Search Results (58)

Background: Chronic kidney disease (CKD) is an established global health problem, with the increased prevalence of vascular inflammation, accelerated atherogenesis, and thrombotic risk all contributing to overall cardiovascular risk. The major CKD-specific risk factor is presumed to be the accumulation of uremic toxins in circulation and tissues, further accelerating the progression of CKD and its co-morbidities, including those of bone mineral disorders and cardiovascular diseases. Materials and Methods: In our narrative review, we focused on non-traditional cardiovascular risk factors, as they evolve with declined kidney function and are potentially further modulated by the choice of kidney replacement therapy. Results: Based on the data from the literature to date, the pre-eminent role of non-traditional risk factors emerges to mediate inflammation and increased cardiovascular mortality. In particular, patients receiving hemodialysis (HD) display dramatically increased CVD-mediated mortality. This intensified state of inflammation may be linked to the direct exposure of the bloodstream to a bio-incompatible environment in HD; for both complement-mediated and non-complement-mediated reactions, the possible contribution of neutrophil extracellular traps and complement activation-related pseudoallergy are reviewed in detail. Conclusions: Our narrative review emphasizes key elements of a bio-incompatible HD environment that may contribute to increased cardiovascular mortality in patients receiving HD. Summarizing these results may provide conceptual opportunities to develop new therapeutic targets. Full article

Background: Calmodulin is a calcium-signaling protein implicated in cardiac remodeling and could be released extracellularly. It was previously identified as differentially expressed in hypertensive pediatric chronic kidney disease (CKD). This study assessed plasma calmodulin as a cardiovascular disease (CVD) biomarker in pediatric CKD and compared it with traditional risk markers. Methods: We conducted a cross-sectional study of 81 children with CKD aged 3–18 years. All underwent clinical assessments and echocardiography; 44 had carotid ultrasound, and 38 completed ambulatory blood pressure monitoring (ABPM). Results: Most participants had preserved renal function (median eGFR, 104.4 mL/min/1.73 m²). Plasma calmodulin levels were significantly associated with early markers of CVD, including interventricular septal thickness, left ventricular mass, carotid intima–media thickness, and ABPM systolic measures (all r > 0.2; p < 0.05). In multivariable analysis, only calmodulin and office systolic blood pressure (BP) independently predicted abnormal BP profiles. Conclusions: Plasma calmodulin may serve as a sensitive, though non-specific, early CVD biomarker in pediatric CKD and could complement conventional screening tools. Full article

Non-traditional cardiovascular risk factors (RFs) are increasingly emerging as important modifiers of cardiovascular risk (CVR), offering insights beyond traditional metrics like hypertension, diabetes, and dyslipidemia. These include novel biomarkers, chronic conditions (e.g., chronic kidney disease and chronic obstructive pulmonary disease), environmental exposures, chronic inflammation, infections, psychosocial factors, and sex-specific conditions, all of which influence the prediction, management, and outcomes of cardiovascular disease (CVD). These additional RFs may impact on CVD prediction and add valid information during tailored patient assessment and management. Therefore, a careful assessment of both traditional and non-traditional cardiovascular RFs, with a personalized treatment, could dramatically reduce the total CVD burden. Nevertheless, further research is needed to precisely estimate the magnitude of their impact as risk and prognosis modifiers in order to be included in future risk charts. This review provides a critical analysis of non-traditional RFs, their pathophysiological mechanisms, and their implications for personalized care. Integrating these factors into CVR assessment can reclassify patient risk categories, optimize therapeutic strategies, and improve prognosis. However, further research is needed to refine their inclusion in risk charts and evaluate their impact on public health outcomes. A tailored, multidisciplinary approach is essential to reduce the burden of CVD and associated mortality. Full article

Background: The early stages of chronic kidney disease (CKD) are often undetectable on traditional non-contrast computed tomography (NCCT) images through visual assessment by radiologists. This study aims to evaluate the potential of radiomics-based quantitative features extracted from NCCT, combined with machine learning techniques, in differentiating CKD stages 1–3 from healthy controls. Methods: This retrospective study involved 1099 CKD patients (stages 1–3) and 1099 healthy participants who underwent NCCT. Bilateral kidney volumes of interest were automatically segmented using a deep learning-based segmentation approach (VB-net) on CT images. Radiomics models were constructed using the mean values of features extracted from both kidneys. Key features were selected through Relief, MRMR, and LASSO regression algorithms. A machine learning classifier was trained to differentiate CKD from healthy kidneys and compared with the radiologist assessments. Model performance was evaluated using the area under the curve (AUC) of receiver operating characteristic analysis. Results: In the training set, the AUCs for the Gaussian process (GP) classifier model and radiologist assessments were 0.849 and 0.570, respectively. In the testing set, the AUC values were 0.790 for the GP model and 0.575 for radiologist assessments. Conclusions: The NCCT-based radiomics model demonstrates significant clinical utility by enabling non-invasive, early diagnosis of CKD stages 1–3, outperforming radiologist assessments. Full article

Background/Objectives: Fecal calprotectin (FC) is a biomarker of intestinal inflammation widely used in the assessment of gastrointestinal disorders. However, its role in chronic kidney disease (CKD) remains unclear. Given the growing recognition of the gut–kidney axis in CKD pathophysiology, this study aimed to investigate the association between FC levels, systemic inflammation, renal outcomes, and mortality in CKD patients. Methods: We enrolled a total of 515 CKD patients who underwent fecal calprotectin measurement between 2016 and 2023. After applying the exclusion criteria (inflammatory bowel disease, ongoing renal replacement therapy, or incomplete laboratory data), 260 patients were included in the final analysis and stratified into low-FC (<102 μg/g, n = 130) and high-FC (≥102 μg/g, n = 130) groups based on the median FC value. Factors associated with kidney disease progression and patient survival were analyzed. Results: Patients in the high-FC group (≥102 μg/g) were significantly older (72.8 ± 14.63 vs. 64.02 ± 18.15 years, p < 0.0001) and had a higher prevalence of diabetes mellitus (55.38% vs. 42.31%, p = 0.0349), heart failure (21.54% vs. 7.69%, p = 0.0016), and history of acute kidney injury (33.85% vs. 18.46%, p = 0.0048). Elevated FC was independently associated with increased mortality risk (hazards ratio [HR] 1.658, 95% confidence interval [CI] 1.034–2.658, p = 0.0357) with higher mortality rates (48.36 vs. 18.46 per 100,000 person-years). Subgroup analyses revealed stronger associations between FC and mortality in males (HR 2.160, 95% CI 1.046–4.463, p = 0.0375), elderly patients (≥75 years) (HR 2.122, 95% CI 1.209–3.725, p = 0.0088), and non-diabetic patients (HR 2.487, 95% CI 1.141–5.421, p = 0.0219). While FC was not significantly associated with end-stage kidney disease (ESKD) progression (odds ratio [OR] 1.289, 95% CI 0.455–3.650, p = 0.6323), higher FC levels paradoxically predicted slower estimated glomerular filtration rate (eGFR) decline (OR 2.763, 95% CI 1.139–6.699, p = 0.0245). Combined analysis revealed patients with both elevated FC and high-sensitivity C-reactive protein (hs-CRP) had the highest mortality risk (HR 3.504, 95% CI 1.163–10.554, p < 0.0001) compared to those with low levels of both markers. Conclusions: FC is a potential prognostic biomarker for mortality in CKD patients, independently of traditional inflammatory markers. Further research is warranted to elucidate the mechanisms underlying its paradoxical relationship with renal outcomes and its potential role in risk stratification and therapeutic targeting in CKD. Full article

Background/Objectives: Cardiovascular disease is the main cause of morbidity and mortality in Chronic Kidney Disease (CKD), so it is of great importance to find simple and non-invasive tools to detect vascular damage in pre-dialysis CKD patients. This study aimed to assess the applicability of non-invasive techniques to evaluate vascular damage in stages CKD-2 to CKD-5 and its progression after an 18-month follow-up using (A) carotid–femoral pulse wave velocity (PWV) to assess aortic stiffness and (B) Superb Microvascular Imaging (SMI) ultrasound to assess adventitial neovascularization compared with other traditional techniques to evaluate vascular damage, such as carotid intima–media thickness and Kauppila index. Methods: The study involved 43 CKD patients in stages CKD-2 to CKD-5 and a group of 38 sex- and age-matched controls, studied at baseline and at an 18-month follow-up. Age, sex, body mass index, arterial pressure, pharmacological treatments, and blood and urinary parameters were collected. Aortic stiffness was determined by carotid–femoral PWV and abdominal aortic calcification was assessed in lateral lumbar X-rays and quantified by the Kauppila index. Carotid intima–media thickness (cIMT), the number of carotid plaques, and adventitial neovascularization were evaluated by SMI. Results: Vascular impairment was mostly detected in CKD-4 and CKD-5 stages, with increased aortic stiffness measured by PWV and increased carotid plaques and adventitial neovascularization measured by SMI ultrasound. Furthermore, CKD-5 patients showed greater abdominal aortic calcification. Interestingly, CKD patients displayed a negative correlation between serum soluble Klotho (sKlotho) and cIMT. Finally, CKD patients showed no progression of vascular impairment after the 18-month follow-up, with the exception of carotid plaques. Conclusions: Performing non-invasive PWV and SMI ultrasound might be useful to evaluate vascular damage in CKD before entering dialysis, possibly helping to prevent cardiovascular events, although future studies should clarify the use of these techniques in clinical practice. Full article

Chronic kidney disease (CKD) is a global health crisis affecting over 10% of the population, with mortality rates increasing significantly. Current management strategies, including expensive medications and renal replacement therapies, highlight the need for cost-effective, conservative approaches. This review examines the evidence for plant-dominant low-protein diets (PLADO) in managing non-dialysis-dependent CKD. Existing guidelines for protein restriction in CKD vary considerably, with inconsistencies and a lack of personalization noted in the KDOQI and KDIGO recommendations. While traditional low-protein diet trials show limited success due to poor adherence and marginal benefits, PLADO offers a potentially more sustainable alternative. PLADO’s advantages include improved nutrient density, reduced dietary acid load, anti-inflammatory effects, and beneficial modulation of the gut microbiome, potentially reducing uremic toxins and improving cardiovascular health. However, challenges remain, including adherence issues, potential nutrient deficiencies, and potassium management. Although observational studies show promise, further large-scale randomized controlled trials are necessary to validate PLADO’s efficacy and establish optimal dietary composition. A personalized, multidisciplinary approach is essential for successful implementation and monitoring to maximize PLADO’s benefits in improving outcomes for individuals with NDD-CKD. Full article

The El Valle Volcanic Complex, located in the province of Cocle, Panama, presents geological characteristics that could be linked to public health problems. This study focuses on the municipalities of San Juan de Dios, Pajonal, and Caballero, where water is consumed directly from springs (groundwater outcrops). The region has a high incidence of non-traditional chronic kidney disease (nt-CKD) that may be associated with the natural presence of potentially toxic elements (PTEs) in the water. This study aimed to analyze the concentration of PTEs in groundwater and assess the carcinogenic (CR) and non-carcinogenic (HQ) risk to human health from the direct ingestion of water. Sediments, rocks, and water samples were collected. Major ions and PTEs (As, Al, Ba, Co, Cu, Fe, Mn, Sr, Sb, Pb, V, and Zn) were measured, and the mineralogical composition of the rocks was analyzed. The results showed that Fe was the only PTE that exceeded the recommended concentration for drinking water, according to Panama regulations, and Pb according to USEPA. In Caballero and Pajonal, the acceptable threshold for CR and HQ was exceeded, a higher percentage than in San Juan de Dios. The PTEs that contribute most to the risk are Co, Cu, Pb, and As. This study suggests that the region’s historical volcanic activity, involving the release of minerals rich in these PTEs, along with the interaction between groundwater and volcanic rocks, may be contributing to the presence of PTEs in the water. This geological phenomenon could be what has led to prolonged exposure to these elements, which correlates with the high prevalence of chronic kidney disease in the area. This is a novel study, the first conducted in Panama, as it seeks to uncover the relationship between the geology of the site, the presence of PTEs in the groundwater of springs for human consumption, and the implication of health risks, with the aim of generating new information for decision makers for the generation of public policies on health issues such as nt-CKD and cancer in the region. Full article

Objectives: This study aimed to investigate the relationship between the sarcopenia index (SI), which is derived from serum creatinine and cystatin C levels, and osteoporosis in chronic kidney disease (CKD). Methods: This study initially included patients who underwent dual-energy X-ray absorptiometry (DXA) and serum creatinine and cystatin C testing between 2005 and 2022. Subsequently, patients diagnosed with CKD were selected for the final analysis, totaling 102 patients. Both traditional and new SI were calculated, with each participant categorized into one of two groups (non-osteoporosis and osteoporosis) according to bone mineral density. To enhance statistical validity, the patients were further divided into low- and high-index groups based on the median value of both indices for comparative analysis. The association between SI and the risk of osteoporosis was estimated using multivariable logistic regression analysis. Results: Participants with lower SI values had lower bone mineral density and a higher diabetes mellitus prevalence. The non-osteoporotic group exhibited significantly higher mean values for both traditional and new SI. Multivariable logistic regression analysis identified three statistically significant variables: both indices, sex, and diabetes mellitus. Both traditional and new SI yielded individual odds ratios of 0.906 with estimated areas under the curve of 0.847 for traditional SI and 0.833 for new SI. Conclusions: This study confirmed that both traditional and new SI are associated with osteoporosis in patients with CKD. Therefore, clinicians can raise the suspicion of osteoporosis based on traditional and new SI in patients with CKD, even when DXA results are unavailable. Full article

Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease. However, VC may occur earlier and faster in these patients if it is associated with new or non-traditional risk factors such as oxidative stress, anemia, and inflammation. In chronic kidney disease, several pathophysiological processes contribute to vascular calcifications, including osteochondrogenic differentiation of vascular cells, hyperphosphatemia and hypercalcemia, and the loss of specific vascular calcification inhibitors including pyrophosphate, fetuin-A, osteoprotegerin, and matrix GLA protein. In this review we discuss the main traditional and non-traditional risk factors that can promote VC in patients with kidney disease. In addition, we provide an overview of the main pathogenetic mechanisms responsible for VC that may be crucial to identify new prevention strategies and possible new therapeutic approaches to reduce cardiovascular risk in patients with kidney disease. Full article

The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodium–glucose cotransporter 2 inhibitors, initially used for glycemic control, now recognized for their renoprotective properties in both diabetic and non-diabetic populations. Another drug, Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has emerged as a promising agent, offering anti-inflammatory and antifibrotic benefits with fewer side effects than traditional steroidal options. Finally, dual inhibition of angiotensin II and endothelin-1 receptors through agents like Sparsentan presents a novel approach with significant antiproteinuric effects in IgA nephropathy and focal segmental glomerulosclerosis. This brief review summarizes the mechanisms by which proteinuria promotes kidney damage and the renoprotective therapeutic approaches available, which can be combined with lifestyle modifications and specific treatments for underlying diseases to mitigate the progression of chronic kidney disease. Full article

Introduction: Finerenone, a third-generation non-steroidal mineralocorticoid receptor antagonist (MRA), offers a targeted approach to managing cardiovascular outcomes, particularly in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Unlike traditional MRAs such as spironolactone and eplerenone, which can cause off-target hormonal side effects and hyperkalemia, Finerenone selectively binds to mineralocorticoid receptors, reducing these risks. Recent randomized controlled trials have demonstrated Finerenone’s potential to improve cardiovascular outcomes, making it a promising alternative in the management of heart failure and other cardiovascular conditions associated with CKD and T2D. Methods: We conducted a scoping review using PRISMA guidelines. A search for “Finerenone” in the PubMed, Embase, and Cochrane Library databases included randomized controlled trials (RCTs), post hoc analyses, and relevant meta-analyses on cardiovascular outcomes. Data were synthesized narratively, assessing study quality through strengths and limitations. Discussion: Finerenone has shown significant benefits and a superior safety profile compared with traditional MRAs like spironolactone and eplerenone in managing CKD, T2D, and heart failure. It effectively reduces cardiovascular and renal events while minimizing risks such as hyperkalemia and hormonal side effects associated with steroidal MRAs. Future studies, including the REDEFINE-HF, FINALITY-HF, and CONFIRMATION-HF trials, will further explore Finerenone’s potential across diverse heart failure phenotypes, including its role in heart failure with mildly reduced and preserved ejection fractions, potentially establishing it as a cornerstone therapy in heart failure management. Conclusions: Finerenone represents a significant advancement in MRA therapy, offering enhanced safety and efficacy in managing cardiovascular outcomes in CKD and T2D patients. The current evidence supports its use as a promising alternative to traditional MRAs, particularly in patients intolerant to steroidal MRAs. Further trials are needed to fully establish its potential across diverse patient populations, including those with varying heart failure phenotypes. Full article

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half–fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a “systemic disease” and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a “holistic” rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients. Full article

Mesoamerican nephropathy (MeN) is a non-traditional chronic kidney disease in some areas of Mesoamerica. The health risk from nephrotoxic metals, such as arsenic (As), lead (Pb), mercury (Hg), vanadium (V), cadmium (Cd), rubidium (Rb), chromium (Cr), and nickel (Ni), was assessed in drinking water and soils. These metals, even at low concentrations, have the capacity to induce epigenetic damage and a nephrotoxic effect. The quantification of metals in soils was made through X-ray fluorescence spectrometry (XRF) and inductively coupled plasma optical emission spectrophotometry (ICP-OES), while the quantification of metals in water was carried out through inductively coupled plasma mass spectrometry (ICPMS) and atomic absorption (AA) spectrometry. The levels of As, Hg, Cd, and V in water were within the permissible limits, whereas Pb was found to be double and triple the value recommended by the World Health Organization. The non-carcinogenic risk from As in soil was evaluated using the Hazard Index (HI), and the route of ingestion was found to be the most important route. The results indicate that consuming water or ingesting soil particles with Pb and As poses a health risk to humans. Therefore, these findings identify the presence of toxicants in an exposure scenario and justify further research into these metals in people and the analysis of exposure routes. Full article

Urease, a pivotal enzyme in nitrogen metabolism, plays a crucial role in various microorganisms, including the pathogenic Helicobacter pylori. Inhibiting urease activity offers a promising approach to combating infections and associated ailments, such as chronic kidney diseases and gastric cancer. However, identifying potent urease inhibitors remains challenging due to resistance issues that hinder traditional approaches. Recently, machine learning (ML)-based models have demonstrated the ability to predict the bioactivity of molecules rapidly and effectively. In this study, we present ML models designed to predict urease inhibitors by leveraging essential physicochemical properties. The methodological approach involved constructing a dataset of urease inhibitors through an extensive literature search. Subsequently, these inhibitors were characterized based on physicochemical properties calculations. An exploratory data analysis was then conducted to identify and analyze critical features. Ultimately, 252 classification models were trained, utilizing a combination of seven ML algorithms, three attribute selection methods, and six different strategies for categorizing inhibitory activity. The investigation unveiled discernible trends distinguishing urease inhibitors from non-inhibitors. This differentiation enabled the identification of essential features that are crucial for precise classification. Through a comprehensive comparison of ML algorithms, tree-based methods like random forest, decision tree, and XGBoost exhibited superior performance. Additionally, incorporating the “chemical family type” attribute significantly enhanced model accuracy. Strategies involving a gray-zone categorization demonstrated marked improvements in predictive precision. This research underscores the transformative potential of ML in predicting urease inhibitors. The meticulous methodology outlined herein offers actionable insights for developing robust predictive models within biochemical systems. Full article