Search Results (16,200)

Background: Non-Wilms renal tumours (NWRTs) are rare paediatric malignancies and account for a small but clinically significant proportion of childhood renal cancers. Due to their low incidence and biological heterogeneity, outcome data are limited, and management is largely extrapolated from international collaborative protocols. No national data describing the incidence and outcomes of NWRTs in children in the Republic of Ireland (ROI) have previously been published. Objective: To determine the incidence, treatment strategies, and survival outcomes of NWRTs in children in the ROI. Methods: A retrospective cohort study was conducted of all children under 16 years of age with histologically confirmed renal tumours diagnosed and treated at Children’s Health Ireland (CHI) at Crumlin between January 2005 and December 2025. As CHI Crumlin is the single national paediatric oncology centre in the ROI, this cohort represents national case ascertainment for the study period. A total of 143 paediatric renal tumours were identified; Wilms tumours (n = 118) were excluded, leaving 25 children (17.48%) with NWRTs for analysis. No cases of bilateral renal tumours were identified. Histological subtypes included renal cell carcinoma (RCC), clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), malignant rhabdoid tumour of the kidney (MRTK), and anaplastic sarcoma of the kidney. Demographic characteristics, treatment strategies, and survival outcomes were analysed. Results: Twenty-five children with NWRTs were identified: CCSK (n = 9), RCC (n = 7), CMN (n = 6), MRTK (n = 2), and anaplastic sarcoma of the kidney (n = 1). At a median follow-up of 107.9 months (range 4.5–181.3 months), overall survival for the cohort was 76%. Overall survival by histology was 100% for CMN, CCSK and anaplastic sarcoma, 43% for RCC, and 0% for MRTK. Treatment strategies varied by histology, with 68% undergoing upfront surgery, 32% receiving neoadjuvant chemotherapy, 60% receiving adjuvant systemic therapy, and 44% receiving radiotherapy. Tumour recurrence occurred in 4/25 patients (16%), confined to the RCC (3) and CMN (1) subgroups. Seven Event-Free Survival events were observed, comprising three RCC relapses and one RCC progression, one CMN relapse, and two MRTK progression-related deaths. No recurrences occurred in CCSK. Conclusions: NWRTs comprised 17.5% of all paediatric renal tumours diagnosed nationally during the study period and demonstrated marked heterogeneity in outcomes according to histological subtype. CMN showed excellent survival with six out of seven requiring surgery alone, whereas MRTK remained associated with dismal outcomes despite multimodal therapy. These national data support histology-driven, risk-adapted management and highlight the importance of continued international collaboration to improve outcomes in NWRTs. Full article

Acute kidney injury (AKI), a life-threatening disorder marked by abrupt renal dysfunction, is increasingly recognized as a global healthcare challenge. It not only triggers immediate organ dysfunction but also heightens long-term risks of chronic kidney disease (CKD). The senescence of proximal tubular epithelial cells (PTECs) has a major impact on the occurrence and development of AKI. This review systematically analyzes existing evidence, which suggests that the senescence of PTECs may have a dual effect. Acute cellular senescence typically mitigates uncontrolled replication of damaged cells by inducing cell cycle arrest, thereby limiting the further expansion of tissue damage. In contrast, the pathological retention of chronic senescent cells and the excessive production of the senescence-associated secretory phenotype (SASP) exacerbate the local inflammatory response and the process of fibrosis, accelerating the transformation of AKI into CKD. Despite incomplete elucidation of the spatiotemporal mechanisms governing the transition from acute to chronic cellular senescence, therapeutic interventions can be precisely targeted to specific disease stages based on their characteristic progression dynamics. This review summarizes the intervention strategies applicable at different stages of AKI, including prevention, early induction of senescence, senoreverse, senolysis, and senomorphics. Additionally, we highlight potential therapeutic targets to provide a theoretical basis for optimizing clinical management. Full article

Acute kidney injury (AKI) continues to pose a significant clinical challenge due to its high morbidity rates and limited therapeutic options. Recent evidence suggests that natural compounds may provide renoprotective benefits by modulating oxidative stress and inflammation. This study examines the protective effects of a novel polysaccharide peptide extracted from Ganoderma lucidum (GL-PPQ1) against renal ischemia–reperfusion (I/R) injury, with particular emphasis on the integrin β3/Fibronectin 1 (Fn1) signaling axis. A murine model of renal I/R injury was established, and GL-PPQ1 was administered orally for seven days before surgery. The assessment included renal function, histopathology, oxidative stress markers, and inflammatory cytokines. Additionally, transcriptomic profiling and protein expression analyses were conducted to elucidate the underlying mechanisms. The results revealed that GL-PPQ1 pretreatment significantly reduced renal tubular damage, lowered serum creatinine and blood urea nitrogen levels, and diminished oxidative stress and inflammatory responses. RNA sequencing revealed that GL-PPQ1 affected gene sets associated with extracellular matrix remodeling and cell adhesion. Western blot and immunohistochemistry further confirmed that GL-PPQ1 decreased the expression of integrin β3 and Fn1, suggesting a regulatory effect on their interaction during I/R injury. These findings demonstrate that GL-PPQ1 offers substantial kidney protection by mitigating oxidative stress, inflammation, and dysregulation of the integrin β3/Fn1 signaling pathway. Thus, this study supports that polysaccharide peptides derived from Ganoderma lucidum could have the potential to serve as both a dietary supplement and a therapeutic agent in the treatment of AKI. Full article

Zinner syndrome is a rare congenital anomaly of the male genitourinary tract, characterized by the triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ejaculatory duct obstruction. Owing to its low prevalence and nonspecific clinical presentation, diagnosis is often delayed or incidental, with imaging playing a central role in detection and characterization. This study presents a narrative review with an illustrative case report, aiming to summarize the imaging features of Zinner syndrome, outline the main radiologic differential diagnoses of seminal vesicle cysts, and highlight common diagnostic pitfalls, with emphasis on cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI). The narrative review of the literature highlights that CT and MRI are essential for accurate anatomical localization, characterization of cystic content, and identification of associated genitourinary anomalies. MRI, in particular, provides superior soft-tissue contrast and is considered the reference modality for diagnosis and differential evaluation of male pelvic cystic lesions. Key differential diagnoses include Müllerian duct cysts, prostatic utricle cysts, and ejaculatory duct cysts. As an illustrative example, we report the case of a young adult male presenting with pelvic discomfort, infertility, and mild lower urinary tract symptoms. Imaging findings, including ultrasound and cross-sectional studies, demonstrated a seminal vesicle cyst associated with ipsilateral renal agenesis, consistent with Zinner syndrome. Zinner syndrome should be considered in the evaluation of male pelvic cystic lesions, particularly in the presence of unilateral renal agenesis. Awareness of its characteristic imaging features is essential for accurate diagnosis and appropriate management, with MRI playing a pivotal role in confirming the diagnosis and distinguishing it from other pelvic cystic entities. Full article

Background: Length of stay (LOS) reflects healthcare utilization but may also capture patient clinical trajectories. We investigated the relationship between LOS categories, organ support requirements, and in-hospital mortality. Methods: This retrospective observational study included 1332 consecutive adult ICU patients in a tertiary-care center. ICU LOS patterns were categorized using median-based and predefined cutoffs. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality. Results: Prolonged ICU LOS was associated with higher crude mortality (61.0% vs. 43.5%, p < 0.001). However, in LOS-adjusted models, mortality was independently associated with mechanical ventilation (aOR 29.89, 95% CI 17.92–49.86), inotropic support (aOR 4.94, 95% CI 3.50–6.97), hemodialysis (aOR 5.43, 95% CI 2.52–11.72), older age, and diabetes mellitus. Prolonged LOS was not independently associated with mortality (aOR 0.93, p = 0.630). Conclusions: LOS reflects underlying disease severity rather than acting as an independent driver of mortality. Integrating LOS pattern assessment with markers of organ dysfunction may improve risk stratification and resource planning in hospitalized populations. Full article

Background: Earlier studies in patients with end-stage renal dysfunction (ESRD) reported no significant difference in long-term outcomes between mechanical and tissue valves after valve surgery, largely due to the limited life expectancy of this population. As survival in patients with ESRD has improved in recent years, this study evaluated whether increased life expectancy affects long-term outcomes according to valve type in patients with ESRD undergoing aortic valve replacement (AVR) using a nationwide cohort. Methods: We analyzed data from the Korean National Health Insurance Service database from January 2005 to December 2021. Among 474 patients with ESRD who underwent AVR, 279 received tissue valves and 195 received mechanical valves. Propensity score matching was performed to balance baseline characteristics, yielding 99 matched patient pairs. Results: In the matched cohort, early mortality (within 30 days) was significantly higher in the tissue valve group (16.2% vs. 4.0%; p = 0.008). However, long-term survival rates at 1, 5, and 10 years did not differ significantly between the groups (all p > 0.05). Stratification by operative era (2005–2013 vs. 2014–2021) similarly showed no significant impact of valve type on survival despite temporal advances in care. Conclusions: Long-term survival and complication rates after AVR in patients with ESRD were comparable between mechanical and tissue valves across operative eras. Valve selection should be guided by shared decision-making, incorporating individual life expectancy and comorbidity profiles rather than assuming mechanical valves as the default option. Full article

Aims: This study aimed to examine the association between three-year changes in body mass index (BMI) and the risk of new-onset or progressive diabetic kidney disease (DKD) among people with type 2 diabetes and a normal BMI at baseline. Methods: A total of 416 people with type 2 diabetes (T2DM) and a normal BMI were enrolled from the Chongqing Diabetes Registry (CDR, NCT03692884) cohort and were followed for incident DKD until 2025. The change in BMI at the three-year follow-up was classified as follows: stable BMI (<5% change), decreased BMI (≥5% reduction), and increased BMI (≥5% gain). Cox proportional hazards models were used to analyze the association between BMI change categories and DKD risk. Results: During a mean follow-up of 3.4 years, people with an increased BMI exhibited a significantly higher risk of DKD onset or progression compared with people with a stable BMI [HR = 1.67, 95%CI: 1.15–2.43, p = 0.007]. Each 1% increase in BMI was significantly associated with an increased risk of DKD onset or progression [HR = 1.05, 95%CI: 1.02–1.07, p < 0.001]. This association remained significant after multivariable adjustment. Time-dependent receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) of this indicator reached 0.683–0.729 for the prediction of new-onset or progressive DKD risk over 3–5 years. In subgroup analyses, decreased BMI was associated with a lower risk of DKD among people aged <60 years [HR = 0.21; 95% CI: 0.04–0.96; p = 0.044]. Conclusions: A ≥5% increase in BMI in three years may be a risk factor for new-onset or progressive DKD among people with T2DM and normal BMI. Conversely, a ≥5% decrease in BMI may be associated with renal protection in non-elderly individuals within the population. Full article

Resveratrol (RSV), a bioactive polyphenol, has emerged as a pleiotropic modulator within the integrated pathophysiology of cardiovascular disease (CVD) across the life course. Effective CVD management requires a transition from organ-centric frameworks to systems-level models that acknowledge dynamic crosstalk among metabolic, renal, and cardiovascular networks. Oxidative stress constitutes a central unifying axis in this interconnected biology, propagating cross-organ injury from early developmental stages onward. Mechanistically, RSV acts as a redox-responsive gene regulator by activating the Nrf2–ARE pathway, restoring nitric oxide bioavailability, and orchestrating SIRT1, AMPK, and NF-κB signaling to recalibrate mitochondrial function, inflammatory tone, and endothelial integrity. Within the Developmental Origins of Health and Disease (DOHaD) paradigm, RSV exhibits reprogramming potential that attenuates the intergenerational transmission of hypertension, kidney disease, and metabolic dysfunction. Although clinical translation is constrained by limited bioavailability and rapid metabolism, advanced delivery systems and artificial intelligence-enabled optimization strategies provide promising avenues to enhance therapeutic precision and scalability. This narrative review integrates mechanistic and translational insights to position RSV as a systems-oriented life-course intervention with sustained and intergenerational relevance in CVD. Full article

Background and Objectives: To identify predictors of pulmonary infection in critically ill patients after abdominal surgery and to develop an early postoperative risk stratification model. Materials and Methods: Medical records of ICU patients after abdominal surgery (January 2016–June 2024) with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ≥10 were retrospectively analyzed. Patients were categorized according to the presence or absence of pulmonary infection. Candidate variables were screened using LASSO regression, followed by multivariate logistic regression to identify independent predictors. A nomogram-based prediction model was constructed and internally validated. Results: Among 4852 patients, 390 (8.0%) developed pulmonary infections. Overall, 8 independent predictors were identified: Male sex (vs. female) (OR 1.509, 95% CI: 1.091–2.087, p = 0.013), chronic obstructive pulmonary disease (OR 4.139, 95% CI: 2.872–5.966, p < 0.001), atrial fibrillation (OR 2.320, 95% CI: 1.366–3.939, p = 0.002), hypertension (OR 1.869, 95% CI: 1.372–2.539, p < 0.001), chronic renal insufficiency (OR 2.412, 95% CI: 1.143–5.091, p = 0.021), preoperative total bilirubin (OR 1.003, 95% CI: 1.001–1.004, p = 0.002), rectal surgery (OR 0.354, 95% CI: 0.151–0.830, p = 0.017), and invasive mechanical ventilation duration > 6 h (OR 2.206, 95% CI: 1.628–2.990, p < 0.001). The nomogram demonstrated good discrimination (AUC: 0.734 95% CI: 0.698–0.770) and calibration. Conclusions: This study identified 8 independent predictors of pulmonary infection and developed an internally validated early postoperative risk stratification model with satisfactory performance. The model may assist clinicians in identifying high-risk patients and guiding timely preventive strategies in ICU practice. Full article

Background: Fibroblast growth factor-23 (FGF23) is a key regulator of phosphate homeostasis and an emerging biomarker in cardiovascular disease. Emerging data suggest that FGF23 may also contribute to the pathophysiology of myocardial infarction (MI), but existing studies have largely focused on non-acute stages. To address this gap, we investigated early FGF23 regulation by characterizing serum concentration kinetics over the first 24 h following MI, using both a clinical MI model (TASH) and a cohort of patients with ST-elevation myocardial infarction (STEMI). Methods: Circulating FGF23 concentrations (cFGF23; RU/mL) were determined by C-terminal ELISA in patients with preserved renal function (eGFR > 30 mL/min/1.73 m²). TASH (transcoronary septal ablation) was carried out in patients with hypertrophic obstructive cardiomyopathy (n = 38). Venous serum samples were taken at baseline (pre-TASH) and at 30′, 60′, 2 h, 4 h and 24 h post-TASH. For the STEMI cohort (n = 18), serum was sampled immediately before and 3 h after coronary recanalization. All samples were processed using standardized procedures prior to analysis. Changes over time were assessed using the Friedman test with Bonferroni-corrected pairwise Wilcoxon comparisons. Results: FGF23 concentrations changed significantly over time after TASH (Friedman test, p < 0.000001, Kendall’s W = 0.518). Baseline FGF23 was 28.9 (19.4–71.0) RU/mL and increased significantly at 30′ (68.2 (36.2–178.7) RU/mL, adjusted p < 0.0001 **) after TASH. Concentrations remained elevated at 60′ (54.8 (31.6–118.3) RU/mL; adjusted p = 0.0019 *), returned to baseline at 2 h (30.9 (20–71.2) RU/mL; adjusted p = 1.0 vs. baseline) and decreased significantly below baseline at 4 h (24 (12.13–37.5) RU/mL, adjusted p = 0.0215 *). By 24 h, FGF23 had returned to baseline levels (28.8 (12.8–57.3) RU/mL; adjusted p = 1.0 vs. baseline). Although concentrations were numerically higher than at the 4 h nadir, this recovery did not reach statistical significance (adjusted p = 0.136 vs. 4 h). In STEMI patients, a non-significant decrease was observed from baseline (27 (15.5–35.75) RU/mL) to 3 h after recanalization (15.5 (6.75–34.25) RU/mL; p = 0.074, effect size r = 0.422). In an exploratory normalized analysis, the decline reached significance (p = 0.0241). Conclusions: The triphasic kinetics of circulating FGF23 in TASH patients—characterized by an early rise, transient undershoot, and a recovery toward baseline with a continuing upward trend—are consistent with a dynamic release-and-clearance pattern following myocardial injury. These findings are hypothesis-generating and warrant further investigation in larger cohorts with additional biomarkers to elucidate the source, regulation, and potential functional significance of FGF23 in the acute phase of myocardial infarction. Full article

Background/Objectives: Cell-free DNA (cfDNA) is released into the circulation during inflammation-driven cellular injury and regulated cell death. Elevated cfDNA concentrations have been reported in several clinical settings, including chronic kidney disease, hemodialysis, and peritoneal dialysis (PD). We previously demonstrated that PD-related peritonitis induces an increase in circulating cfDNA; however, the mechanisms underlying cfDNA generation remained unclear. This study aimed (i) to confirm peritoneal cfDNA variation following peritonitis in PD patients, and (ii) to elucidate the apoptotic pathways responsible for cfDNA release. Methods: Fifty-four PD patients were enrolled and stratified into the following groups: Group A—no history of peritonitis (n = 25); Group B—remote peritonitis > 3 months prior (n = 21); Group C—recent peritonitis < 3 months prior (n = 8). cfDNA was quantified by qPCR. Apoptosis was assessed qualitatively by DNA laddering and quantitatively using ELISA assays for Caspase-3, Caspase-8 and Caspase-9. Results: cfDNA levels were significantly higher in patients with recent peritonitis compared to both other groups (p < 0.01). DNA laddering showed enhanced nucleosomal fragmentation, consistent with apoptosis. Caspase-3 concentrations were markedly increased in recent peritonitis (<3 months) and significantly correlated with cfDNA levels (ρ = 0.511, p < 0.01). Both Caspase-8 and Caspase-9 correlated with Caspase-3 (ρ = 0.57 and ρ = 0.47, respectively), indicating engagement of both extrinsic and intrinsic apoptotic pathways. Conclusions: In conclusion, peritoneal cfDNA in PD patients with peritonitis originates primarily from apoptosis and reflects dual-pathway caspase activation. cfDNA and Caspase-3 progressively decline with longer time elapsed from peritonitis, supporting their potential use as biomarkers for inflammatory activity and membrane recovery. Full article

Bartter syndrome (BS) represents a group of rare, autosomal recessive renal tubular disorders characterized by hypokalemic hypochloremic metabolic alkalosis, secondary hyperaldosteronism, and normal to low blood pressure. The underlying pathophysiology is primarily driven by defects in critical ion transport proteins or channels localized within the thick ascending limb of the loop of Henle, leading to impaired salt reabsorption. Recent advances in molecular genetics have refined the classification of Bartter syndrome. Current evidence supports SLC12A1, KCNJ1, CLCNKB, BSND, and MAGED2 as the core disease genes within the contemporary BS spectrum, with MAGED2 causing a distinct X-linked transient antenatal form. In contrast, gain-of-function CASR variants, historically labeled “type V Bartter syndrome”, are now more appropriately described as CaSR-associated Bartter-like phenotypes within the broader spectrum of disorders of calcium homeostasis. Despite significant progress, two primary research limitations remain. First, fully elucidating genotype–phenotype correlations and overcoming diagnostic complexities continues to be highly challenging due to substantial phenotypic overlap and genetic heterogeneity. Compounding these diagnostic hurdles is the equally critical challenge of understanding mutation-driven pathogenic mechanisms to develop viable clinical interventions. This review systematically summarizes the current molecular genetic landscape of BS to address these gaps. We highlight the relationships between specific genetic variants and clinical manifestations, delve into molecular pathophysiology including protein misfolding and trafficking defects, and explore emerging therapeutic approaches such as molecular chaperones. By integrating genetic and clinical data, this work aims to provide a comprehensive framework to facilitate precise diagnosis and individualized treatment strategies, ultimately advancing precision medicine in the management of Bartter syndrome. Full article

Chronic kidney disease is a global public health concern, representing a critical global public health challenge with increasing morbidity and mortality rates. The disease is a long-term condition characterized by the progressive loss of renal function. Early detection of declining kidney health and timely intervention are crucial to slow disease progression and improve prognosis, mitigating complications, including cardiovascular events. Current diagnostic standards are unable to detect early stages of kidney disease, reflecting early signs of glomerular and tubular damage. This creates an urgent need to identify reliable biomarkers for early detection, prognosis and therapeutic monitoring of kidney diseases. Novel biomarkers, including urinary microRNA, exosomal components, proteomic signatures and integrated multi-omics profiles, facilitated by up-to-date technologies offer strong promise for enhancing early diagnosis, risk assessment and monitoring of the disease. We focus on the fundamental biological significance and clinical application of these markers, discussing a critical evaluation of novel methodologies and clinical evidence supporting their potential for earlier and more precise diagnosis. This review summarizes innovative urinary biomarkers and advanced analytical technologies that can provide a more comprehensive and accurate assessment of the kidney status towards early diagnosis, better prognosis and better quality of life for patients with chronic kidney disease. Full article

Saskatoon berry (SB), a traditional food of Indigenous people, has been associated with cardiometabolic benefits in animal models; however, its effects on humans remain unclear. This study investigated the effects of dried SB consumption on cardiometabolic outcomes, gut microbiota, and short-chain fatty acids (SCFAs) profiles in healthy adults. In a 10-week, single-arm, and open-label trial, 20 healthy adults consumed 40 g/day of freeze-dried whole SB. Biochemical measures, physical exams, dietary records, participant feedback, and fecal samples were collected before and after the intervention. Gut microbiota composition and fecal SCFAs were profiled using 16S-rRNA sequencing and gas chromatography–mass spectrometry, respectively. SB intake significantly reduced fasting plasma glucose, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), non-high-density lipoprotein-cholesterol (non-HDL-c), systolic blood pressure, and high-sensitivity C-reactive protein, while increasing dietary fiber intake. Fiber intake was negatively correlated with TC, LDL-c and non-HDL-c (p < 0.05). The relative abundance of fecal Prevotellaceae increased after SB consumption and was positively correlated with multiple fecal SCFAs (p < 0.05–0.0001), while being negatively associated with lipid profiles and blood pressure. No adverse cardiovascular, hepatic, or renal dysfunction were observed; however, the significant increase in sugar intake may pose a risk for elevated blood glucose. Therefore, limiting other high-sugar foods during SB supplementation may be advisable for individuals with glucose intolerance. Overall, SB intake improved glucose and lipid metabolism and lowered blood pressure and inflammatory markers in healthy adults. These cardiometabolic benefits may be mediated by fiber and anthocyanins in SB and through modulation of gut microbiota and SCFA production; however, further confirmation is needed in subsequent randomized controlled trials. Full article

Early diagnosis of chronic kidney disease (CKD) remains a major clinical challenge. Periostin (POST) and kidney injury molecule-1 (KIM-1) have been proposed as biomarkers of tubular injury and fibrosis. This study aimed to evaluate their utility as markers associated with CKD stage and their associations with renal function and proteinuria in children. Twenty-three children with CKD stages I–IV and 23 healthy controls were enrolled. Serum and urinary POST and KIM-1 were measured together with creatinine (CR), cystatin C (CysC), proteinuria, albuminuria, and urinary α1- and β2-microglobulin. Patients were classified as early stage (ES; CKD I–II) or late stage (LS; CKD III–IV). Serum and urinary POST and KIM-1, uPOST/CR, uKIM-1/CR, fractional excretion indices (FePOST, FeKIM-1), and UPCR were higher in CKD patients than in controls. Absolute biomarker concentrations did not differ between ES and LS and were not associated with eGFR, UPCR, UACR, or tubular protein excretion. In contrast, uPOST/CR, uKIM-1/CR, FePOST, and FeKIM-1 increased with CKD stage, were higher in LS than ES, correlated positively with CysC, and inversely with eGFR. FePOST and FeKIM-1 also correlated strongly with tubular protein markers. The FePOST/FeKIM-1 ratio was elevated in ES patients compared with controls and remained stable across CKD stages. Fractional excretion of POST and KIM-1 is associated with CKD stage and reflects ongoing tubular injury in children. The FePOST/FeKIM-1 ratio may represent a sensitive marker of early CKD. Full article