Search Results (201)

Background/Objectives: Esaxerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA) with potent cardiorenal protective effects. However, the clinical effects of switching from eplerenone to esaxerenone in patients with chronic heart failure complicated by hypertension remain unclear. This study investigated the effects of switching from eplerenone to esaxerenone on blood pressure, heart failure biomarkers, renal function, and the renin–angiotensin–aldosterone system (RAAS). Methods: A total of 156 patients with chronic heart failure and hypertension who had been receiving eplerenone for more than one year were prospectively enrolled. Eplerenone was switched to esaxerenone, and the patients were followed for 6 months. Blood pressure, heart rate, brain natriuretic peptide (BNP), renal function, urinary albumin-to-creatinine ratio (UACR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary osmolality (U-OSM) were evaluated. Results: Following the switch to esaxerenone, systolic and diastolic blood pressure significantly decreased (both p < 0.001), whereas heart rate remained unchanged. BNP levels significantly decreased at 3 and 6 months (p = 0.008 and p = 0.002, respectively). Serum creatinine decreased (p = 0.017), estimated glomerular filtration rate increased (p = 0.028), and UACR significantly decreased at both time points (both p < 0.001). PRA and PAC significantly increased after switching (both p < 0.05), whereas angiotensin II levels remained unchanged. U-OSM significantly decreased (p = 0.01 and p = 0.002 at 3 and 6 months, respectively). No major cardiovascular events or severe adverse events were observed. Conclusions: In patients with chronic heart failure and hypertension, switching from eplerenone to esaxerenone was associated with reductions in blood pressure, BNP, UACR, and urinary osmolality, together with improvements in renal function. These findings suggest favorable physiological changes following the switch from a steroidal to a non-steroidal mineralocorticoid receptor antagonist, although confirmation in randomized controlled studies with clinical outcome measures is warranted. Full article

Background/Objectives: Hyperuricemia is highly prevalent in chronic kidney disease (CKD). It has been linked to increased cardiovascular and mortality risk. However, its independent prognostic significance and dose–response relationship with adverse outcomes remain incompletely understood. Methods: This retrospective cohort study included 794 patients with CKD. Hyperuricemia was defined using sex-specific thresholds. The association between hyperuricemia, cardiac events and mortality was tested using a multivariable logistic regression test. Serum uric acid was analyzed as both a categorical and a continuous variable to assess dose–response relationships. Results: Hyperuricemia was present in 44.8% of patients. In multivariable analysis, hyperuricemia was associated with increased odds of cardiac events, although this did not reach statistical significance (OR 1.49, 95% CI 0.98–2.27, p = 0.061). However, hyperuricemia independently predicted mortality (OR 1.98, 95% CI 1.04–3.78, p = 0.039), and importantly, a dose–response relationship was observed between serum uric acid and adverse outcomes. Each 100 μmol/L increase in serum uric acid was associated with a 22% increase in cardiac event risk (OR 1.22, p = 0.011) and a 29% increase in mortality risk (OR 1.29, p = 0.004). Quartile analysis revealed that patients in the highest uric acid quartile had more than three-fold higher mortality compared with the lowest quartile (OR 3.13, 95% CI 1.26–7.79, p = 0.014). Conclusions: Hyperuricemia independently predicts mortality and also demonstrates a significant dose–response relationship with adverse outcomes in CKD. The results support serum uric acid as a clinically meaningful biomarker for mortality risk grading in CKD populations. Full article

Chronic kidney disease, acute kidney injury and cardiorenal syndrome are major determinants of cardiovascular morbidity and mortality, yet conventional renal assessment based on serum creatinine, estimated glomerular filtration rate and urine output often fails to detect early structural injury or pathway-specific cardiorenal risk. This narrative review synthesized recent evidence on emerging renal and cardiorenal biomarkers with potential value for cardiovascular risk stratification beyond creatinine. Literature published between 2015 and April 2026 was reviewed, focusing on biomarkers of tubular injury, functional renal impairment, fibrosis/remodeling and mineral metabolism. NGAL and KIM-1 may detect tubular stress and proximal tubular injury before overt functional decline and have shown relevance in heart failure, acute coronary syndromes and post-cardiac surgery settings. Cystatin C and pro-enkephalin refine functional renal assessment and may improve prognostic classification when creatinine is confounded by frailty, muscle mass or acute hemodynamic changes. Soluble ST2 and galectin-3 reflect inflammation, fibrosis and cardiorenal remodeling, while FGF-23 links kidney dysfunction to cardiovascular risk through phosphate imbalance, vascular calcification and myocardial hypertrophy. Multi-biomarker panels may help identify dominant cardiorenal phenotypes and personalize monitoring intensity. However, routine implementation requires standardized assays, validated thresholds, cost-effectiveness data and prospective evidence that biomarker-guided management improves clinical outcomes. Full article

The recently conceptualized Cardiovascular–Kidney–Metabolic (CKM) syndrome represents a pressing global health burden, characterized by a vicious cycle of dysfunction among the cardiac, renal, and metabolic systems. Growing evidence suggests that gut microbiota dysbiosis, specifically, a loss of butyrate-producing bacteria (BPB) and the resulting systemic butyrate deficiency, may be an important but previously overlooked driver of CKM progression. In this review, we synthesize available evidence linking butyrate to the integrated, multi-organ pathophysiology of CKM and propose a conceptual framework we term the gut-butyrate-CKM axis. We discuss the multiple mechanisms by which butyrate and BPB exert protective effects, including targeting key pathophysiological features of CKM, such as insulin resistance (IR), metabolic inflammation, oxidative stress, endothelial dysfunction, renin–angiotensin–aldosterone system (RAAS) overactivation, and gut dysbiosis itself. Through a critical appraisal of human studies, we bring together findings from direct butyrate supplementation, dietary interventions, and microbiota-directed strategies. Based on this, we argue that butyrate serves as a central hub linking gut homeostasis to systemic metabolic and cardiorenal health. By integrating previously fragmented observations into a coherent framework, this review addresses a conceptual gap in our understanding of CKM pathogenesis and points to actionable, microbiota-targeted therapeutic strategies that could help break the disease cycle. Given the current lack of integrated management options for CKM, our work offers insights for future translational research and clinical practice, highlighting butyrate-centered approaches as a potential paradigm shift in CKM care. Full article

Background: Hyperhomocysteinemia (homocysteine [Hcy] ≥15 μmol/L) is frequently observed in patients with impaired kidney function and has been associated with vascular remodeling and increased cardiovascular risk. We aimed to evaluate the relationship between Hcy, arterial stiffness, coronary artery disease (CAD), peripheral arterial disease, and biomarkers of kidney injury in patients undergoing elective coronary angiography. Methods: In this prospective observational study, 133 patients undergoing elective coronary angiography were stratified according to serum Hcy levels (Hcy <15 vs. Hcy ≥15 μmol/L). CAD severity was assessed angiographically. Arterial stiffness was evaluated using carotid–femoral pulse wave velocity (cfPWV), while peripheral arterial disease was assessed using ankle–brachial index (ABI). Kidney function was evaluated using serum creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin-to-creatinine ratio (UACR). Correlation, multivariable regression, logistic regression, and receiver operating characteristic (ROC) analyses were performed. Results: Patients with hyperhomocysteinemia demonstrated significantly worse kidney function, including higher serum creatinine, cystatin C, and UACR levels, and lower eGFR (all p < 0.01). Patients with elevated Hcy levels also exhibited significantly higher cfPWV values (11.4 ± 3.3 vs. 9.7 ± 2.1 m/s, p < 0.001). Hcy correlated positively with cystatin C, creatinine, UACR, and cfPWV, and inversely with eGFR. In multivariable linear regression analysis, Hcy remained independently associated with increased cfPWV after adjustment for age, sex, and eGFR (β = 0.137, 95% CI 0.047–0.226, and p = 0.003). This association remained significant in sensitivity analyses incorporating hypertension, diabetes mellitus, LDL cholesterol, and statin therapy (β = 0.124, 95% CI 0.032–0.216, and p = 0.008). No independent associations were observed between Hcy and angiographic CAD severity or ABI values. ROC analysis demonstrated modest discrimination for elevated arterial stiffness (AUC = 0.66, 95% CI 0.56–0.76) and good discrimination for impaired kidney function (AUC = 0.82, 95% CI 0.69–0.92). Conclusions: Elevated Hcy levels were independently associated with impaired kidney function and increased central arterial stiffness, but not with angiographic CAD severity or peripheral arterial disease. These findings suggest that hyperhomocysteinemia may reflect cardiorenal vascular dysfunction and diffuse vascular remodeling rather than focal obstructive atherosclerotic disease. Further studies are needed to determine its clinical utility and prognostic value. Full article

Congestion is a major driver of symptoms, hospitalization, and adverse outcomes in heart failure (HF), yet its clinical assessment remains challenging. Traditional approaches based on physical examination, biomarkers, and isolated imaging surrogates often fail to capture the complexity of systemic venous congestion and its impact on organ function. In HF, congestion should be interpreted as a multifactorial process resulting from the interaction between intravascular volume burden, venous compliance, cardiac filling pressures, neurohormonal activation, blood volume redistribution, and organ-specific susceptibility. In this context, point-of-care ultrasound has emerged as a promising adjunctive tool for bedside congestion assessment. The Venous Excess Ultrasound (VExUS) score integrates inferior vena cava assessment with Doppler analysis of hepatic, portal, and intrarenal veins, allowing for the evaluation of venous pressure transmission and organ-level congestion. Observational studies suggest that VExUS and related venous Doppler abnormalities correlate with invasive hemodynamic parameters and are associated with acute kidney injury, diuretic response, heart failure hospitalization, and mortality. Serial changes in venous congestion may provide additional information regarding treatment response and clinical trajectory. However, the available evidence remains heterogeneous across acute HF, ambulatory HF, cardiorenal syndrome, and critical care populations, and randomized trials evaluating VExUS-guided management are lacking. Therefore, VExUS should be interpreted as a complementary tool within a multimodal assessment that includes echocardiography, lung ultrasound, biomarkers, renal function, urine output, physical examination, and response to therapy. By integrating fluid burden with venous pressure transmission and organ perfusion, multimodal ultrasound may support more individualized congestion assessment and risk stratification in HF. Full article

Cardiovascular–kidney–metabolic (CKM) syndrome is a systemic, interdependent disorder arising from the convergence of metabolic dysfunction, chronic kidney disease, and cardiovascular pathology. Anchored in the Developmental Origins of Health and Disease (DOHaD) framework, this review advances a “parallel hit” model, primarily based on evidence from experimental animal studies, particularly rodent models, posited that early-life environmental insults concurrently program structural and functional vulnerabilities in both renal and central nervous system hubs. These early perturbations prime susceptibility long before clinical manifestations emerge. CKM progression is conceptualized as a two-stage trajectory, with an initial phase of parallel programming affecting kidney and brain development, followed by a transition to maladaptive bidirectional crosstalk. In the later phase, heightened efferent sympathetic outflow and aberrant afferent renal signaling—potentiated by uremic toxin accumulation, neuroinflammation, and blood–brain barrier disruption—drive a self-perpetuating cycle that accelerates cardiorenal and metabolic injury. Key integrative mechanisms, including oxidative stress, chronic low-grade inflammation, mitochondrial dysfunction, and gut microbiota dysbiosis, serve as convergent pathways linking early-life exposures to adult CKM phenotypes. These pathways not only sustain disease progression but also represent actionable therapeutic targets. Importantly, this framework underscores the translational potential of early-life “reprogramming” strategies. Interventions such as precision nutrition, antioxidant supplementation, microbiota-directed therapies (including prebiotics, probiotics, and postbiotics), and mechanism-based pharmacotherapies may mitigate or reverse maladaptive programming. However, much of the current mechanistic evidence remains preclinical, and further human studies are needed to validate these pathways and therapeutic approaches. Collectively, this dual-hub paradigm reframes CKM syndrome as a life-course continuum rather than a late-stage comorbidity cluster, emphasizing the necessity of early, mechanism-driven interventions to stabilize the brain–kidney axis and improve long-term cardiovascular–kidney–metabolic outcomes. Full article

Treating autosomal dominant polycystic kidney disease (ADPKD) has always been a challenge because the disease is too complex for single-target drugs, which are often held back by side effects. This narrative review explores a different strategy: using plant-derived polyphenols to target multiple disease pathways at the same time. Looking at research from 2005 to 2026, we break down how key compounds like resveratrol, curcumin, naringenin, quercetin, and epigallocatechin-3-gallate (EGCG) actually work. Preclinical studies show these molecules can slow down cyst growth by tackling inflammation, rapid cell division, and tissue scarring all at once, while also resetting the skewed energy metabolism of cystic cells. Some mechanisms are strikingly specific, such as naringenin’s direct interaction with polycystin-2 and quercetin’s ability to clear senescent cells. Yet, the real-world hurdle is poor absorption; a recent clinical trial with standard curcumin fell short simply because the compound could not reach the kidneys in high enough concentrations. Moving forward, the field needs to focus on testing these compounds in realistic animal models, designing smart nanoformulations to improve bioavailability, and exploring combinations that could safely complement current therapies like tolvaptan. Full article

Circular RNAs have emerged as important regulators of gene expression in cardiovascular disease, expanding the current understanding of the molecular mechanisms that underlie cardiac remodeling and dysfunction. Initially regarded as byproducts of aberrant splicing, circRNAs are now recognized as stable, abundant, and functionally versatile molecules with marked tissue specificity and diverse modes of action. In the cardiovascular system, circRNAs are generated through tightly regulated back-splicing mechanisms and act through multiple molecular pathways, including microRNA sequestration, protein scaffolding, modulation of transcription and splicing, regulation of mitochondrial and metabolic homeostasis, and in some cases, peptide translation. These properties position circRNAs as regulatory hubs that connect molecular interactions to functional cellular outcomes. Across a broad range of cardiovascular conditions, including heart failure, myocardial ischemia, fibrosis, arrhythmias, cardiotoxicity, and cardiorenal syndrome, circRNAs have been implicated in processes such as hypertrophy, inflammation, cell death, extracellular matrix remodeling, and regenerative responses. Beyond their mechanistic relevance, circRNAs also hold preclinical relevance as circulating biomarkers and therapeutic targets owing to their stability in biofluids and their capacity to modulate disease-relevant networks. Nevertheless, major challenges remain, including incomplete functional validation, methodological heterogeneity, annotation inconsistencies, and barriers to clinical translation. In this review, we synthesize the current knowledge on circRNA biogenesis, molecular function, disease-specific roles, biomarker potential, and therapeutic applications and discuss the conceptual and technical advances required to move the field from descriptive association toward mechanistic and clinical impact. Full article

Cardiorenal Syndrome (CRS) types depend on the primary impaired organ, Heart (Types I/II) or Kidney (Types III/IV), and are chronic (Types II/IV) or acute (Types I/III). Type V associates to a systemic disease. Diagnosis of CRS type via biochemical indices (e.g., B-type-natriuretic-peptide (BNP), neutrophil-gelatinase-associated-lipocalin (NGAL)) has not been documented absolutely, until now. Here we used advanced imaging facilities, atomic force microscope (AFM) and scanning electron microscope (SEM) for the biopsy of peripheral blood smears coming from CRS patients, aiming to investigate the possible existence of cellular indices associated with CRS pathology. Standard biochemical and hematological indices were comparatively recorded. Cylindrical micro/nano-metric Vesicles (mnVs) were observed in all CRS patients. In CRS patients with Types III/IV, the AFM/SEM data revealed an increased mnVs population and activated platelets that may represent their potential parent cells. In these patients, increased basic uraemic indices and BNP and NGAL levels were also observed. On the contrary, in patients with CRS Types I/II/V, the AFM/SEM data showed a comparatively smaller mnVs population, accompanied by lower levels of BNP and NGAL. According to our results, a higher mnVs population was observed in CRS Types III/IV, possibly released from platelets. The mnVs population may be associated with basic uraemic indices and increased BNP and NGAL levels. Full article

Background and Objectives: To investigate prognostic risk factors and determine the incidence, clinical characteristics, and predictors of heart failure (HF) development in pediatric patients with end-stage kidney disease (ESKD) secondary to steroid-resistant nephrotic syndrome (SRNS). Materials and Methods: We conducted a retrospective cohort study of pediatric patients diagnosed with ESKD secondary to nephrotic syndrome (NS) between 2014 and 2020. Patients were stratified based on clinical outcomes and the occurrence of HF during follow-up. Comparative analyses of clinical characteristics, laboratory parameters, and cardiac assessments were performed across groups. Multivariate logistic regression was used to identify independent risk factors for HF development within the first year and for adverse prognosis at five years. Results: The cohort comprised 172 children with ESKD secondary to NS. Multivariate logistic regression identified HF as an independent risk factor for adverse long-term outcomes in pediatric patients with ESKD. During follow-up, HF developed in 27 patients (15.7%) within the first year after ESKD diagnosis, and in 45 patients (26.2%) by the end of five years. Early HF onset (within the first year) was associated with a significantly reduced five-year survival rate. Independent risk factors for HF development included elevated cardiac troponin I levels (OR = 6.786, 95% CI: 2.326–19.799), a history of cardiac arrhythmias (OR = 2.951, 95% CI: 1.260–6.912), and the presence of left heart enlargement (OR = 23.669, 95% CI: 2.876–194.827), and valvular regurgitation at the initial post-ESKD diagnosis evaluation. Conclusions: HF is associated with markedly reduced survival. Crucially, our findings demonstrate that pre-existing cardiovascular structural abnormalities—specifically left heart enlargement—and elevated cTnI are robust, early predictors of HF. These findings necessitate a paradigm shift in pediatric ESKD management, we advocate for the implementation of systematic baseline echocardiographic and biomarker screening at the immediate onset of ESKD. Identifying these subclinical, yet modifiable, structural changes provide a critical therapeutic window for targeted anti-remodeling interventions to significantly improve long-term prognosis. Full article

Cardiorenal–metabolic (CKM) syndrome has emerged as a unifying condition describing the interplay between metabolic dysfunction, chronic kidney disease, and cardiovascular disease. To address this concept, the American Heart Association, in a 2023 Presidential Advisory, presented an official statement to capture the transition from metabolic risk and subtle cardiorenal dysfunction to overt cardiovascular and renal disease. Although this framework provides a structured representation of disease burden and facilitates risk stratification, emerging evidence suggests that it is primarily focused on the progressive nature, whereas high-risk patients may experience sudden cardiac or renal events. While staging systems provide important tools for risk stratification, they remain primarily descriptive and do not adequately reflect the dynamic and non-linear interactions underlying disease progression. Importantly, patients exhibit substantial heterogeneity in dominant pathophysiological drivers, related to various baseline risk factors and primitive cardio–kidney disorders, that is not fully captured by stage-based classifications. Notably, we propose a phenotype-oriented approach to CKM syndrome based on the recognition that its clinical expression reflects heterogeneous and evolving pathophysiological mechanisms rather than a uniform disease trajectory. According to this strategy, the paradigm of management shifts from an evolutive concept to a more appropriate use of disease modifying agents with cross-organ effects. Sodium–glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1a), and non-steroidal mineralocorticoid receptor antagonists (MRA) have demonstrated the ability to modulate key biological pathways across the cardiovascular, renal, and metabolic axes. Therefore, personalized management that identifies a specific strategy according to CKM phenotypes must be assessed. Full article

The therapeutic landscape for heart failure (HF), particularly in patients with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF), has historically been characterized by limited effective disease-modifying options. The recent approval of nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), specifically finerenone, represents a major paradigm shift. This review synthesizes contemporary evidence, including the landmark FINEARTS-HF trial, which demonstrated significant reductions in cardiovascular death and heart failure hospitalizations in patients with left ventricular ejection fraction (LVEF) ≥ 40%. These findings contrast with the neutral overall results and subgroup limitations observed with steroidal MRAs such as spironolactone in the TOPCAT trial. Mechanistic distinctions, cardiorenal benefits, and emerging metabolic effects of finerenone are explored alongside its complementary role with sodium–glucose cotransporter-2 (SGLT2) inhibitors. Practical considerations for implementation, including patient selection, dosing, monitoring, and combination therapy strategies, are discussed. Overall, nsMRAs establish a new foundation for the management of HFmrEF and HFpEF and represent a critical advancement in contemporary heart failure therapeutics. Full article

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases worldwide and remains associated with substantial morbidity, mortality, and limited therapeutic efficacy. This persistent therapeutic gap reflects not only clinical heterogeneity but also a fundamental conceptual limitation: HFpEF has been approached as a myocardial disorder despite mounting evidence that it represents a multisystem syndrome. In this perspective, we integrate current pathophysiological and clinical evidence into a mechanistically anchored endotype framework based on dominant biological axes. We propose four overlapping endotypes—cardiorenal, fibrotic–inflammatory, metabolic–adiposity, and microvascular–energetic—and align contemporary and emerging therapies with these domains. We further outline a pragmatic roadmap for biomarker-guided stratification and propose principles for next-generation clinical trial design based on mechanistic enrichment. This framework provides a clinically actionable structure for biomarker-guided stratification and supports mechanism-based therapeutic selection in HFpEF. Aligning dominant biological drivers with targeted interventions generates testable hypotheses for endotype-enriched clinical trials and precision treatment strategies. Prospective validation of this approach may facilitate a transition from uniform management toward individualized, biology-driven care. Full article

CRS type 1 (CRS-1) is defined as acute kidney injury (AKI) caused by acute decompensated heart failure (ADHF). HF is divided into three subtypes according to the value of ejection fraction (EF). HF with preserved ejection fraction (HFpEF) is an increasingly prevalent subtype of heart failure. A significant number of patients with HFpEF during episodes of acute decompensation (ADHFpEF) develop CRS-1. The objective of this narrative review is to summarize the data about the epidemiology, pathophysiological mechanisms, therapy, and prognostic impact of CRS-1 in patients with ADHFpEF. The most important pathophysiological mechanisms leading to the development of CRS-1 in these patients are hemodynamic disturbances and inflammation. Loop diuretics alone or in combination with other diuretics are the mainstay therapeutic option for treating congestion in patients with CRS-1. Introducing SGLT-2 inhibitors as soon as clinically possible has a positive impact on prognosis. CRS-1 is an independent predictor of a worse outcome in patients with ADHF, although this impact appears to be less associated in patients with HFpEF, than in patients with ADHF with reduced EF. Further studies are needed to better clarify pathophysiological mechanisms and develop treatments that improve cardiorenal outcomes in these patients. Full article