Search Results (1,727)

Hypertension is highly prevalent among patients with chronic kidney disease (CKD), contributing significantly to cardiovascular morbidity and progressive renal decline. This overview explores the intricate pathophysiologic mechanisms driving hypertension in renal insufficiency, including volume overload, renin–angiotensin–aldosterone system (RAAS) activation, sympathetic overactivity, and vascular dysfunction. Diagnostic challenges such as white-coat hypertension and the underuse of ambulatory monitoring are discussed, along with the importance of volume assessment and target organ evaluation. We also emphasize individualized management strategies combining lifestyle modification, pharmacotherapy—including RAAS inhibitors, diuretics, and novel agents—and the growing role of device-based interventions. In particular, renal denervation (RDN) has emerged as a potential adjunctive option for selected patients with resistant hypertension in CKD, with preliminary evidence suggesting blood pressure reduction in selected and carefully studied populations, including dialysis-dependent patients. Special considerations for transplant recipients, elderly individuals, and those on dialysis are highlighted, underscoring the need for nuanced, patient-centered care. Misconceptions surrounding RAAS blockade, dialysis hypotension, and therapeutic inertia are critically appraised. Finally, future directions point to biomarker-driven approaches, digital health integration, and large-scale trials on RDN to refine treatment paradigms. This comprehensive synthesis offers a pragmatic framework for clinicians managing hypertension in CKD, aligning mechanistic insights with emerging evidence and clinical realities. Full article

Background: The Lung Immune Prognostic Index (LIPI) has recently emerged as a novel prognostic biomarker in several malignancies, particularly in patients receiving immunotherapy. However, its role in renal cell carcinoma (RCC), especially in non-metastatic and tyrosine kinase inhibitor (TKI)-treated patients, remains unclear. Methods: In this retrospective cohort study, 153 patients diagnosed with RCC between 2012 and 2024 were analyzed. Prognostic scores including LIPI, International Metastatic RCC Database Consortium (IMDC), and Memorial Sloan Kettering Cancer Center (MSKCC) scores were calculated. The patients were stratified into risk groups (good, intermediate, and poor) based on these scores. Survival analyses were performed using Kaplan–Meier and Cox regression methods. Correlations between scoring systems were assessed using Pearson’s correlation. Results: The median follow-up was 29.1 months. A total of 55 (35.9%) patients had metastases at diagnosis. LIPI was significantly associated with overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) (p < 0.05). In the multivariate Cox analysis, LIPI remained an independent prognostic factor for OS and PFS. Strong positive correlations were found between LIPI and both IMDC and MSKCC scores (r > 0.6, p < 0.001). Notably, LIPI demonstrated prognostic relevance even in patients treated with TKIs. Conclusions: LIPI is a simple and accessible prognostic tool that provides significant survival stratification in RCC patients. Its predictive utility extends beyond immunotherapy cohorts, indicating potential value in broader RCC management. Integration of LIPI into current prognostic models may improve individualized treatment approaches. Full article

Background/Objectives: End-stage renal disease (ESRD) is characterized by profound and progressive microvascular dysfunction that contributes significantly to systemic morbidity. Because the retinal and renal microcirculations share structural and physiological similarities, optical coherence tomography (OCT) and OCT angiography (OCTA) have emerged as promising tools for detecting ocular microvascular changes that may parallel systemic vascular injury. This systematic review aimed to consolidate evidence on chronic retinal and choroidal alterations in ESRD as assessed by OCT and OCTA. Methods: A systematic search of PubMed/MEDLINE (inception–June 2025) was performed using combinations of terms related to OCT, OCTA, ESRD, and hemodialysis. After removing duplicates and screening titles, abstracts, and full texts, we included clinical studies involving adults with ESRD or undergoing dialysis that reported chronic or baseline OCT/OCTA findings. Non-English publications, editorials, conference abstracts, case reports, and studies limited to acute pre-/post-dialysis changes were excluded. Seventeen studies met eligibility criteria. Acute findings were summarized narratively only when no chronic data existed for a specific parameter but were not incorporated into the primary synthesis. Results: Across eligible studies, chronic structural and perfusion abnormalities were consistently reported, including thinning of the retinal nerve fiber and ganglion cell layers, reduced macular and peripapillary vascular densities, enlarged foveal avascular zones, and decreased choroidal thickness. These alterations aligned with markers of disease severity and systemic microvascular burden. Conclusions: Retinal imaging reveals reproducible chronic microvascular changes in ESRD and may serve as an accessible adjunct for systemic vascular assessment. We highlight the potential significance of retinal vascular screening in this population and the need for more standardized imaging protocols to support the effective integration of retinal biomarkers into CKD diagnostic and monitoring strategies. Full article

Introduction: Diabetes mellitus (DM) is a prevalent metabolic disorder frequently leading to serious renal complications, particularly diabetic nephropathy. This retrospective case–control study investigated the levels and associations of commonly used enzymatic (serum creatinine and urea) and physiological (glomerular filtration rate [GFR]) markers of kidney function in diabetic patients compared to non-diabetic controls. Methodology: A total of 237 participants were enrolled, comprising 81 diabetic cases and 156 non-diabetic controls. Creatinine and urea levels were determined using enzymatic methods, measuring optical density, whereas GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, based on creatinine, age, and sex. Statistical comparisons include p-value, Pearson correlation, etc. Results: The diabetic group exhibited significantly higher mean levels of serum creatinine (2.08 ± 2.26 mg/dL) and urea (57.71 ± 38.75 mg/dL) and a significantly lower mean GFR (59.59 ± 34.16 mL/min/1.73 m²) compared to the non-diabetic control group (0.95 ± 0.69 mg/dL, 31.79 ± 20.49 mg/dL, and 96.72 ± 23.77 mL/min/1.73 m², respectively; all comparisons with p < 0.005). Correlation analysis revealed a more scattered positive association between creatinine and urea, and a pronounced inverse correlation between GFR and both creatinine and urea in the diabetic cases, suggesting a compromised renal function profile. Conclusions: Our findings demonstrate a significant association between diabetes and impaired renal function, as evidenced by elevated creatinine and urea levels and reduced GFR. These readily available biomarkers are crucial prognostic indicators for the early detection and effective management of diabetic nephropathy, emphasizing the importance of rigorous metabolic and blood pressure control to mitigate disease progression. Full article

Diabetic ketoacidosis (DKA) remains a life-threatening complication of diabetes mellitus with suboptimal outcomes despite standard management. Emerging evidence suggests that thiamine (vitamin B1) deficiency may play an under-recognized role in DKA pathophysiology and clinical course. This narrative review synthesizes current evidence regarding thiamine deficiency in diabetes and DKA, examining molecular mechanisms, clinical implications, and the rationale for thiamine supplementation as adjunctive therapy. Thiamine deficiency is highly prevalent in diabetes, with plasma concentrations reduced by approximately 75% compared to healthy controls. In DKA specifically, 25–35% of patients present with thiamine deficiency, which often worsens during insulin therapy. The primary mechanism involves hyperglycemia-induced downregulation of renal thiamine transporters (THTR-1 and THTR-2), resulting in 16–24-fold increased renal clearance and massive urinary losses. Thiamine pyrophosphate serves as an essential cofactor for three critical enzymes in glucose metabolism: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Deficiency impairs these pathways, causing pyruvate accumulation with conversion to lactate (resulting in lactic acidosis), compromised TCA cycle function (reducing ATP production by 40–48%), and decreased NADPH generation (increasing oxidative stress). Clinical manifestations include persistent metabolic acidosis despite standard therapy, myocardial dysfunction with elevated cardiac biomarkers, neurological impairment, and prolonged recovery times. Cellular studies demonstrate that thiamine supplementation significantly improves mitochondrial oxygen consumption in DKA patients. The high prevalence of thiamine deficiency in DKA, compelling biochemical rationale, excellent safety profile, and preliminary mechanistic evidence support the urgent need for large-scale randomized controlled trials examining thiamine supplementation to definitively establish efficacy, optimal dosing, and patient selection criteria. Full article

Clear-cell renal cell carcinoma (ccRCC) accounts for the majority of kidney cancer diagnoses and exhibits widely variable clinical behaviour. The dataset described here was generated to support the discovery of robust biomarkers of tumour cell-cycle arrest and to inform the risk-stratified management of ccRCC. We assembled four independent cohorts including 480 patients from the UK arm of the SORCE adjuvant trial, 300 patients from a surgically treated series in Korea, 120 patients from a retrospective Scottish cohort, and a paired primary–metastatic cohort comprising 62 patients. Formalin-fixed paraffin-embedded nephrectomy specimens were processed for routine hematoxylin and eosin (H&E) histology, and for multiplex immunofluorescence (mIF). The mIF panels detect the cyclin-dependent kinase inhibitor p21^CDKN1a, the DNA replication licencing factor MCM2, endoglin/CD105, Lamin B1 and nuclear DNA (Hoechst). Whole-slide images (WSIs) were acquired at high resolution, and artificial-intelligence pipelines were used to segment nuclei, classify individual cells into arrested phenotypes, and calculate the fraction of cells. Accompanying metadata include demographics, tumour stage, grade, Leibovich score, treatment arm (sorafenib/placebo), relapse events, and disease-free survival. All images and derived tables are released under a CC0 licence via the BioImage Archive, ensuring unrestricted reuse. This multi-cohort dataset provides a rich resource for studying cell-cycle arrest and proliferation markers, training image-analysis algorithms, and developing prognostic signatures in RCC. Full article

Background: Atrial Fibrillation (AF) is associated with a prothrombotic state and increased risk of ischemic stroke. Type 2 diabetes mellitus (T2DM) is a major cardiometabolic comorbidity in AF and independently increases thromboembolic risk. D-dimer is a well-established biomarker of coagulation activation and fibrin turnover, but the specific contribution of T2DM to D-dimer levels in AF remains insufficiently characterized in real-world cohorts. Methods: We conducted a retrospective, observational, single-center study including 300 adult patients with non-valvular AF evaluated at a tertiary university hospital. Patients were stratified according to the presence of T2DM (150 with T2DM and 150 without diabetes). Plasma D-dimer levels were compared between groups and analyzed across clinically relevant thresholds and CHA₂DS₂-VASc categories. Multivariable linear and logistic regression models were used to assess the independent association between T2DM and D-dimer levels after adjustment for demographic factors, comorbidities, renal function, prior stroke, CHA₂DS₂-VASc score components, and oral anticoagulation. Results: Patients with T2DM exhibited significantly higher D-dimer levels than non-diabetic patients (median 0.94 vs. 0.63 µg/mL FEU, p < 0.001). T2DM was independently associated with higher log-transformed D-dimer levels (adjusted β = 0.19, p < 0.001) and with increased odds of elevated D-dimer above both 0.5 µg/mL and 1.0 µg/mL thresholds. Across all CHA₂DS₂-VASc categories, patients with T2DM consistently showed higher D-dimer concentrations. Findings remained robust in sensitivity analyses restricted to anticoagulated patients. Conclusions: In patients with atrial fibrillation, type 2 diabetes mellitus is associated with increased coagulation activity as reflected by higher D-dimer levels, independent of clinical thromboembolic risk. These results support the concept of a diabetes-associated hypercoagulable AF phenotype and highlight the potential role of coagulation biomarkers in refining risk stratification. Full article

Chronic Kidney Disease (CKD) and Colorectal Cancer (CRC) share a profound epidemiological link, supported by Mendelian randomization studies suggesting causality. This review articulates a refined Gut–Kidney Axis, focusing on the pathophysiology of indole-derived uremic toxins. CKD-induced dysbiosis drives hepatic synthesis and systemic accumulation of indoxyl sulfate, which is proposed to promote carcinogenesis via Aryl Hydrocarbon Receptor (AhR) and Akt signaling, ultimately upregulating c-Myc and EGFR. We propose a two-compartment model: while systemic indoxyl sulfate reflects the total gut indole pool (mainly from planktonic bacteria), adherent bacteria like Fusobacterium nucleatum may create high-concentration indole hotspots within the tumor microenvironment. Clinically, we advocate for protein-independent DNA methylation biomarkers (SEPT9, SDC2) to avoid renal confounding. Furthermore, we propose a novel diagnostic panel integrating serum indoxyl sulfate (systemic load) and urinary indoxyl sulfate (gut production) to guide therapy. Therapeutically, targeting upstream drivers (AhR/Akt) may bypass resistance to anti-EGFR therapies in KRAS-mutated tumors. We also discuss the repurposing of the oral adsorbent AST-120 and emerging bacteriophage therapies as strategies to disrupt this oncogenic axis. This review offers a comprehensive framework for stratified management of CKD-associated CRC. Full article

Background: Early risk stratification in ST-elevation myocardial infarction (STEMI) remains critical, particularly for anticipating adverse outcomes such as the coronary no-reflow phenomenon (NRP) and early mortality. The Endothelial Activation and Stress Index (EASIX), calculated from routine laboratory parameters, has emerged as a potential biomarker reflecting systemic endothelial dysfunction. This study evaluated the prognostic value of admission EASIX for the NRP and in-hospital mortality in STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Methods: In this retrospective single-center cohort, 1931 STEMI patients treated with pPCI between January 2023 and January 2025 were included. EASIX was calculated at admission. NRP was defined as post-PCI TIMI flow ≤ 2 or TIMI 3 flow with impaired myocardial blush (TMPG ≤ 1). Multivariable logistic regression, reclassification analyses (NRI/IDI), ROC analysis, and calibration methods were used to assess predictive performance. Sensitivity and interaction analyses were conducted. Results: NRP occurred in 14.1%, and in-hospital mortality was 2.5%. EASIX was independently associated with both outcomes (NRP: adjusted OR 1.485, 95% CI 1.286–1.715; mortality: adjusted OR range 1.371–2.096 across models; all p < 0.001). EASIX significantly improved risk reclassification for both NRP and in-hospital mortality (NRI > 0.20). ROC-AUCs were 0.706 for NRP and 0.810 for mortality. Restricted cubic spline and LOWESS analyses revealed nonlinear risk escalation. Calibration plots and Brier scores confirmed model reliability. Associations persisted across ischemic time and renal function strata. Conclusions: Admission EASIX is independently associated with NRP and in-hospital mortality in STEMI. Easily accessible and integrative, EASIX may enhance early risk stratification. External validation is warranted before clinical implementation. Full article

Personalized anesthesia has emerged as a key direction in modern perioperative medicine, driven by advances in molecular biology, analytical technologies, and digital monitoring. Traditional physiological parameters often fail to detect early stages of organ dysfunction, whereas molecular biomarkers provide earlier and more sensitive insight into inflammation, oxidative stress, neurotoxicity, and renal or hepatic injury. Inflammatory markers such as IL-6, CRP, and PCT indicate early immune activation, while oxidative stress biomarkers, including 8-isoprostanes and malondialdehyde, quantify metabolic imbalance and ischemia–reperfusion injury. Neurotoxicity biomarkers such as S100β, NSE, and GFAP allow early detection of subclinical cerebral injury, whereas kynurenine-pathway metabolites reflect neuroinflammation and the risk of postoperative cognitive dysfunction. Renal biomarkers such as NGAL, KIM-1, and cystatin C detect acute kidney injury significantly earlier than creatinine, and miR-122 holds strong potential as an early marker of hepatocellular injury. Genetic and epigenetic biomarkers—including polymorphisms in CYP2D6, CYP3A4/5, RYR1, OPRM1, and COMT, as well as microRNA-based signatures—enable individualized drug dosing and optimization of anesthetic strategies. Meanwhile, digital biomarkers such as EEG-derived indices, HRV, and NIRS provide continuous real-time physiological monitoring and can integrate with AI-based algorithms for predictive, adaptive anesthesia management. Although no single biomarker meets all criteria for an ideal clinical indicator, combining molecular, genetic, and digital biomarkers represents the most promising pathway toward fully personalized, safe, and outcome-optimized perioperative care. Full article

Background/Objectives: Cancer patients are highly susceptible to infectious diseases due to malignancy- and treatment-induced immunosuppression. The coronavirus disease 2019 (COVID-19) pandemic highlighted this vulnerability, particularly in aggressive tumors such as triple-negative breast cancer (TNBC) and clear cell renal cell carcinoma (ccRCC). However, the molecular mechanisms linking cancer progression with COVID-19 severity remain poorly defined. This study aimed to identify shared molecular signatures between COVID-19 and TNBC, breast cancer, and ccRCC using integrative bioinformatics approaches. Methods: A comprehensive in silico case–control analysis was conducted using publicly available GEO transcriptomic datasets (GSE164805, GSE139038, GSE45498, and GSE105261). Differentially expressed genes (DEGs) were identified by comparing mild and severe COVID-19 cases with each cancer type. Protein–protein interaction (PPI) networks were constructed to identify hub genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Regulatory networks involving microRNAs (miRNAs) and transcription factors (TFs) were also examined. Results: Shared hub genes were identified across COVID-19 and cancer datasets, including IGF1, MMP9, and NOTCH1 in TNBC; TOP2A, PXN, and CCNB1 in breast cancer; and ASPM and TTK in ccRCC. These genes are linked to immune regulation, inflammation, cell cycle control, and tumor progression. Enrichment analyses revealed convergent pathways such as MAPK signaling, cytokine–cytokine receptor interaction, Ras signaling, and proteoglycans in cancer. Key regulatory molecules, including miR-145-5p, miR-192-5p, miR-335-5p, and transcription factors NFKB1, BRCA1, and TP53, modulated both viral and oncogenic processes. Severe COVID-19 was associated with enhanced inflammatory and proliferation-related signaling across all cancer types. Conclusions: This integrative, severity-stratified analysis identifies shared molecular and regulatory features linking severe COVID-19 with aggressive cancers, highlighting persistent immune activation and altered immune communication as common underlying themes without implying causality or clinical outcome effects. These findings provide a systems-level, hypothesis-generating framework for understanding virus–cancer interactions and may inform future biomarker discovery and immune-focused therapeutic strategies in vulnerable cancer populations. Full article

Background/Objectives: Renal cell carcinoma (RCC) is a common and often asymptomatic malignancy with limited treatment options for advanced stages. Chronic inflammation and cellular senescence—collectively termed “inflammaging”—are emerging as key contributors to tumor progression. This study aimed to investigate the expression of inflammaging-related markers in RCC tissues, focusing on the role of PTX3, IL-6, and senescence-associated proteins in the tumor microenvironment. Methods: A retrospective cohort of 57 patients with clear cell RCC who underwent nephrectomy was analyzed. Formalin-fixed paraffin-embedded samples from tumor, peritumoral, and normal renal tissues were examined using confocal immunofluorescence microscopy to assess PTX3, IL-6, p21, and p16 expression. Senescence-associated β-galactosidase staining was performed to identify senescent cells. Serum IL-6 levels were measured by ELISA, and survival analysis was conducted using Kaplan–Meier curves and Cox regression analysis. Results: PTX3 and IL-6 were significantly upregulated in both peritumoral and tumor tissues compared to normal kidney samples (p < 0.001). Expression of senescence markers p21 and p16 were elevated in peritumoral areas (p < 0.001) as compared to normal renal tissues, but their expression was reduced or absent in the tumor core. High-grade and high-stage tumors exhibited stronger PTX3 and IL-6 expression and lower levels of cell cycle inhibitors (p < 0.001). Patients with elevated serum IL-6 levels had significantly lower 5-year cancer-specific survival (p < 0.005) and shorter progression-free survival (p < 0.001). Conclusions: Our findings suggest that peritumoral tissue in RCC exhibits a senescent and proinflammatory phenotype that may support tumor progression. PTX3 and IL-6 are potential biomarkers of disease severity and prognosis. Targeting inflammaging pathways could offer new therapeutic strategies for RCC, particularly in aggressive disease forms. Full article

Objective: The study aims to evaluate the diagnostic and prognostic efficacy of gut-derived trimethylamine N-oxide (TMAO) as a molecular biomarker for heart failure (HF) in comparison to the N-terminal pro-B-type natriuretic peptide. Background: The clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is frequently affected by non-cardiac physiological variables, including adiposity, advanced age, and renal clearance rates. Consequently, there is a compelling need for additional biomarkers. This analysis investigates TMAO as a critical mediator within the gut–heart axis, reflecting systemic inflammation and myocardial fibrosis secondary to intestinal dysbiosis. Methods: A comprehensive literature search was conducted using PubMed. Keywords such as “trimethylamine N-oxide”, “heart failure”, “heart failure with preserved ejection fraction” and “N-terminal pro-B-type natriuretic peptide” were used. The inclusion criteria comprised original research and literature reviews describing the pathophysiological mechanisms and clinical utility of TMAO in the context of HF diagnosis and prognosis. Results: The analyzed literature suggests that TMAO functions as an independent predictor of major adverse cardiovascular events, correlating with all-cause mortality and rehospitalization risk across all HF phenotypes. Furthermore, data indicate that using TMAO alongside NT-proBNP measurements may predict patient risk more accurately, particularly in patients where natriuretic peptide interpretation is traditionally obscured by comorbidities such as diabetes mellitus and chronic kidney disease. Conclusions: Although NT-proBNP remains the gold standard for acute diagnosis, TMAO provides significant value for long-term clinical management. By serving as a metabolic–inflammatory indicator, TMAO complements standard diagnostic panels, offering deeper insights into the prognostic trajectory and the underlying intestinal barrier integrity of patients with HF. Full article

Introduction: Telomeres, which protect chromosome ends, are important in cell replication and are altered by ageing. In the realm of organ transplantation, telomere length has emerged as a potential biomarker for predicting both graft survival and recipient longevity. This study explores the correlation of telomere length with transplant outcomes to assess whether longer telomere length is associated with better long-term graft function and patient survival. Methods: Telomere length (TL) was analysed in 274 European renal transplant pairs (donors/recipients). Recipient DNA was collected before and after kidney transplantation, and donor DNA just prior to transplant surgery. Results: Donor TL was not significantly associated with graft survival. Donor age was a significant predictor of graft failure (1.02, 95% CI: 1.01–1.03, p < 0.01). Post-transplant recipient TL had a significant association with graft survival. Longer TL was associated with an up to 90% reduction in risk of graft failure (HR = 0.10, 95% CI: 0.015–0.71, p = 0.02). Conclusions: In this study, kidney transplant recipients with longer telomere length demonstrated significantly better long-term graft survival. If validated in additional kidney transplant cohorts, recipient telomere length could serve as a valuable biomarker for improving graft failure risk stratification and enhancing the long-term care of transplant recipients. Full article

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency, accumulation of globotriaosylceramide (Gb3), and progressive multiorgan involvement. Increasing evidence indicates that oxidative stress plays a central role in disease pathogenesis. This review aims to synthesize current knowledge on the molecular mechanisms underlying oxidative stress, the relevance of oxidative damage biomarkers, and potential therapeutic implications. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using terms related to Fabry disease, Gb3 metabolism, mitochondrial and endothelial dysfunction, inflammatory signaling, and oxidative stress markers. Clinical, experimental, and translational studies were included. Available data demonstrate that Gb3 accumulation disrupts mitochondrial function and activates NADPH oxidase, NF-κB, and MAPK signaling pathways, resulting in excessive production of reactive oxygen species. These processes contribute to cellular injury, particularly within the cardiovascular, renal, and nervous systems. Biomarkers such as malondialdehyde, 8-hydroxy-2′-deoxyguanosine, glutathione redox status, and antioxidant enzyme activities appear useful for assessing oxidative burden and monitoring therapeutic responses. Overall, current evidence underscores the pivotal role of oxidative stress in the progression of Fabry disease and highlights the need for further research into targeted antioxidant and disease-modifying therapeutic strategies. Full article