Search Results (372)

Accurate segmentation of renal anatomical structures is essential for informed clinical decision-making in nephropathology, supporting precise diagnosis, treatment planning, and longitudinal monitoring of kidney diseases. In this work, we propose an Edge-Aware U-Net architecture with Boundary-Sensitive Optimization, specifically designed to address the challenges of fine anatomical boundary delineation in histopathological images. Comprehensive benchmarking against state-of-the-art models including U-Net, Attention U-Net, and ResUNet demonstrates robust quantitative performance alongside strong potential for clinical deployment. The proposed model achieves superior boundary preservation, reflected by a high structural similarity index (SSIM: 0.9473), while maintaining computational efficiency with an average inference time of 52 ms per image. It further outperforms existing methods across key image quality metrics, including PSNR (17.269 dB), MAE (0.0266), and RMSE (0.0321). Clinical validation indicates statistically significant improvements in glomerular detection (p < 0.01) and effective tubulointerstitial differentiation (F1-score: 0.891), with consistent performance observed across multiple staining protocols. Full article

Cultured urine-derived cells (UDCs) have been proposed as a source of material for the RNA-based molecular diagnosis of genetic disorders. Previous studies have shown that UDCs can be clonally expanded, passaged, frozen, regrown and have some stem cell characteristics, but their anatomic origin and diagnostic utility remain insufficiently explored. In this study, we cultured UDCs from 40 individuals (aged 4 to 20 years; 21 females) and extracted RNA for sequencing. We compared UDC gene expression to that of marker genes of the kidney and urinary tract segments. UDC gene expression most closely matched marker genes of parietal epithelial cells that line the inner surface of Bowman’s capsule in the kidney glomerulus. UDCs expressed VCAM1 (CD106) and POUF51 (OCT4), consistent with a progenitor cell type. UDCs also expressed 54.4% of 3125 OMIM-listed disease-causing genes. This indicated that UDCs can be used to diagnose a similar number of genetic disorders as skin fibroblasts and a wider range of genetic disorders than can be analysed by RNA extracted from whole blood. In conclusion, UDCs are a non-invasive cell source for RNA sequencing that is suitable for investigating a broad range of conditions. Full article

Background/Objectives: Contrast-associated acute kidney injury (CA-AKI) remains an important cause of morbidity and mortality in patients undergoing procedures that require intravascular contrast administration. Therefore, the early identification of high-risk individuals is paramount, above all for ST-segment elevation myocardial infarction (STEMI) patients in need of urgent percutaneous coronary intervention (PCI). Methods: This retrospective study evaluated the prognostic value of the Pan-Immune-Inflammation Value (PIV), a composite inflammatory index, in predicting CA-AKI among patients presenting with STEMI who received urgent PCI within a 12 h window from the onset of symptoms. Results: This study recruited 2325 patient. CA-AKI was defined as a >25% or ≥0.5 mg/dL increase in serum creatinine within 48–72 h after the procedure. Patients were categorized into CA-AKI (+) and CA-AKI (−) groups. PIV levels were significantly higher in patients who developed CA-AKI (502.5 ± 324.5 vs. 264.7 ± 165.8; p < 0.001). ROC analysis identified a PIV cutoff value of >320, yielding an AUC of 0.753 (95% CI: 0.740–0.787; p < 0.001), with 67% sensitivity and 66.9% specificity. Multivariate logistic regression confirmed that PIV > 320 independently predicted CA-AKI (OR 2.118; 95% CI: 1.329–3.790; p < 0.001). In multivariable analysis, age, Killip class, contrast volume, and PIV > 320 were identified as independent predictors of CA-AKI. Conclusions: Elevated admission PIV serves as an independent and practical biomarker for predicting CA-AKI in STEMI patients undergoing PCI. Full article

The discovery of apolipoprotein L1 (APOL1) risk polymorphisms has significantly changed our knowledge of kidney disease susceptibility and development in African American populations. Several non-diabetic kidney disorders, such as focal segmental glomerulosclerosis (FSGS), collapsing glomerulopathy, HIV-associated nephropathy (HIVAN), and accelerated chronic kidney disease (CKD) development, are significantly more likely to occur in people with two coding variations, G1 and G2. The significance of context-dependent pathogenic processes is highlighted by the poor penetrance and remarkable phenotypic variety of APOL1-associated kidney disease, despite its substantial impact. This review synthesizes current knowledge of APOL1 biology through a molecular framework, emphasizing gain-of-toxic-function effects of risk variants in podocytes, dysregulated ion fluxes, mitochondrial dysfunction, impaired proteostasis, and activation of innate immune and inflammatory signaling pathways. We describe how the well-recognized “second-hit” paradigm has a biological basis, driven by strong inducibility by interferons and immunological activation, as well as strict basal regulation of APOL1 expression. Lastly, we explore future approaches to precision nephrology and highlight translational advancements, such as APOL1 gene-silencing techniques. This review provides a mechanistic roadmap for translating APOL1 biology into targeted therapeutic strategies by integrating genetics, cell biology, immunology, and systems-level approaches. Full article

Background: Focal segmental glomerulosclerosis (FSGS) is a leading cause of renal disease presenting with steroid-resistant nephrotic syndrome (SNRS) and variable stages of chronic kidney disease (CKD). Monogenic etiologies for FSGS are increasingly recognized, particularly in pediatric and familial cases. Missense variants in the MAF BZIP Transcription Factor B (MAFB) gene cause a dominantly inherited condition with variable phenotype, ranging from isolated ocular or renal manifestations to syndromic FSGS. Methods: Detailed clinical and genetic investigations were conducted in an extended family presenting with a spectrum of renal and extra-renal manifestations. Results: Using Exome Sequencing (ES), a heterozygous variant, c.797T>C; p.(Leu266Pro) in the MAFB gene was identified in multiple affected family members. Variant segregation confirmed its presence in additional family members. The proband exhibited CKD accompanied by congenital auricular anomalies, hearing loss, and neurodevelopmental delay. An affected sibling presented with nephrotic-range proteinuria, Duane retraction syndrome (DRS) and neurodevelopmental involvement, while another family member had an isolated renal phenotype. Several of these features have not been previously associated with MAFB. Tools for structural modeling and stability predictions supported the functional impact of this variant. Conclusions: Our findings expand the phenotypic spectrum of MAFB-associated disease and further emphasize its variability. Full article

Primary glomerulonephritis encompasses a diverse group of kidney diseases with variable clinical trajectories and outcomes. Accurate prognostic stratification is critical for guiding individualized management and improving long-term renal survival. This narrative review synthesizes current evidence on the prognostic value of histological grading systems, circulating and urinary biomarkers, and integrative risk prediction models across major primary glomerulonephritis subtypes, including IgA nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis. Emphasis is placed on the utility of established classification systems (e.g., Oxford, MEST-C, chronicity scores), emerging tissue and fluid biomarkers (e.g., PLA2R antibodies, complement components, cytokine profiles), and the validation of multivariable prognostic tools and nomograms. We highlight areas of convergence between histopathologic lesions and molecular markers, as well as the evolving role of machine learning in predictive modeling. Ultimately, combining morphological, biochemical, and algorithmic tools holds promise for precision risk assessment and treatment tailoring in primary glomerulonephritis. Full article

Background: Congenital renal masses in neonates are most commonly congenital mesoblastic nephroma or, less frequently, or Wilms tumor. We describe a neonate with an apparent primary renal tumor that proved to be adrenal neuroblastoma infiltrating the kidney, highlighting diagnostic pitfalls in this subgroup of patients. Methods: We retrospectively reviewed the diagnostic work-up, histopathology, genomic profiling, treatment, and outcome of a term neonate in whom a renal mass was detected incidentally on ultrasound. Results: Ultrasound and MRI showed a 2 cm solid lesion centered in the upper pole of the left kidney, interpreted as nephroblastomatosis/early Wilms tumor. Left nephrectomy with adrenalectomy revealed stroma-poor, undifferentiated neuroblastoma with regional node involvement and multiple segmental chromosomal aberrations, including 1p and 3p loss, but no MYCN or ALK alterations. Initial management consisted of surgery alone with close surveillance. Within weeks, early disseminated relapse with bone and soft-tissue metastases occurred, necessitating escalation to high-risk, COJEC-based chemotherapy; resection of residual mass; and modified consolidation without high-dose chemotherapy or radiotherapy. The child remains in complete remission with preserved renal function. Conclusions: Neuroblastoma should be considered in the differential diagnosis of congenital “renal” masses. Imaging-driven provisional diagnoses may be misleading, and genomic risk profiling may help lower the threshold for systemic therapy in selected cases. Full article

Background: Patients with peripheral arterial disease (PAD) undergoing endovascular revascularization remain at high risk of long-term mortality. While anatomical characteristics such as the length of the lesion, chronic total occlusions and multi-segmental distribution strongly influence revascularization strategy and limb outcomes, their prognostic impact on survival is less clearly defined. The combination of clinical comorbidities, clinical limb presentation and anatomical factors may help to better predict mortality rate before endovascular lower limb revascularization. The primary endpoint of this study was to identify independent predictors of mortality in PAD patients, and the secondary endpoint was to develop a simple clinical risk score for individualized prognostic stratification. Methods: We conducted a single-center retrospective observational study including 476 consecutive PAD patients undergoing endovascular revascularization over a 6-year period. The endpoint target considered was all-cause mortality. Cox proportional hazards regression was used to identify independent predictors of mortality. A prognostic model was derived and subsequently simplified into a point-based clinical risk score (GZ-PAD Mortality Score). Model performance was assessed within the study cohort using Kaplan–Meier survival stratification and receiver operating characteristic (ROC) analysis. Results: Multivariable analysis identified age (HR 1.041 per year, p < 0.001), coronary artery disease (CAD) (HR 1.56, p < 0.001), chronic kidney disease (CKD) (HR 1.52, p = 0.038), dialysis dependence (HR 2.50, p < 0.001), and tissue loss (Rutherford 5–6; HR 5.33, p < 0.001) as independent predictors of mortality, whereas anatomical variables such as lesion length, chronic total occlusions and poor run-off vessel lost prognostic significance. For each patient, the linear predictor (XBETA) was calculated from the coefficients of the final Cox regression model and used to build the mortality score. Based on the 33rd and 66th percentiles of the XBETA distribution, patients were stratified into three prognostic categories: low risk (XBETA ≤ −0.43081), moderate risk (−0.43080 to 0.50835), and high risk (>0.50836). Kaplan–Meier analysis showed a significant discrimination (log-rank χ² = 102.441; p < 0.001) and good discriminative performance (AUC 0.752). Next the model based on the XBETA predictor was simplified into the global ischemic-systemic risk score (GZ-PAD) assigned for ages 60–69 years = 1 point; 70–79 years = 2 points; ≥80 years = 3 points, CAD = 2 points; CKD = 1 point; Dialysis dependence = 3 points; and tissue loss = 6 points. The new model assessed with survival curves provided robust risk stratification across low-, moderate-, and high-risk groups (log-rank χ² = 88.883; p < 0.001) and preserved predictive accuracy (AUC 0.769). Conclusions: In PAD patients undergoing successful endovascular revascularization, long-term survival appeared to be related to systemic clinical factors and ischemic severity rather than anatomical lesion complexity. The GZ-PAD Mortality Score offers a simple and clinically applicable tool for mortality risk stratification. Further studies, including external validation in independent and multicenter cohorts, are needed to confirm the robustness and generalizability of the proposed risk score. 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/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to investigate the role of this pathway in IgAN and examine related tissue inflammatory markers. Methods: We analyzed 63 biopsy-confirmed patients with IgAN and performed immunohistochemical analysis on renal samples. A panel of antibodies targeting the JAK/STAT pathway, including JAK2, JAK3, p-STAT, STAT3, and MAPK/ERK, was used for this analysis. Six kidney tumor border samples were used as controls. Additionally, CD68 staining was used to evaluate tissue inflammation in the kidney biopsies. Results: Patients with IgAN showed a significantly higher cellular density of JAK3 staining at the glomerular level compared to controls, indicating JAK3 activation (p < 0.0002). Nevertheless, the correlation between JAK3 positivity in glomeruli and clinical parameters such as the initial and final estimated glomerular filtration rate (eGFR) and proteinuria was not statistically significant. Identical results were obtained with CD68+ macrophage counts in the glomerular compartment, which did not show any correlation with clinical parameters, while CD68+ tubulointerstitial staining demonstrated a significant correlation with both initial (p = 0.002) and final eGFRs (p = 0.0014), proteinuria (p = 0.010), and interstitial fibrosis (p < 0.001), as well as with renal disease progression (p = 0.005). Conclusions: Activation of the JAK/STAT pathway was observed in patients with IgAN relative to controls, notwithstanding the inability to assess the full pathway due to technical limitations. Macrophage CD68 staining in the tubulointerstitial area increased and was associated with clinical and laboratory parameters such as eGFR and proteinuria. Additionally, MEST-C histological parameters, such as segmental glomerulosclerosis (S0/S1), tubular atrophy/interstitial fibrosis (T0/T1/T2), and crescents (C0/C1/C2), were associated with a higher number of CD68+ cells. Full article

Artificial intelligence (AI) is rapidly reshaping adult cardiac surgery, enabling more accurate diagnostics, personalized risk assessment, advanced surgical planning, and proactive postoperative care. Preoperatively, deep-learning interpretation of ECGs, automated CT/MRI segmentation, and video-based echocardiography improve early disease detection and refine risk stratification beyond conventional tools such as EuroSCORE II and the STS calculator. AI-driven 3D reconstruction, virtual simulation, and augmented-reality platforms enhance planning for structural heart and aortic procedures by optimizing device selection and anticipating complications. Intraoperatively, AI augments robotic precision, stabilizes instrument motion, identifies anatomy through computer vision, and predicts hemodynamic instability via real-time waveform analytics. Integration of the Hypotension Prediction Index into perioperative pathways has already demonstrated reductions in ventilation duration and improved hemodynamic control. Postoperatively, machine-learning early-warning systems and physiologic waveform models predict acute kidney injury, low-cardiac-output syndrome, respiratory failure, and sepsis hours before clinical deterioration, while emerging closed-loop control and remote monitoring tools extend individualized management into the recovery phase. Despite these advances, current evidence is limited by retrospective study designs, heterogeneous datasets, variable transparency, and regulatory and workflow barriers. Nonetheless, rapid progress in multimodal foundation models, digital twins, hybrid OR ecosystems, and semi-autonomous robotics signals a transition toward increasingly precise, predictive, and personalized cardiac surgical care. With rigorous validation and thoughtful implementation, AI has the potential to substantially improve safety, decision-making, and outcomes across the entire cardiac surgical continuum. Full article

The aquaporin 0 (AQP0)/major intrinsic protein of eye lens (MIP) cDNA was cloned and sequenced. Initial studies of the tissue distribution of mRNA expression proved to be incorrect. Subsequent experiments showed that AQP0 mRNA is expressed strongly in the eye with moderately strong expression in the kidneys and some expression was seen in the brain and muscle tissue, and very low expression in the esophagus/fundic stomach. Another set of PCR reactions with five times the amount of cDNA additionally showed mRNA/cDNA expression in the liver, rectal gland, and a very low level in the intestine. Sporadic expression of different pieces of AQP0 cDNA was seen in various experiments in gill and pyloric stomach. A custom polyclonal antibody was produced against a region near the C-terminal end of the AQP0 protein sequence. The antibody gave a band of around the correct size (for the AQP0 protein) on the Western blot, which also showed a few other higher-molecular-weight bands. The antibody was also used in immunohistochemistry, and in the kidney, it showed staining in the proximal II (PII), intermediate segment I (IS I), and late distal tubule (LDT) parts of the sinus zone region of nephrons as well as some staining in the bundle zone tubule segments, suggesting a role for AQP0 as a water channel. In the rectal gland, the antibody showed weak apical membrane staining in a few secretory tubules near the duct, but also somewhat stronger staining in cells appearing to connect various secretory tubules, suggesting a role in cell–cell adhesion. In the spiral valve intestine side wall and valve flap, after signal amplification, weak antibody staining was seen in the apical and lateral membranes of epithelial cells adjacent to the luminal surface. There was also some staining in the intestinal muscle. In the rectum/colon, staining was seen in a layer of cells underlying the epithelium and in some muscle layers. In the gill, there was very weak staining in secondary lamellae epithelial cells and in connective tissue surrounding blood vessels and blood sinuses. The low level of transcript expression in the rectal gland, gill, and intestinal tissues suggests caution in the interpretation of the immunohistochemical staining in these tissues. Full article

The downregulation of Klotho in renal injury predicts the progression of chronic kidney disease (CKD). Klotho acts as an antagonist of the Wnt/β-catenin pathway, which is involved in the pathogenesis of proteinuria, glomerulosclerosis and tubulointerstitial fibrosis. We investigated whether losartan (L, angiotensin II type-1 receptor blocker) alone or combined with synthetic (tempol, T) or natural antioxidants (olive leaf extract, O) could alter Klotho/Wnt4/β-catenin signaling, thus reducing fibrosis and slowing the progression of focal segmental glomerulosclerosis (FSGS) in spontaneously hypertensive rats (SHR). The rats were divided into five groups. The control rats received a vehicle. The other groups received adriamycin (2 mg/kg, i.v., twice in a 3-week interval) for FSGS induction. Treatments with L, L+T and L+O (10, 10 + 100 and 10 + 80 mg/kg/day, respectively) were administered by gavage during six weeks. In the kidneys of model rats, Klotho and Wnt4 were downregulated, whereas β-catenin and fibronectin levels were increased compared with the control group. L+T did not alter Klotho, Wnt4 or fibronectin levels, while it further increased β-catenin. In contrast, L+O improved Klotho, and reduced β-catenin and fibronectin levels, although it increased PAI-1. The L+O combination reduced proteinuria more efficiently than L and decreased renal injury close to control levels. Although these findings indicate that combined treatment of losartan and olive leaf extract is promising in slowing the progression of the experimental FSGS, further clinical studies are needed to confirm its favorable outcomes and safety in CKD patients. Full article

Background/Objectives: Neovascularization, defined as the sprouting of new blood vessels from pre-existing vasculature, is a critical pathological feature in ocular diseases such as pathological myopia and represents a leading cause of corneal vision loss. Vascular endothelial growth factor A (VEGFA) plays a pivotal role in endothelial cell proliferation, migration, survival by anti-apoptotic signaling, and vascular permeability. Dysregulation of VEGFA is closely linked to pathological neovascularization. Exosomes, nanosized phospholipid bilayer vesicles ranging from 30 to 150 nm, have emerged as promising gene delivery vehicles due to their intrinsic low immunogenicity, superior cellular uptake, and enhanced in vivo stability. This study aimed to investigate whether highly purified mesenchymal stem cell (MSC)-derived exosomes loaded with VEGFA siRNA labeled with FAM can effectively suppress pathological corneal neovascularization (CNV) via targeeted cellular transduction and VEGFA inhibition. Furthermore, we examined whether the therapeutic effect involves the modulation of the PI3K–Akt–Caspase-3 signaling axis. Methods: Exosomes purified by chromatography were characterized by electronmicroscopy, standard marker immunoblotting, and nanoparticle tracking analysis. In vitro, we assessed exosome uptake and cytoplasmic release, suppression of VEGFA mRNA/protein, cell viability, and apoptosis. In a mouse CNV model, we evaluated tissue reach and stromal retention after repeated intrastromal injections; anterior segment angiogenic indices; CD31/VEGFA immunofluorescence/immunoblotting; phosphorylated PI3K and Akt; cleaved caspase-3; histology (H&E); and systemic safety (liver, kidney, and spleen). Results: Exosomes were of high quality and showed peak efficacy at 48 h, with decreased VEGFA mRNA/protein, reduced viability, and increased apoptosis in vitro. In vivo, efficient delivery and stromal retention were observed, with accelerated inhibition of neovascularization after Day 14 and maximal effect on Days 17–19. Treatment reduced CD31 and VEGFA, decreased p-PI3K and p-Akt, and increased cleaved caspase-3. Histologically, concurrent reductions in neovascularization, inflammatory cell infiltration, and inflammatory epithelial thickening were observed, alongside a favorable systemic safety profile. Conclusions:VEGFA siRNA-loaded exosomes effectively reduce pathological CNV via a causal sequence of intracellular uptake, cytoplasmic release, targeted inhibition, and phenotypic suppression. Supported by consistent PI3K–Akt inhibition and caspase-3–mediated apoptosis induction, these exosomes represent a promising local gene therapy that can complement existing antibody-based treatments. Full article

The elevated morbidity and mortality of kidney cancer make the precise, automated segmentation of kidneys and tumors essential for supporting clinical diagnosis and guiding surgical interventions. Recently, the segmentation of kidney tumors has been significantly advanced by deep learning. However, persistent challenges include the fuzzy boundaries of kidney tumors, multi-scale problems with kidney and renal tumors regarding location and size, and the strikingly similar textural characteristics of malignant lesions and the surrounding renal parenchyma. To overcome the aforementioned constraints, this study introduces a boundary-enhanced multi-scale feature fusion network (BEMF-Net) for endoscopic image segmentation of kidney tumors. This network incorporates a boundary-selective attention module (BSA) to cope with the renal tumor boundary ambiguity problem and obtain more accurate tumor boundaries. Furthermore, we introduce a multi-scale feature fusion attention module (MFA) designed to handle 4 distinct feature hierarchies captured by the encoder, enabling it to effectively accommodate the diverse size variations observed in kidney tumors. Finally, a hybrid cross-modal attention module (HCA) is introduced to conclude our design. It is designed with a dual-branch structure combining Transformer and CNN, thereby integrating both global contextual relationships and fine-grained local patterns. On the Re-TMRS dataset, our approach achieved mDice and mIoU scores of 91.2% and 85.7%. These results confirm its superior segmentation quality and generalization performance compared to leading existing methods. Full article