Search Results (155)

The cardiovascular risk imposed by chronic kidney disease is significantly enhanced, and carotid atherosclerosis is an early indicator of systemic vascular damage. In this review, we summarize available data relative to primary prevention strategies for carotid atherosclerosis in chronic kidney disease (CKD) with a focus on risk-adapted and stage-specific management. We conducted a narrative review of the literature. A structured literature search was performed in major databases (PubMed, Scopus, Web of Science and Google Scholar), focusing on studies published between 2012 and 2025, including observational studies, randomized controlled trials, and international guideline recommendations. The review focuses on blood pressure management, lipid-lowering therapy, glycemic control, antiplatelet therapy, as well as lifestyle interventions and screening strategies in patients with CKD without a history of cerebrovascular events. CKD-specific processes, such as inflammation, endothelial dysfunction and vascular calcification, may influence the progression of carotid plaques, highlighting the need to improve traditional and non-traditional risk factor management. The focus of prevention continues to emphasize blood pressure (BP) and lipid control as well. At the same time, routine carotid screening and systematically implemented antiplatelet therapy have no known benefit, but the potential for elevated bleeding risk, especially in advanced CKD. Primary prevention should therefore focus on optimal medical treatment, as well as disease-specific strategies according to CKD stage. Additional CKD-specific studies with carotid endpoints are necessary. Full article

Background/Objectives: Vascular calcification and arterial stiffness are common in chronic kidney disease (CKD). Gla-rich protein (GRP) is a vitamin K-dependent protein implicated in mineral biology, but clinical evidence across CKD stages is limited. We evaluated associations of serum GRP with vascular calcification (VC) burden and arterial stiffness across CKD stages, including hemodialysis, compared with controls. Methods: In this prospective observational study, 185 adults were enrolled: controls (n = 61), individuals with CKD stage IIIb–IV (n = 61), and individuals with CKD stage V on hemodialysis (HD) (n = 63). Abdominal aortic calcification was assessed by the Kauppila score, and arterial stiffness was assessed by oscillometric pulse wave velocity (PWV). Serum GRP, FGF-23, and β-Klotho (KLb) were measured by ELISA. Non-parametric group comparisons and Bonferroni-corrected Spearman correlations were used. Results: GRP differed across groups (p < 0.001), showing a non-linear pattern with the lowest values in CKD IIIb–IV. PWV and Kauppila score increased across CKD stages (both p < 0.001). After Bonferroni correction, GRP correlated with KLb (ρ = 0.720) and FGF-23 (ρ = 0.625), but not with PWV or Kauppila score. In multivariable analyses, GRP showed a statistically significant but modest association with PWV and Kauppila score. Conclusions: In this CKD spectrum cohort, serum GRP was associated with CKD-MBD biochemical markers (KLb and FGF-23) much more strongly than with vascular phenotypes; its associations with vascular calcification burden and arterial stiffness were modest in multivariable modelling, supporting GRP as a marker of the CKD-MBD biochemical profile rather than a strong surrogate of vascular phenotype. Full article

Myocardial calcification is an uncommon complication associated with end-stage chronic kidney disease (CKD) in feline patients. This report describes the clinical and multimodal imaging features of metastatic calcification in a 10-year-old castrated male mixed-breed cat. The patient presented with dyspnea and anorexia, and was diagnosed with IRIS Stage 4 CKD. Laboratory findings revealed severe hyperphosphatemia and an elevated calcium–phosphorus product (CPP) of 135 mg²/dL², based on total calcium. This value significantly exceeds 70 mg²/dL², a threshold associated with a high probability of inducing soft tissue mineralization. Echocardiography revealed extensive hyperechoic foci with posterior acoustic shadowing in the interventricular septum and left ventricular wall. Functional assessment demonstrated a restrictive diastolic filling pattern, suggesting increased myocardial stiffness and congestive heart failure. Computed tomography (CT) further visualized systemic involvement, showing diffuse, amorphous calcifications (400–900 HU) in the myocardium, multifocal aortic wall, and extracardiac tissues. Despite intensive treatment with diuretics and renal support, the patient was euthanized eight days later due to progressive renal failure. This case illustrates that the interaction between metastatic calcification and uremic cardiomyopathy (UC) can result in refractory heart failure, underscoring the value of combined echocardiography and CT in evaluating end-stage renal disease. Full article

Hypertension and chronic kidney disease (CKD) are closely linked conditions and represent common global health problems. Hypertension is a leading risk factor for cardiovascular disease, which is the main cause of mortality in CKD. Endothelial injury underlies the etiopathogenesis of both hypertension and CKD. The endothelial glycocalyx (eGC) is a dynamic, negatively charged, carbohydrate-rich layer that covers the luminal surface of endothelial cells. Its primary physiological function is to protect the endothelium, including the regulation of vascular permeability and homeostasis. Damage to the eGC, known as “shedding”, is an early predictor of endothelial dysfunction and is driven by oxidative stress and low-grade inflammation. In hypertension, loss of eGC integrity—often impaired by a high-salt diet—can reduce the bioavailability of nitric oxide (NO) and increase arterial stiffness. Similarly, in CKD, uremic toxicity, hypertension, and inflammation damage the eGC, resulting in increased permeability, albuminuria, and higher cardiovascular risk. This review summarizes current evidence and underscores the potential of eGC shedding markers, especially syndecan 1 (SDC-1) and hyaluronic acid (HA), as early predictors of vascular risk and disease progression in hypertension and CKD. Full article

Background and Objectives: Cardiovascular disease is the leading cause of mortality after kidney transplantation. “Cardio-ankle vascular index” (CAVI), a recently devised technique whose utility for evaluation of cardiac risk in kidney transplantation is not well known. We investigated the associations of CAVI with echocardiographic assessment of cardiac functions and atherosclerotic parameters including FGF-23 and klotho. Materials and Methods: Two age- and gender-matched groups were subjects in the study. Group 1 included 75 KT patients with kidney transplant durations of at least 2 years; group 2 included 55 non-uremic controls. All participants underwent CAVI measurement and echocardiographic assessment. Atherosclerosis-associated parameters were determined using standard methods. Results: CAVI levels were similar between transplant patients and controls (7.26 ± 1.68 vs. 7.02 ± 1.3 m/sec); however, the percentage of subjects with pathological CAVI score (>8) was higher in transplant group (p = 0.077). Echocardiographic parameters displayed a significant increase in KT patients with higher CAVI scores. Low klotho levels were found to be significantly correlated to increased CAVI scores. Independent predictors of CAVI levels, as revealed by stepwise regression analysis, included high E/e’ (p = 0.012) and low klotho (p = 0.001). Conclusions: Our findings showed that higher CAVI scores still persist to some extent even after successful kidney transplantation and are independently linked to impaired E/e’ levels, which is an indicator of impaired diastolic dysfunction and low klotho levels. These findings underscore the importance of cardiovascular risk control in KT patients and suggest a possible role for klotho-mediated mechanisms in the development of arterial stiffness. Full article

Introduction: Metabolic acidosis is common after kidney transplantation and is associated with adverse outcomes. However, its vascular and functional correlates in kidney transplant recipients remain insufficiently characterized. Methods: We conducted a cross-sectional study of adult kidney transplant recipients attending routine outpatient visits at a tertiary transplant center. Metabolic acidosis was defined as serum bicarbonate < 22 mmol/L. Arterial stiffness was assessed by carotid–femoral pulse wave velocity (PWV), and physical frailty was evaluated using the Fried frailty phenotype. Multivariable regression models were used to identify determinants of metabolic acidosis and to examine its association with arterial stiffness and frailty severity. Results: Among 239 patients (median age 46 years), 154 (64%) had metabolic acidosis. Lower estimated glomerular filtration rate and higher systemic inflammation were independently associated with metabolic acidosis. Metabolic acidosis was independently associated with higher arterial stiffness, with a 1.41 m/s higher PWV after adjustment for age, sex, blood pressure, kidney function, and diabetes mellitus (p < 0.001). Although metabolic acidosis was associated with greater frailty severity in minimally adjusted models, this association was attenuated and no longer statistically significant after further adjustment for kidney function, diabetes, and inflammation. In stable kidney transplant recipients, metabolic acidosis is independently associated with increased arterial stiffness but not with frailty after accounting for key clinical confounders. Conclusions: These findings highlight metabolic acidosis as a marker of vascular vulnerability and a potential therapeutic target after kidney transplantation. Full article

Hypertension has traditionally been viewed as a hemodynamic disorder leading to cardiac and renal injury; however, growing evidence suggests that, in many individuals, elevated blood pressure is instead the earliest clinical expression of subtle cardiorenal dysfunction. Early abnormalities—such as low-grade albuminuria, increased renal resistive index, arterial stiffness, and masked or nocturnal hypertension—can appear before estimated glomerular filtration rate decline or elevated office blood pressure, indicating early impairment of pressure–natriuresis, heightened tissue renin–angiotensin–aldosterone system (RAAS) activity, and increased renal microvascular impedance. The aim of this review is to summarize mechanistic, clinical, and phenotypic evidence supporting the concept that hypertension functions as an early biomarker along the cardiorenal continuum. Incorporating vascular and renal biomarkers, ambulatory blood pressure phenotyping, and targeted laboratory indices into routine assessment may identify individuals transitioning from functional disturbances to structural organ damage. These abnormalities reflect a mechanistic triad of arterial stiffening, salt-sensitive RAAS activation, and circadian blood pressure disruption, collectively defining the early cardiorenal–hypertensive phenotype. Viewing hypertension through a cardiorenal lens underscores a critical opportunity for earlier detection and mechanism-oriented intervention, which may modify disease trajectory and prevent progression to overt chronic kidney disease and heart failure. Full article

Background/Objectives: Early identification of vasculitic acute kidney injury (AKI) is crucial for timely immunosuppression and improved renal outcomes; however, noninvasive adjunctive diagnostic tools remain limited. Renal elastography, a noninvasive technique that quantifies renal cortical stiffness, has been primarily investigated in chronic kidney disease, whereas evidence in acute kidney injury is scarce. This study aimed to evaluate the diagnostic utility of renal shear wave elastography for differentiating vasculitic from non-vasculitic AKI and to explore the association between baseline renal cortical stiffness and vasculitic renal outcomes. Materials and Methods: This prospective observational study included three groups: vasculitic AKI, non-vasculitic AKI, and healthy controls. Renal cortical stiffness was measured at admission using two-dimensional shear-wave elastography (2D-SWE) by radiologists blinded to clinical information. After clinicopathological confirmation of definitive diagnoses, between-group comparisons were performed and the diagnostic performance of elastography was evaluated. Additionally, in a biopsy-confirmed immunoglobulin A vasculitis nephritis (IgAVN) cohort (n = 12), baseline elastography measurements were examined in relation to one-year renal outcomes to explore potential prognostic associations. Results: The vasculitic AKI group exhibited significantly higher mean renal cortical stiffness values (9.5 ± 1.9 kPa) compared with both healthy controls (5.53 ± 0.92 kPa) and the non-vasculitic AKI group (6.61 ± 1.89 kPa) (both p < 0.01). Mean renal cortical stiffness demonstrated good diagnostic performance for distinguishing vasculitic from non-vasculitic AKI (AUC 0.86, 95% CI 0.73–0.97), with an optimal threshold of 6.79 kPa yielding 91% sensitivity and 72% specificity. In the prospective one-year follow-up of the IgAVN subcohort (n = 12), patients with unfavorable renal outcomes tended to have higher baseline renal cortical stiffness compared with those with favorable outcomes [median (min–max), 11.2 (10.8–13.3) vs. 9.1 (5.6–11.2), p = 0.046]. Conclusions: These findings suggest that renal elastography may aid in distinguishing vasculitic from non-vasculitic acute kidney injury and may provide exploratory information on the relationship between baseline cortical stiffness and renal outcomes in IgAVN. Full article

Background: Heart failure (HF) is a systemic syndrome characterized by venous congestion, which critically involves the splanchnic circulation. Conventional assessment methods often lack sensitivity for early or regional congestion. Methods: We conducted a systematic review of studies utilizing contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) to evaluate congestion in adult HF patients, synthesizing evidence up to July 2025. Results: The integrated evidence demonstrates that CEUS and SWE provide distinct, complementary quantitative data. CEUS acts as a functional pillar, detecting microvascular congestion through parameters like prolonged hepatic vein transit time. SWE serves as a structural pillar, quantifying tissue stiffness that correlates with central venous pressure, tracks decongestion, and independently predicts adverse outcomes. Together, they differentiate reversible hemodynamic congestion from irreversible fibrotic remodeling across the liver, spleen, kidneys, and heart. Conclusions: Integrating CEUS and SWE into a multi-parametric ultrasound framework provides a comprehensive, bedside assessment of systemic congestion in HF. This approach enhances early detection, improves risk stratification, and offers a potential tool for guiding and monitoring personalized decongestive therapy, representing a significant advancement in holistic HF management. Full article

Hypertension has been traditionally known to be highlighted by mean blood pressure; however, emerging evidence exhibits that blood pressure variability (BPV), including short-term, day-to-day, and visit-to-visit fluctuations can have an implication across multiple body systems. Elevated BPV reflects repetitive hemodynamic stress, affecting the physiologic hemostasis contributing to vascular injury and end organ damage. This narrative review is a compilation of recent evidence on the prognostic value of BPV, explained by pathophysiology, various devices with its measurement approaches, and, essentially, the clinical implication of BPV and the use of such devices utilizing artificial intelligence. A comprehensive literature search across PubMed, Cochrane Library, Scopus, and Web of Science were conducted, focusing on observational studies, cohorts, randomized trials, and meta-analyses. Higher BPV has been associated with an increased risk of cardiovascular mortality, stroke, coronary events, and heart failure, the progression of chronic kidney disease, cognitive decline, and preeclampsia, among other end organ damage, despite mean blood pressure. The various pathophysiologic mechanisms include autonomic dysregulation, arterial stiffness, endothelial dysfunction, circadian rhythm alteration, and systemic inflammation, which result in vascular remodeling and multisystem damage. Antihypertensive medications such as calcium channel blockers and renin–angiotensin–aldosterone system inhibitors seem to reduce BPV; randomized trials have not specifically investigated their BPV-reducing effects. The aim of this review is to highlight that BPV is a dynamic marker of multisystem risk, and question how various AI-based devices can aid continuous BPV monitoring and patient specific risk stratification. Full article

High Mobility Group Box 1 (HMGB1) and S100 proteins are major ligands of Receptor for Advanced Glycation End-products (RAGE) and have causal roles in endometriosis lesions. Yet the AGE–RAGE pathway that unifies Advanced Glycation End-products (AGEs) with these ligands has not been assessed in endometriosis. In diabetes, atherosclerosis, and chronic kidney disease, AGE–RAGE links insulin resistance and oxidative stress to inflammation, fibrosis, and organ harm. Endometriosis shares key drivers of AGE accumulation, including insulin resistance, oxidative stress, and chronic inflammation. Endometriosis is also linked to higher vascular risk and arterial stiffness. We asked whether AGE–RAGE could bridge metabolic stress to pelvic lesions and systemic risk. We did a focused review of mechanisms and an evidence map of studies on AGEs, RAGE, or known RAGE ligands in endometriosis. We grouped findings as most consistent with a driver, amplifier, consequence, or parallel role. We included 29 studies across human samples, cell systems, and animal models. Few studies measured AGE adducts directly. Most work tracked RAGE ligands (mainly HMGB1 and S100 proteins) and downstream immune and angiogenic programs. Across models, this pattern fits best with a self-reinforcing loop after lesions form. RAGE expression often aligned with lesion remodeling, especially fibrosis. Blood and skin readouts of AGE burden were mixed and varied by cohort and sample type. A central gap is receptor proof. Many models point to shared Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signaling, but few test RAGE dependence. Overall, current evidence supports AGE–RAGE as a disease-amplifying loop involved in chronic inflammation and fibrosis rather than an initiating trigger. Its effects likely vary by stage and site. Priorities now include direct lesion AGE measurement, paired systemic–pelvic sampling over time, receptor-level studies, and trials testing diet or drug interventions against clear endpoints. Outcomes could include fibrosis, angiogenesis, immune state, pain, and oocyte and follicle function. Full article

Although kidney transplantation (KT) restores renal function, residual uremic toxins, such as indoxyl sulfate (IS), may persist and contribute to vascular remodeling and aging. Aortic stiffness, reflected by carotid–femoral pulse wave velocity (cfPWV), is a strong predictor of cardiovascular events. This study enrolled KT recipients to examine the association of circulating IS with aortic stiffness. Using the SphygmoCor system, we assessed aortic stiffness, which was defined as cfPWV > 10 m/s. Serum IS concentrations were measured by liquid chromatography–tandem mass spectrometry. Of 94 KT recipients, 26 (27.7%) met the criteria for aortic stiffness. Compared with patients without aortic stiffness, those with aortic stiffness were older (p = 0.017) and had significantly higher systolic blood pressure (p = 0.011) and fasting glucose levels (p = 0.002), a higher prevalence of diabetes (p = 0.043), and higher IS levels (p = 0.002). According to multivariable logistic regression, serum IS remained independently associated with aortic stiffness (p = 0.017). According to stepwise linear regression, log-transformed IS further showed a positive correlation with cfPWV (p = 0.016). Serum IS remained an independent determinant of aortic stiffness in KT recipients, highlighting the burden of residual uremic toxins as a contributor to post-transplant vascular aging. Full article

Background and Objectives: The combination of resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) accelerates the development of chronic kidney disease (CKD), which may be largely associated with sympathetic hyperactivity. Distal renal denervation (dRDN) effectively reduces sympathetic flow to the kidneys, causing renal vasodilation and increased renal perfusion. However, this effect may be limited by nephrotoxicity due to the multiple increase in the number of contrast injections, as well as a significant blood pressure (BP) reduction, which naturally worsens renal perfusion. This study aimed to test the hypothesis that dRDN prevents the progressive decline in kidney function in patients with RHTN and T2DM. Materials and Methods: The prospective interventional study (REFRAIN, NCT04948918) included men and women > 20 y.o. with true RHTN. Eligible patients underwent dRDN. The primary endpoint was a change in eGFR from baseline to 12 months. Secondary endpoints were changes in 24 h BP, serum lipocalin-2, cystatin C, 24 h urinary albumin excretion, renal blood flow, and kidney volumes (by MRI). Multiple regression analysis was used to find independent predictors of individual estimated glomerular filtration rate (eGFR) change. Results: A total of 29 patients with RHTN and T2DM were included in the study (61.6 ± 7.2 y.o., 10 males, mean 24 h ambulatory BP: 158.1 ± 21.4/81.8 ± 12.4 mmHg (systolic/diastolic, respectively)), HbA1c: 7.8 ± 1.4%, and eGFR 56.7 ± 19.9 mL/min/1.73 m², 23 (79%) patients with CKD, and 2 patients with albuminuria only. There were no perioperative complications. Twenty-seven (93%) participants completed 12 month follow-up. eGFR did not change from baseline: +1.3 mL/min/1.73 m² [95% CI: −9.6, 12.1], despite the expected decrease due to a significant decrease in 24 h systolic BP (−18.2 mmHg [95% CI: −28.6, −7.8]). No changes in other secondary endpoints were observed. Independent predictors of individual eGFR change were baseline 24 h pulse pressure (p = 0.030) and HbA1c (p = 0.010). Conclusions: Distal RDN demonstrates a substantial nephroprotective effect in patients with RHTN and T2DM, which may be partly mediated by a reduction in arterial stiffness and is negatively dependent on baseline hyperglycemia. Full article

This work characterizes hybrid hydrogels prepared via the combination of natural and synthetic polymers. By incorporating a biocompatible compound, poly(ethylene glycol) diacrylate (PEGDA, M_n = 400), into alginate and carboxymethyl cellulose (CMC)-based hydrogels, the in situ UV crosslinking of these materials was assessed. A custom direct-write (DW) 3D bioprinter was utilized to prepare hybrid hydrogel constructs and scaffolds. A control sample, which consisted of 4% w/v alginate and 4% w/v CMC, was prepared and evaluated in addition to three PEGDA (4.5, 6.5, and 10% w/v)-containing hybrid hydrogels. Rotational rheology was utilized to evaluate the thixotropic behavior of these materials. Filament fusion tests were employed to generate bilayer constructs of various pore sizes, providing metrics for the printability and diffusion rate of hydrogels post-extrusion. Printability indicates the shape fidelity of pore geometry, whereas diffusion rate represents material spreading after deposition. Curing kinetics of PEGDA-containing hydrogels were evaluated using photo-Differential Scanning Calorimetry (DSC) and photorheology. The Kamal model was fitted to photo-DSC results, enabling an assessment and comparison of the curing kinetics for PEGDA-containing hydrogels. Photorheological results highlight the increase in hydrogel stiffness concomitant with PEGDA content. The range of obtained complex moduli (G*) provides utility for the development of brain, kidney, and heart tissue (620–4600 Pa). The in situ UV irradiation of PEGDA-containing hydrogels improved the shape fidelity of printed bilayers and decreased filament diffusion rates. In situ UV irradiation enabled 10-layer scaffolds with 1 × 1 mm pore sizes to be printed. Ultimately, this study highlights the utility of PEGDA-containing hybrid hydrogels for high-resolution DW 3D bioprinting and potential application toward customizable tissue analogs. Full article

Phosphate is emerging as an active mediator of oxidative stress and vascular injury in chronic kidney disease (CKD). This emerging pathophysiological framework, referred to as “Phosphatopathy”, describes the systemic syndrome driven by chronic phosphate overload and characterized by oxidative stress, inflammation, endothelial dysfunction, vascular calcification, cellular senescence, and metabolic imbalance. Beyond being a biochemical marker, phosphate overload triggers NOX-derived reactive oxygen species (ROS), activates Wnt/β-catenin and TGF-β signaling, and disrupts the FGF23–Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition–inflammation–atherosclerosis (MIA) syndrome. Experimental and clinical data reveal that the phosphate/urinary urea nitrogen (P/UUN) ratio is a sensitive biomarker of inorganic phosphate load, while emerging regulators such as microRNA-125b and calciprotein particles integrate phosphate-driven oxidative and inflammatory responses. Therapeutic strategies targeting phosphate burden—rather than serum phosphate alone—include dietary restriction of inorganic phosphate, non-calcium binders, magnesium and zinc supplementation, and activation of important pathways related to the activation of antioxidant defense such as AMP-activated protein kinase (AMPK) and SIRT1. This integrative framework redefines phosphate as a modifiable upstream trigger of oxidative and metabolic stress in CKD. Controlling phosphate load and redox imbalance emerges as a convergent strategy to prevent vascular calcification, improve arterial stiffness, and reduce cardiovascular risk through personalized, mechanism-based interventions. Full article