., enhanced 3β-hydroxysteroid dehydrogenase, glucose-6-phosphate, and NADP-isocitrate dehydrogenase activities and weaken succinate dehydrogenase activity), and the subcapsular micronodules composed of spironolactone-body-containing cells also exhibited a type II pattern and excess aldosterone secretion, indicating that the subcapsular micronodules might be the root of aldosterone-producing adenoma. Moreover, combined with the potential impeditive function to aldosterone secretion, a few cases of spontaneous remission of primary aldosteronism, with normal ranges of blood pressure, plasma potassium, plasma renin activity, and aldosterone renin ratio, have been reported after long-term treatment with MRAs.

OBJECTIVE: Both sodium-glucose cotransporter-2 (SGLT-2) inhibitors and mineralocorticoid receptor antagonists (MRAs) have been shown to reduce cardiovascular (CV) event in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). However, little evidence pertains to the benefits of their combined use.
METHODS: We systematically searched the PubMed, MEDLINE, EMBASE, and Cochrane Library databases through July 2022. We selected randomized controlled trials comparing SGLT-2 inhibitors, MRAs, or SGLT-2 inhibitor + MRA combination therapy, with placebo in patients with T2D and CKD. We performed a network meta-analysis to indirectly compare the treatments. The primary outcome was a composite of CV events.
RESULTS: Eight studies were selected with 36,186 patients. The primary outcome was significantly improved in the combination therapy group compared with the other groups (RR [95% CI]; vs SGLT-2 inhibitors, 0.76 [0.60; 0.96]; vs MRAs, 0.66 [0.53; 0.82]; vs placebo, 0.58 [0.47; 0.73]). Additionally, the combination therapy was associated with a considerable reduction in the risk of hyperkalemia (RR vs MRA, 0.43 [0.23; 0.79]).
CONCLUSIONS: Combination of SGLT-2 inhibitors and MRAs potentially reduced CV events compared with SGLT-2 inhibitors or MRAs alone. This combination may be a candidate treatment strategy for patients with T2D and CKD.

OBJECTIVE: Finerenone is a novel non-steroidal mineralocorticoid antagonist (MRA) recently approved for the treatment of chronic kidney disease (CKD) in people with type 2 diabetes (T2D). We aim to conduct a systematic review of finerenone to know the efficacy and safety of finerenone in CKD with or without T2D.
METHODS: A systematic search in the electronic database of PubMed and Google Scholar was made from inception until September 09, 2022, using several MeSH keywords related to finerenone. Ongoing trials were additionally searched from ClinicalTrials.Gov.
RESULTS: Five phase 2 and three phase 3, randomized, double-blind, placebo- or active-controlled studies of finerenone have been published to date and several other randomized and real-world studies of finerenone are currently undergoing.
CONCLUSIONS: In short-term studies in patients with CKD and reduced ejection heart failure, with or without T2D, finerenone 20 mg appears to have a better renal outcome compared with spironolactone and a better mortality outcome compared with eplerenone, with significantly lesser hyperkalemia compared to both spironolactone and finerenone. In long-term studies in patients with CKD and T2D, finerenone 10/20 mg significantly reduces the progression of renal disease and reduced CV endpoints (especially heart failure hospitalization) compared to placebo. Finerenone has no effect on HbA1c, body weight, and sexual side effects including gynecomastia, and has only a modest effect on blood pressure. However, hyperkalemia leading to drug withdrawal was significantly higher with finerenone compared to placebo. Safety data in real-world settings is a pressing priority.

Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been proposed. The protective effects of mineralocorticoid receptor antagonists (MRA) against tissue fibrosis, pulmonary and systemic vasoconstriction, and inflammation have been implicated in potentially attenuating the severity of SARS-CoV-2 infection by inhibiting the deleterious effects of aldosterone. Furthermore, spironolactone, a type of MRA, has been suggested to have a beneficial effect on SARS-CoV-2 outcomes through its dual action as an MRA and antiandrogen, resulting in reduced transmembrane protease receptor serine type 2 (TMPRSS2)-related viral entry to host cells. In this study, we sought to investigate the association between MRA antagonist therapy and mortality in SARS-CoV-2 patients via systematic review and meta-analysis. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE databases were searched for studies that reported the incidence of mortality in patients on MRA with SARS-CoV-2 infection. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using the random-effects model. Five studies with a total of 1,388,178 subjects (80,903 subjects receiving MRA therapy) met the inclusion criteria. We included studies with all types of MRA therapy including spironolactone and canrenone and found no association between MRA therapy and mortality in SARS-CoV-2 infection (OR = 0.387, 95% CI: 0.134-1.117, p = 0.079).

Based on global estimates, almost 10% of adults have diabetes, of whom 40% are estimated to also have chronic kidney disease (CKD). Almost 2 decades ago, treatments targeting the renin-angiotensin system (RAS) were shown to slow the progression of kidney disease. More recently, studies have reported the additive benefits of antihyperglycaemic sodium-glucose co-transporter-2 inhibitors in combination with RAS inhibitors on both CKD progression and cardiovascular outcomes. However, these recent data also showed that patients continue to progress to kidney failure or die from kidney- or cardiovascular-related causes. Therefore, new agents are needed to address this continuing risk. Overactivation of the mineralocorticoid (MR) receptor contributes to kidney inflammation and fibrosis, suggesting that it is an appropriate treatment target in patients with diabetes and CKD. Novel, selective non-steroidal MR antagonists are being studied in these patients, and the results of two large recently completed clinical trials have shown that one such treatment, finerenone, significantly reduces CKD progression and cardiovascular events compared with standard of care. This review summarizes the pathogenic mechanisms of CKD in type 2 diabetes and examines the potential benefit of novel disease-modifying agents that target inflammatory and fibrotic factors in these patients.

Primary aldosteronism (PA) is a common cause of secondary hypertension and associated with higher incidence of new-onset atrial fibrillation (NOAF). However, the effects of surgical or medical therapies on preventing NOAF in PA patents remain unclear. The aim of this meta-analysis study was to assess the risk of NOAF among PA patients receiving mineralocorticoid receptor antagonist (MRA) treatment, PA patients receiving adrenalectomy, and patients with essential hypertension.
We performed the meta-analysis of the randomized or observational studies that investigated the incidence rate of NOAF in PA patients receiving MRA treatment versus PA patients receiving adrenalectomy from database inception until December 01, 2020 which were identified from PubMed, Embase, and Cochrane Library.
A total of 172 related studies were reviewed, of which three fulfilled the inclusion criteria, including a total of 2,705 PA patients. The results of meta-analysis demonstrated a higher incidence of NOAF among the PA patients receiving MRA treatment compared to the PA patients receiving adrenalectomy (pooled odds ratio [OR]: 2.83, 95% confidence interval [CI]: 1.76-4.57 in the random effects model, I2 = 0%). The pooled OR for the PA patients receiving MRA treatment compared to the patients with essential hypertension was 1.91 (95% CI: 1.11-3.28). The pooled OR for the PA patients receiving adrenalectomy compared to the patients with essential hypertension was 0.70 (95% CI: 0.28-1.79).
Compared to the essential hypertension patients and the PA patients receiving adrenalectomy, the patients with PA receiving MRA treatment had a higher risk of NOAF.
https://www.crd.york.ac.uk/prospero/, identifier CRD42021222022.

There is an increasing number of therapeutic agents being developed for the treatment of pulmonary artery hypertension (PAH) which is a condition characterized by raised pulmonary artery pressure and right heart failure. Despite our better understanding of the pathophysiology of PAH, the treatment outcomes are still suboptimal. There is growing evidence suggesting the role of increases in the levels of aldosterone, which is a mineralocorticoid hormone, in the pathophysiology of PAH; however, the extent to which hyperaldosteronism is associated with PAH in patients is unclear. There are also a few studies assessing the effects of mineralocorticoid receptor antagonists (MRA) in PAH. MRAs are a recognized treatment for heart failure and hypertension. In this review, we focus on the relationship between aldosterone level in patients with PAH and right ventricular failure and the effect of MRAs on the PAH severity.