Systemic sclerosis (scleroderma) can manifest with advanced symptoms of ischemic vasculopathy, including digital ulcer development. These ulcerations can be disabling and detrimental to a patient's quality of life, so prompt diagnosis, differentiation from other vascular etiologies, and treatment are important to help salvage this tissue. However, diagnosis of scleroderma can be challenging in the setting of seronegative disease. Nailfold capillaroscopy is a vital tool that can assist with diagnosis in seronegative cases. Scleroderma pattern findings on nailfold capillaroscopy include dilated or giant capillaries, capillary hemorrhages, and dropouts. Pharmacologic and surgical modalities can effectively treat vascular complications from scleroderma. Vasodilation therapy with prostacyclin analogs, calcium channel blockers, or angiotensin II receptor blockers can improve ischemic tissue perfusion. Surgical sympathectomy should be offered to treat ulcerative tissue and improve related pain control. We present a case of seronegative scleroderma in a patient with digital ischemic ulcerations that was expediently diagnosed and treated with assistance of nailfold capillaroscopy.

I read with interest the retrospective cohort study by Kleinman et al published in World Journal of Nephrology. Renin-angiotensin-aldosterone system inhibitors (RAASi) anchor therapy for chronic kidney disease, heart failure, and hypertension, but hyperkalemia often curtails optimal use. This letter synthesizes a retrospective cohort of 13447 patiromer users, where approximately 25% high adherers [proportion of days covered (PDC) ≥ 80%] showed approximately 10% greater RAASi utilization (days' supply and PDC) across angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and mineralocorticoid receptor antagonists vs lower adherers. Findings echo OPAL-HK, reinforce Kidney Disease: Improving Global Outcomes 2021 binder prioritization, and urge adherence strategies to sustain guideline therapy, cut hospitalizations, and integrate with SGLT2i/finerenone.

With the alarming rise in the global prevalence of the disease, type 2 diabetes mellitus (T2DM) has recently become the leading cause of chronic kidney disease (CKD) worldwide. Proteinuria, the earliest and common indicator of diabetic kidney disease (DKD), not only increases the risk of progression of CKD to end-stage renal disease (ESRD) but also multiplies the risk of cardiovascular (CV) disease in patients with diabetes. Medications such as angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 inhibitors (SGLT-2is), and mineralocorticoid receptor antagonists (MRAs) have been shown to reduce proteinuria and therefore possess disease-modifying properties in patients with DKD. Clinical trials have demonstrated the efficacy of finerenone, a highly selective, non-steroidal MRA, in reducing renal and CV outcomes in patients with long-standing T2DM. The benefits of various SGLT-2is have also been observed in multiple studies. Therefore, a combination of these medications, with independent but complementary mechanisms of action, could provide superior benefits as add-on therapies to ACEis/ARBs rather than using either alone. This Opinion Review explores disease-modifying strategies in patients with DKD based on the most up-to-date evidence.

Cardiovascular risk factors are often undertreated in patients with dementia. Renin-angiotensin system inhibitors (RASI) are first-line treatments for hypertension. We examined the association between RASI and all-cause mortality in hypertensive patients with and without dementia, comparing angiotensin-converting enzyme inhibitors (ACEI) to angiotensin receptor blockers (ARB); and selected individual agents. This nationwide register-based cohort study included data from Swedish national registries 2007-2018. The study included 158 176 hypertensive patients with exposure to RASI medications (21 152 RASI users and 137,024 non-users), after excluding prevalent users. Propensity score matching was used to balance measured confounders. Cox regressions compared mortality risk among RASI users versus non-users, ACEI users versus ARB users, and users of enalapril, ramipril, losartan, and candesartan versus other RASI users. RASI use was associated with lower all-cause mortality (hazard ratio[HR] 0.93, 95% confidence interval[CI] 0.91-0.95, p< 0.001) in the full cohort, and among patients with dementia (HR 0.88, 95% CI 0.85-0.92). Compared to ACEI, ARB were associated with lower mortality in the full cohort (HR 0.90, 95% CI 0.85-0.96), but results were not significant in patients with dementia. The comparison of the individual drugs were consistent with class-level findings. RASI use was associated with lower all-cause mortality among older hypertensive patients, including those with dementia. These observational findings support continued attention to evidence-based hypertension treatment in patients with dementia.

Sudden cardiac death (SCD) is a leading cause of mortality across the chronic kidney disease (CKD) continuum and becomes particularly prominent in dialysis-dependent kidney failure. In hemodialysis, SCD accounts for roughly one quarter to one third of all deaths and up to 60%-75% of cardiovascular mortality, with marked temporal clustering around the long interdialytic interval and the first post-interval session. Traditional views have emphasized descriptive epidemiology and presumed ventricular tachyarrhythmias. More recent device-based studies challenge this paradigm, revealing a heterogeneous arrhythmic spectrum in which bradyarrhythmias, pauses, and conduction system disease are often at least as frequent as sustained ventricular tachycardia or fibrillation. This narrative, non-systematic review synthesizes epidemiologic, mechanistic, and interventional data on SCD in CKD and dialysis, with particular emphasis on insights from implantable loop recorder and implantable cardioverter-defibrillator cohorts and on modifiable dialytic and pharmacologic factors. A framework for prevention is proposed around three interacting domains: the structural myocardial substrate, the electrophysiologic milieu, and dialysis-related triggers. Within this framework, contemporary heart failure and CKD therapies (including sodium-glucose cotransporter 2 inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, and beta-blockers), individualized dialysis prescriptions (targeting potassium, calcium, bicarbonate, ultrafiltration, and scheduling), and selective use of device therapy are considered complementary components of mechanism-driven SCD prevention. Methodological challenges in defining and adjudicating SCD in CKD are discussed, and priorities are outlined for improved phenotyping, continuous rhythm monitoring, and CKD-specific risk stratification, with the overarching aim of moving from descriptive statistics to effective risk modification.

Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently coexist, share risk factors and pathophysiology, and confer a high burden of stroke, bleeding, heart failure, and premature death. Risk scores such as CHA2DS2-VASc, which estimates thromboembolic risk, and HAS-BLED, which estimates bleeding risk, were derived in populations including relatively few patients with advanced CKD. Consequently, they may not adequately account for CKD-specific modifiers of thromboembolic and hemorrhagic risk. Although these scores do not formally incorporate competing non-stroke mortality, higher CHA2DS2-VASc scores may indirectly identify patients with a greater competing risk of death. Meanwhile, widespread use of renin-angiotensin-aldosterone system blockade, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide‑1 receptor agonists has reshaped cardiorenal prognosis, further challenging historical calibrations of stroke and bleeding scores. In this perspective, we critically appraise conventional risk scores in AF with CKD, highlight their limitations in the context of modern preventive therapies and competing mortality, and outline priorities for more dynamic, kidney‑focused risk stratification.

Post-COVID syndrome is predominantly characterized by persistent fatigue that cannot be attributed to other underlying diseases or relieved by conventional rest. Such symptoms may last for weeks to months, substantially impairing patients' health status and quality of life. Nevertheless, current understanding of the pathogenesis of post-COVID syndrome remains insufficient, posing major challenges to its effective clinical management. Therefore, this review elaborates comprehensively on the pathogenesis, potential therapeutic targets, and pharmacological interventions for post-COVID syndrome, aiming to provide evidence for drug research and development as well as clinical application. Four interrelated pathogenic mechanisms sustaining chronic inflammation after viral clearance are collectively involved in disease progression, including immune dysregulation accompanied by chronic low-grade inflammation, mitochondrial dysfunction and impaired energy metabolism, renin-angiotensin system imbalance, and gut microbiota dysbiosis with disrupted gut-brain axis function. Based on these mechanistic findings, this review highlights potential therapeutic targets such as TLR4/TLR7, the JAK/STAT pathway, the NLRP3 inflammasome, the AMPK/NRF2 axis, and the PINK1/Parkin pathway. Accordingly, we summarize mechanism-targeted candidate drugs, including Toll-like receptor antagonists, JAK inhibitors, probiotics, mitochondria-targeted agents and drugs correcting renin-angiotensin system imbalance. In addition, this review summarizes other therapeutic candidates acting via distinct mechanisms, such as fluvoxamine, coenzyme Q10 combined with alpha-lipoic acid, astragalus root extracts, other medicinal herbs and traditional Chinese compound formulas. Post-COVID syndrome represents a complex public health challenge. Further in-depth mechanistic research and rational application of emerging technologies are still required to develop therapeutic strategies for preventing and alleviating the onset and progression of post-COVID syndrome.

In recent years, studies have been carried out that have expanded the understanding of the role of pathophysiological mechanisms underlying impaired regulation of aldosterone and activation of mineralocorticoid receptors in arterial hypertension. The aim of this consensus is to consider the association between aldosterone dysregulation and the development of cardiovascular complications, as well as to assess the effectivity and safety of novel nonsteroidal mineralocorticoid receptor antagonists, to expand the understanding of their potential in ensuring the prevention of target organ damage and cardiovascular complications in the treatment of patients with hypertension, to analyze the potential of a new class of drugs - aldosterone synthase inhibitors - in ensuring the suppression of genomic and non-genomic effects of aldosterone and their adverse effects in patients with hypertension, to assess the efficacy of drug therapy including nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors in the category of patients at high cardiovascular risk - in hypertension due to primary hyperaldosteronism.

Co-treatment with ACE inhibitors/angiotensin II receptor antagonists was obligatory and an aldosterone antagonist optional in trials that established efficacy of β1 adrenergic receptor (β1AR) antagonists in heart failure with reduced ejection fraction (HFrEF). However, with worsening HFrEF, combination treatment is often not tolerated, and patients receive β1AR antagonists only. It cannot be assumed monotherapy is efficacious and might even be harmful because a raised myocardial cytosolic Na[+] concentration ([Na[+]c]) in HFrEF reduces myocardial contractility while β1AR-coupled signaling has been widely reported to activate myocyte Na[+]-K[+] pump-mediated Na[+]c export in previous studies. We ligated the circumflex coronary artery of rabbits or performed sham thoracotomy. Rabbits with left ventricular ejection fraction <25% seven days after coronary ligation were treated with the β1AR antagonist metoprolol or vehicle. Metoprolol reduced heart rate of sham-operated rabbits but not of rabbits that had coronary ligation. Metoprolol had no effect on systolic-, diastolic- or mean blood pressures in either group. The primary index for heart failure, lung: body weight ratios, was ~89% higher after coronary ligation than after sham thoracotomy and metoprolol significantly reduced this to a ~46% difference. The index for Na[+]-K[+] pump function, electrogenic pump current (Ip), increased for myocytes from sham-operated rabbits. For myocytes from rabbits that had coronary ligation, metoprolol reversed a 63% decrease of Ip. Results are consistent with enhanced Na[+]-K[+] pump-mediated Na[+]c export in HFrEF contributing to efficacy of β1AR antagonist monotherapy independent of heart rate and afterload but does not support β1AR-coupled cAMP signaling increasing cardiac Na[+]-K[+] pump activity.

Development of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) is a dual threat, imposing not only increased risk for end-stage renal disease, but also substantially increasing cardiovascular risk and premature mortality[1]'[3]. Its prevalence is staggering, affecting approximately 30-40% of all patients with T2DM[1]. Fortunately, advances in pharmacotherapies over the past twenty-five years, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (nsMRAs), and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) together with blockade of renin angiotensin aldosterone system activation (RAAS) with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs), have transformed the clinical management of T2DM and CKD[2]. By providing parallel reductions in both renal and cardiovascular risk, patients with T2DM and CKD (especially those at higher risk), experience improved survival, fewer cardiovascular events and require less initiation of dialysis as a result of delayed progression to end-stage renal failure[9]-[14]'[19]. Recent evidence from clinical trials in T2DM and CKD, supports simultaneous use of combinatory phamacotherapies targeting distinct mechanistic pathophysiological pathways[19].

Primary aldosteronism (PA) and obstructive sleep apnea (OSA) are common but often unrecognized contributors to hypertension. When they coexist, aldosterone excess, fluid redistribution, intermittent hypoxia, sympathetic activation, and shared metabolic risk may increase hypertension-mediated organ damage. This narrative review examines the evidence linking PA and OSA, with emphasis on mechanisms, cardiovascular and renal consequences, diagnostic limitations, and clinical management. Aldosterone-related sodium retention and nocturnal rostral fluid shift may worsen upper-airway obstruction. Conversely, intermittent hypoxia, sleep fragmentation, and sympathetic activation in OSA may alter renin-angiotensin-aldosterone system activity, although OSA does not account for autonomous aldosterone secretion. Both disorders are associated with oxidative stress, inflammation, endothelial dysfunction, cardiac remodeling, and renal injury. Their overlap should be considered in patients with resistant hypertension, hypokalemia, adrenal incidentaloma, clinically suspected OSA, or organ damage not fully explained by measured blood pressure. Management requires independent confirmation of each disorder, subtype-directed PA treatment with adrenalectomy or mineralocorticoid receptor antagonists, and appropriate OSA treatment with positive airway pressure or other individualized measures. Multidisciplinary care may improve blood pressure and intermediate organ outcomes, but prospective studies are needed to determine whether combined treatment reduces long-term cardiovascular, renal, and cerebrovascular events.