Diuretics are widely used antihypertensive agents because of their potent natriuretic effects. However, in hypertension with excessive renin-angiotensin-aldosterone system (RAAS) activation, further volume depletion may aggravate target-organ injury. We investigated the effects of loop diuretics and mineralocorticoid receptor (MR) blockade on plasma volume (PV) and organ injury in angiotensin II (Ang II)-induced hypertension. Male Sprague-Dawley rats were assigned to six groups (n = 6/group) receiving Sham or Ang II with or without furosemide and spironolactone. PV was measured by indocyanine green (ICG) dilution, together with blood pressure, histological, immunohistochemical, and molecular assessments. Longitudinal data were analyzed by two-way repeated-measures ANOVA; animal-level endpoints by one-way ANOVA; histological and immunohistochemical measurements by nested one-way ANOVA; and two-group comparisons by unpaired t tests, with appropriate post hoc testing. Ang II reduced PV, whereas furosemide caused a further decline without additional blood pressure reduction, accompanied by aggravated fibrosis, endothelial impairment, and dysregulation of fibrosis-related proteins. Spironolactone attenuated PV contraction, lowered blood pressure, preserved endothelial integrity, alleviated fibrosis, and partially normalized molecular alterations. MR blockade was associated with attenuation of PV contraction and target-organ injury, supporting a potential relationship between PV homeostasis and organ protection during chronic loop diuretic treatment.

Mineralocorticoid receptor antagonists (MRAs) are a well-established treatment option for the management of heart failure (HF) with reduced ejection fraction. However, high-quality evidence for the effect of MRAs in the treatment of heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) has been limited until recent years. The nonsteroidal MRA finerenone has demonstrated efficacy in this population and was approved for treatment in July 2025 by the U.S. Food and Drug Administration. A call to action is needed to increase the use of guideline-directed medical therapy in HFmrEF/HFpEF with simultaneous or rapid sequence initiation of a combination therapy. This review provides an overview of MRAs approved for use in HF management, with particular focus on HFmrEF/HFpEF. Guideline recommendations and HF label indications are discussed, highlighting practical considerations for the safe use of MRAs in clinical practice. In addition, the therapeutic management of patients with HFmrEF/HFpEF and concomitant cardiovascular, kidney, and metabolic diseases is considered.

Atrial arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) remains common despite advances in pulmonary vein isolation, mapping, lesion delivery, and rhythm monitoring. Contemporary guidelines emphasize integrated, risk-factor-based care, yet the roles of serum potassium management and mineralocorticoid receptor antagonist (MRA) therapy after ablation remain poorly defined. We aimed to synthesize the clinical and mechanistic evidence on whether serum potassium, potassium-management strategies, and MRA therapy (steroidal: spironolactone, eplerenone; nonsteroidal: esaxerenone, finerenone) modify recurrence, and to derive a testable mechanistic framework. Considering these backgrounds, we conducted a narrative review supported by a systematic literature search, prepared with reference to the PRISMA 2020 principles for transparency of search and selection and, because clinical heterogeneity precluded meta-analysis, the Synthesis Without Meta-analysis (SWiM) guideline. PubMed/MEDLINE and public professional society repositories were searched from inception to 6 June 2026, supplemented by hand searching; eligibility was prespecified using a PICOS framework. Study selection and extraction were performed in duplicate. The risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (non-randomized studies). Findings were synthesized narratively across a prespecified evidence hierarchy (direct, indirect, mechanistic). Direct evidence was limited to five studies and was constrained by heterogeneity, small sample sizes in the MRA studies, and moderate-to-serious risk of bias in most non-randomized comparisons. One registry cohort (n = 4,838) reported a U-shaped association between preprocedural potassium and one-year recurrence, with the lowest observed risk at 4.41-4.60 mmol/L; however, this observational association does not establish an optimal therapeutic target or benefit from supplementation. Among four small/heterogeneous MRA studies, eplerenone and a single-center spironolactone randomized trial showed favorable recurrence signals, whereas retrospective esaxerenone showed no recurrence reduction despite improvements in secondary biomarker and remodeling measures; another study used renal sympathetic denervation as an active comparator and therefore did not establish MRA benefit over usual care. These findings should be interpreted cautiously because of study limitations, imprecision, confounding by indication, and variable recurrence ascertainment. Indirect evidence from non-ablation populations and mechanistic studies supports biological plausibility for interactions among potassium homeostasis, mineralocorticoid signaling, renal function, and atrial remodeling, but cannot validate a post-ablation treatment strategy. Accordingly, the proposed ionic-renal-aldosterone-fibrosis axis should be regarded as a hypothesis-generating framework rather than a clinically validated mechanism. Current evidence supports avoiding hypokalemia and hyperkalemia, correcting reversible disturbances, and prescribing MRAs for established indications with appropriate monitoring; it does not justify routine potassium supplementation or MRA use solely to prevent post-ablation recurrence. Prospective, adequately powered randomized studies with longitudinal potassium assessment and rigorous rhythm monitoring are required before mechanism-based post-ablation interventions can be recommended.

Hidradenitis suppurativa is a chronic, inflammatory skin disease that predominantly affects women of reproductive age and may require continuous therapeutic control during pregnancy and lactation. This review summarizes current evidence on the safety and practical use of topical, systemic, biologic, metabolic, and procedural therapies for HS throughout the preconception, gestational, peripartum, and breastfeeding periods. Topical clindamycin, benzoyl peroxide, chlorhexidine, and selected beta-lactam antibiotics appear to represent preferred options for mild disease or acute flares, whereas tetracyclines, retinoids, spironolactone, apremilast, Janus kinase inhibitors, and most glucagon-like peptide-1 (GLP-1) receptor agonists require avoidance or discontinuation because of fetal or neonatal safety concerns. Among biologics, tumor necrosis factor-α inhibitors remain the best-characterized agents, with certolizumab pegol offering minimal placental transfer and adalimumab or infliximab requiring individualized decisions regarding continuation and timing of discontinuation. Evidence for newer agents, including secukinumab and bimekizumab, is evolving but remains more limited. The review also highlights the importance of preconception counseling, medication transition, multidisciplinary delivery planning, postpartum flare prevention, breastfeeding-compatible therapy, and individualized procedural management. The management considerations presented herein are intended to support individualized clinical decision-making and should not be interpreted as formal guideline recommendations.Graphical abstract available for this article.

Mineralocorticoid receptor antagonists (MRAs), aldosterone synthase inhibitors (ASIs), and epithelial sodium channel (ENaC) blockade target different levels of the aldosterone-related sodium-retention pathway in resistant hypertension (RH), but the comparative efficacy of individual agents remains uncertain. We conducted a focused drug-level network meta-analysis of randomized controlled trials (RCTs) comparing pathway-directed therapies in adults with RH. PubMed, Scopus, Embase, Cochrane CENTRAL, Cochrane Reviews, and ClinicalTrials.gov were searched from inception to July 20, 2026. The primary outcome was change in office systolic blood pressure (BP). Secondary outcomes included office diastolic BP and 24-hour ambulatory systolic and diastolic BP. Ten RCTs including 2865 participants were analyzed. In the primary drug-level analysis, amiloride, spironolactone, baxdrostat, eplerenone, and lorundrostat significantly reduced office systolic BP compared with placebo, with mean differences (MDs) of -14.08, -10.78, -9.09, -8.14, and -6.80 mmHg, respectively. Osilodrostat showed a statistically uncertain effect, with an MD of -2.61 mmHg. At the class level, both MRAs and ASIs showed clinically meaningful reductions in office systolic BP. Secondary outcomes were generally consistent with the primary analysis, although fewer trials contributed to these networks. Sensitivity analyses did not materially change the primary findings. These results support the aldosterone-related sodium-retention pathway as an important therapeutic target in RH. MRAs remain the established reference add-on therapy, whereas newer ASIs and amiloride may represent pathway-based alternatives for selected patients. Trial Registration: INPLASY202670099.

Gynecomastia is a benign proliferation of male breast glandular tissue caused by an imbalance between estrogen and androgen activity. Spironolactone, a potassium-sparing diuretic commonly prescribed for edema and ascites in chronic liver disease, is a recognized cause of drug-induced gynecomastia because of its antiandrogenic effects. We report the case of a man in his 50s with chronic liver disease and type 2 diabetes mellitus who presented with bilateral breast swelling and mild tenderness of one month's duration. Clinical examination revealed bilateral soft glandular enlargement without nipple discharge, a hard mass, or axillary lymphadenopathy. Breast ultrasonography demonstrated diffuse fibroglandular proliferation with subareolar thickening consistent with bilateral gynecomastia. Laboratory investigations showed mildly reduced serum testosterone with relative estrogen predominance, while prolactin, luteinizing hormone, follicle-stimulating hormone, and thyroid function tests were within normal limits. Chronic liver disease likely contributed to hormonal imbalance through impaired estrogen metabolism and altered sex hormone regulation, thereby increasing susceptibility to spironolactone-induced gynecomastia. Spironolactone therapy was discontinued, and conservative management with clinical monitoring was advised. The patient showed gradual symptomatic improvement during follow-up. This case highlights the importance of recognizing medication-induced endocrine adverse effects, particularly in patients with chronic systemic illnesses such as hepatic dysfunction.

Aldosterone induces rapid, non-genomic vasodilation of the rat mesenteric vasculature, and mineralocorticoid receptor (MR) antagonists are widely used in cardiovascular disease, yet their pharmacological profiles beyond classical MR blockade remain unclear. We examined whether the G protein-coupled estrogen receptor (GPER/GPR30), functionally coupled to the epidermal growth factor receptor (EGFR), accounts for the rapid endothelial nitric oxide (NO) component of aldosterone action, and whether MR antagonists display intrinsic GPER-linked activity.

Gitelman syndrome (GS) is an inherited salt-wasting, hypokalemic tubulopathy caused mainly by biallelic loss-of-function variants in the SLC12A3 gene. Despite being classically diagnosed in adolescence, delayed recognition may occur. We present the case of a 74-year-old man with a history of hypokalemia, in whom the diagnostic evaluation revealed hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and secondary hyperreninemic hyperaldosteronism, consistent with renal potassium wasting. Given the late presentation, the main challenge was the need to distinguish an inherited tubulopathy from common acquired causes of hypokalemia. Genetic testing was performed, identifying a previously unreported homozygous out-of-frame deletion in exon 25 of the SLC12A3 gene, predicted to result in loss of protein function and therefore to be pathogenic. Treatment with supplementation plus spironolactone achieved sustained biochemical improvement and clinical stability during long-term follow-up. This case highlights that GS should be considered in patients with chronic unexplained hypokalemia regardless of age, and that genetic testing is essential for definitive diagnosis.