Search Results (5,109)

Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL⁻¹. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC. Full article

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), initially developed for glycemic control in type 2 diabetes, have demonstrated robust cardiovascular and renal benefits. Emerging evidence suggests that these agents may also affect valvular pathobiology, particularly in degenerative aortic stenosis (AS), through anti-inflammatory and antifibrotic mechanisms. Objectives: This study evaluated whether SGLT2 inhibitor use is associated with improved clinical outcomes in degenerative AS, including all-cause mortality and the need for SAVR or TAVR, recognizing that these endpoints represent surrogate rather than direct measures of valve hemodynamic progression. Methods: A retrospective cohort analysis was conducted using TriNetX, a federated electronic medical record-based research network. Diagnoses are captured using ICD-9/ICD-10-CM codes and medications using ATC codes. Adults with non-rheumatic AS were stratified by SGLT2 inhibitors use. Propensity score matching (1:1) was performed to balance baseline characteristics between treated and untreated groups (n = 10,912 per group). Primary outcomes included all-cause mortality, TAVR, and SAVR during follow-up. Echocardiographic parameters (AVA, Vmax, mean gradient) were not systematically available. Results: After adjustment for comorbidities, SGLT2 inhibitor use was independently associated with lower all-cause mortality (6.15% vs. 9.34% HR 0.595; 95% CI 0.552–0.641; p < 0.001), TAVR (2.81% vs. 2.89% HR 0.835; 95% CI 0.746–0.934; p = 0.002), SAVR (1.28% vs. 1.90% HR 0.514; 95% CI 0.442–0.599; p < 0.001), cardiac arrest (0.82% vs. 1.21% HR 0.71; 95% CI 0.582–0.867; p < 0.001), and end-stage kidney disease (0.40% vs. 1.0% HR 0.292; 95% CI 0.222–0.384; p < 0.001). Although these associations may suggest slower disease progression, interpretation is limited by the lack of systematic echocardiographic follow-up. Conclusions: In addition to their established benefits in heart failure and renal protection, SGLT2 inhibitors may have valve-preserving effects in degenerative AS. Because true hemodynamic progression could not be evaluated, these results should be viewed as associations with surrogate clinical endpoints. Prospective studies with standardized imaging are required to determine whether SGLT2 inhibition can directly alter the course of this currently untreatable disease Full article

Background/Objectives: Diabetes mellitus and hypertension are the first and second most common causes of chronic kidney disease, respectively. Despite improvements in elucidating the pathophysiology behind these diseases and the expansion of the therapeutic armamentarium, the knowledge about the implicated genes, epigenetics, and biological pathways is limited. Methods: We sought to define diabetic nephropathy-specific and hypertensive nephropathy-specific gene signatures in human glomeruli through computational systems biology approaches. Results: Gene expression data of human glomeruli from patients with diabetic kidney disease (DKD) and hypertensive nephropathy (HTN) were collected and compared to gene expression patterns from healthy kidneys. Pathways were identified with functional enrichment analysis of DEGs. Transcription factor enrichment analysis, protein–protein interaction network expansion, and kinase enrichment analysis were also performed. Finally, novel drugs and small-molecule compounds that may reverse the kidney-specific phenotype of these disorders have been identified. Conclusions: These data suggest putative expansion of the therapeutic armamentarium in DKD and HTN, underscoring that understanding the molecular mechanisms occurring within tissue in kidney diseases may guide personalized therapy. Full article

Background/Objectives: Transmission electron microscopy (TEM) is an essential tool for diagnosing renal diseases. It produces high-resolution visualization of glomerular and mesangial ultrastructural features. However, manual interpretation of TEM images is labor-intensive and prone to interobserver variability. In this study, we introduced and evaluated deep learning architectures based on YOLOv8-OBB for automated detection of six ultrastructural features in kidney biopsy TEM images: glomerular basement membrane, mesangial folds, mesangial deposits, normal podocytes, podocytopathy, and subepithelial deposits. Methods: Building on our previous work, we propose a modified YOLOv8-OBB architecture that incorporates three major refinements: a grayscale input channel, a high-resolution P2 feature pyramid with refinement blocks (FPRbl), and a four-branch oriented detection head designed to detect small-to-large structures at multiple image scales (feature-map strides of 4, 8, 16, and 32 pixels). We compared two pretrained variants: our previous YOLOv8-OBB model developed with a grayscale input channel (GSch) and four additional feature-extraction layers (4FExL) (Pretrained + GSch + 4FExL) and the newly developed (Pretrained + FPRbl). Results: Quantitative assessment showed that our previously developed model (Pretrained + GSch + 4FExL) achieved an F1-score of 0.93 and mAP@0.5 of 0.953, while the (Pretrained + FPRbl) model developed in this study achieved an F1-score of 0.92 and mAP@0.5 of 0.941, demonstrating strong and clinically meaningful performance for both approaches. Qualitative assessment based on expert visual inspection of predicted bounding boxes revealed complementary strengths: (Pretrained + GSch + 4FExL) exhibited higher recall for subtle or infrequent findings, whereas (Pretrained + FPRbl) produced cleaner bounding boxes with higher-confidence predictions. Conclusions: This study presents how targeted architectural refinements in YOLOv8-OBB can enhance the detection of small, low-contrast, and variably oriented ultrastructural features in renal TEM images. Evaluating these refinements and translating them into a web-based platform (Renal-AI) showed the clinical applicability of deep learning-based tools for improving diagnostic efficiency and reducing interpretive variability in kidney pathology. Full article

Background and Clinical Significance: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis that often affects the respiratory tract and kidneys, while ocular involvement is less common and may delay diagnosis. Bilateral dacryoadenitis as an initial manifestation is particularly uncommon and can obscure early recognition. Case Presentation: A 24-year-old woman presented with recurrent epistaxis, headaches, and progressive bilateral eyelid swelling. MRI showed enlarged lacrimal glands consistent with granulomatous dacryoadenitis. Over the following weeks, she developed systemic symptoms and rapidly progressive renal impairment. Serology revealed positive c-ANCA and anti-PR3 antibodies, and HRCT demonstrated pulmonary nodules and ground-glass opacities. Renal biopsy confirmed necrotizing pauci-immune crescentic glomerulonephritis. Despite treatment with glucocorticoids, cyclophosphamide, and rituximab, renal recovery was incomplete, necessitating hemodialysis. Conclusions: This case illustrates bilateral dacryoadenitis as an early sign of GPA and emphasizes the need for prompt ANCA testing and renal evaluation. Early recognition is crucial to prevent irreversible kidney damage. Full article

Evaluating the activity of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan (Trp) metabolism, is important because IDO is involved in immune tolerance and drives the production of Trp metabolites implicated in psychiatric disorders and cancer. This study aimed to design and develop a novel fluorescent l-Trp derivative to fluorometrically monitor Trp-catabolizing enzyme activity via IDO. To evaluate IDO activity in vivo, 7-N,N-dimethylamino-2,1,3-benzoxadiazole (DBD), a fluorophore, was covalently bound at the 5-position of the indole ring in Trp to produce 5-DBD-l-Trp. An in vivo microdialysis (MD) study was conducted using the kidneys of Sprague–Dawley rats. Specifically, 5.0 μM 5-DBD-l-Trp in phosphate-buffered Ringer’s solution was infused into the rats, and the MD sample was analyzed via high-performance liquid chromatography with fluorescence detection. In the MD sample, two fluorescence peaks other than 5-DBD-l-Trp were observed during the 5-DBD-l-Trp infusion, and the main metabolite peak was proposed to be 5-DBD-kynurenine, verified by liquid chromatography-tandem mass spectrometry. The intensity of the fluorescent peak was significantly attenuated by co-infusion with an IDO inhibitor, 1-methyl-d-Trp. These results suggest that 5-DBD-l-Trp may be metabolized by renal IDO and can be used to evaluate IDO activity in vivo. Full article

Introduction: Temporary non-tunneled catheters are necessary in patients with chronic kidney disease requiring acute hemodialysis care, and complications associated with these catheters, such as infection and thrombosis, represent the most important sources of morbidity. There are no studies available that suggest the optimum duration of their use before catheter exchange or removal. This study aimed to explore the duration of temporary catheter insertion before the occurrence of catheter-related infection and mechanical complications in hemodialysis patients. Methods: Systematic searches were conducted according to the PRISMA 2020 guidelines on four databases up to 1 May 2025 (PROSPERO: CRD420251069657). The study outcome was the occurrence time to catheter-related infection and mechanical complications (thrombosis, obstruction, and kinking, causing dysfunction, failure, or insufficient blood flow) in days, pooled using a single-arm meta-analysis. Mean and 95% confidence interval (CI) were used as the summary statistics. Results: Nine studies involving 1448 participants undergoing hemodialysis using temporary catheters were included. Incidence of infection ranged from 0.7 to 13.58 per 1000 catheter-days. The most common bacterium identified was Staphylococcus aureus and Pseudomonas aeruginosa. The pooled mean time to catheter-related infection from 298 catheters was 15.98 days (95% CI 10.47–21.50; I² = 97.73%). We also found that the pooled mean time to mechanical complications from 507 catheters was 6.69 days (95% CI 2.49–10.90; I² = 98.03%). Conclusion: Among patients who developed complications, the mean time from temporary catheter insertion was approximately two weeks to the occurrence of catheter-related infection and one week to mechanical complications. Our finding was consistent with the recommendation of the KDOQI guideline, which suggests limiting catheter duration to typically less than two weeks. Full article

Background: As a widely used chemotherapeutic agent, cisplatin frequently induces acute kidney injury (AKI), which severely compromises patient survival and limits its clinical use. While the natural flavonoid diosmetin (Dio) shows promise in mitigating cisplatin-induced nephrotoxicity, its clinical translation is challenged by poor solubility, low bioavailability, and incompletely elucidated mechanisms. This study aimed to overcome these limitations by developing a novel drug delivery system using the microalgae Dunaliella salina (D. salina, Ds) to load Dio (Ds-Dio), thereby enhancing its efficacy and exploring its therapeutic potential. Methods: We first characterized the physicochemical properties of Ds and Dio, and then Ds-Dio complex was synthesized via co-incubation. Its nephroprotective efficacy and safety were systematically evaluated in a cisplatin-induced mouse AKI model by assessing renal function (serum creatinine, blood urea nitrogen), injury biomarkers, histopathology, body weight, and organ index. The underlying mechanism was predicted by network pharmacology and subsequently validated experimentally. Results: The novel Ds-Dio delivery system has been successfully established. In the AKI model, Ds-Dio significantly improved renal function and exhibited a superior protective effect over Dio alone; this benefit is attributed to the enhanced bioavailability provided by Ds carrier. In addition, Ds-Dio also demonstrated safety performance, with no evidence of toxicity to major organs. Network pharmacology analysis predicted the involvement of PI3K/AKT pathway, which was experimentally verified. Specifically, we confirmed that Ds-Dio alleviates AKI by modulating the PI3K/AKT pathway, resulting in concurrent suppression of NF-κB-mediated inflammation and activation of NRF2-dependent antioxidant responses. Conclusions: This study successfully developed a microalgae-based drug delivery system, Ds-Dio, which significantly enhances the nephroprotective efficacy of Dio against cisplatin-induced AKI. The nephroprotective mechanism is associated with modulation of the PI3K/AKT pathway, resulting in the simultaneous attenuation of oxidative stress and inflammation. Full article

RNA viruses are major pathogens in fish, causing high mortality and substantial economic losses in aquaculture. To uncover conserved antiviral mechanisms, we investigated the response of turbot (Scophthalmus maximus) to viral hemorrhagic septicemia virus (VHSV), infectious pancreatic necrosis virus (IPNV), and red-spotted grouper nervous necrosis virus (RGNNV) using a comparative proteomic approach complemented by in vivo and in vitro functional assays. Proteomic analyses revealed the central, conserved role of proteins involved in reactive oxygen species (ROS) production and redox homeostasis during early infection. Functional assays using head kidney-derived leukocytes identified neutrophils and macrophages as the primary ROS producers and showed that the modulation of cytoplasmic and mitochondrial ROS, as well as ROS-dependent DNA release, follows virus-specific patterns. The pharmacological inhibition of NADPH oxidase and mitochondrial ROS significantly affected viral replication, demonstrating the direct role of ROS in viral pathogenicity. Collectively, these findings highlight redox modulation as a conserved host response in teleost fish during RNA virus infection, linking oxidative stress regulation to viral progression. This knowledge provides a foundation for developing broad-spectrum therapeutic or preventive strategies to enhance disease resistance and promote sustainable aquaculture. Full article

Background: Diabetic nephropathy (DN) is largely driven by transforming growth factor-β1 (TGF-β1)-mediated fibrosis. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes offer precise gene disruption, yet effective non-viral delivery remains a challenge. This study developed cationic lipid-based hybrid nanostructured lipid carriers (NLCs) for intracellular delivery of TGFB1-targeting RNP as an early-stage platform for DN gene modulation. Methods: A single-guide RNA (sgRNA) targeting human TGFB1 was assembled with Cas9 protein (1:1 and 1:2 molar ratios). Hybrid NLCs comprising squalene, glyceryl trimyristate, and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were formulated via optimized emulsification–sonication to achieve sub-100 nm particles. Physicochemical properties, including polydispersity index (PDI), were assessed via dynamic light scattering (DLS), while silencing efficacy in HEK293T cells was quantified using quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: Optimized NLCs achieved hydrodynamic diameters of 65–99 nm (PDI < 0.5) with successful RNP complexation. The 1:2 Cas9:sgRNA formulation produced the strongest gene-editing response, reducing TGFB1 mRNA by 67% (p < 0.01) compared with 39% for the 1:1 ratio. This translated to a significant reduction in TGF-β1 protein (p < 0.05) within 24 h. Conclusions: DOTAP-based hybrid NLCs enable efficient delivery of CRISPR–Cas9 RNP and achieve significant suppression of TGFB1 expression at both transcriptional and protein levels. These findings establish a promising non-viral platform for upstream modulation of profibrotic signaling in DN and support further evaluation in kidney-derived cells and in vivo renal models. Full article

Systemic lupus erythematosus (SLE) is a chronic and refractory autoimmune disease characterized by multi-organ damage, for which reliably safe and effective treatment remains an unmet need. Autoantibodies, secreted by autoreactive B cells, deposition is the central pathogenesis of organ damage in SLE. Current studies reported B cell receptor and B cell activating factor (BAFF)-mediated signals regulate the activation and survival of B cells and production of autoantibodies. We showed that marginal zone B cells and CD11c⁺T-bet⁺ autoreactive B cells expressed higher levels of BAFF receptor and BTK in MRL/lpr mice. Here, a liposome-delivery system capable of targeting BAFFR^high autoreactive B cells by conjugating anti-BAFFR antibody on the surface of the PEG-liposomes and loading BTK-inhibitor ibrutinib (BTEL) was rationally designed. Notably, the BTEL nanoparticles could inhibit the survival and activation of B cells, and systemic administration of BTEL could alleviate the development of the lupus mouse model by decreasing the production of anti-dsDNA autoantibodies, along with reduced secretion of inflammatory cytokines and kidney damage, and without apparent side effects. These findings suggest the potential of BTEL in targeting autoreactive B cells, blocking signaling pathways, and improving the efficacy of BTK inhibitors, providing a promising therapeutic approach for SLE, while also reducing toxicity. Full article

Diabetic wounds exhibit impaired immune function, delayed neutrophils recruitment, and heightened infection risk which compromises early infection control and delays healing. We have demonstrated that topical CCL3 treatment restores neutrophil influx, reduces bacterial infection by ~99%, and accelerates wound healing in diabetic mice. As per Food and Drug Administration (FDA) Guidelines for Investigational New Drug (IND), we conducted a 14-day acute toxicity study in diabetic mice following a single topical administration of CCL3 at effective low dose (1 µg) and high dose (10 µg) per wound. Mice were monitored for clinical signs, body weight, and food intake throughout the study period. On day 14, serum biochemistry (ALT, AST, BUN, creatinine, metabolic markers) and histopathology of major organs (liver, kidney, heart, lungs, spleen) were assessed. CCL3-treated diabetic mice exhibited no adverse clinical effects. Hematological and biochemical parameters remained within normal limits, and histopathological analyses revealed no additional organ injury in CCL3-treated groups compared to diabetic control mice. Intriguingly, CCL3-treated mice showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced serum IgG, indicating reduced systemic inflammation. Overall, our study demonstrates that diabetic mice tolerate topical CCL3 at doses up to 10 times the effective therapeutic concentration without evidence of systemic organ toxicity. These findings provide strong preclinical support for the translational development of CCL3 as a novel therapy for diabetic wound care. Full article

Hyperkalemia is a major complication of chronic kidney disease (CKD). However, owing to the absence of specific symptoms in its early stages, hyperkalemia frequently remains undiagnosed. This study aimed to develop a machine learning model for predicting the risk of early hyperkalemia in patients with CKD. By conducting a comparative analysis of six machine learning methods, CatBoost demonstrated superiority across various evaluation metrics. Further evaluation using confusion matrix and decision curve analysis (DCA) confirmed its high classification accuracy and substantial clinical utility. Meanwhile, through multiple interpretability analyses based on SHAP and Local Interpretable Model-agnostic Explanations (LIME) techniques, we precisely quantify the contributions and positive or negative effects of risk factors for hyperkalemia. Full article

Obstructive uropathy (OU) during fetal development induces a fetal cystic dysplastic kidney. The mechanisms of cyst formation and the onset of renal dysfunction remain unclear. Determining whether nephrogenic potential persists during fetal life may suggest whether early intervention could preserve renal development. We aimed to evaluate residual nephrogenic activity in fetal cystic dysplastic kidneys using β-catenin and CD10 immunostaining, and to assess whether the site of obstruction influences cystogenesis. After appropriate approval, 20 timed-gestation fetal lambs had OU created at 60 days. Males underwent urethral and urachal ligation (n = 8, 3 lost), and females underwent unilateral ureteric ligation (n = 8, 1 lost). Fetuses were sacrificed at 80 days (n = 6) and 140 days (term, n = 10), comparing kidneys with normal controls of the same gestational age using immunohistochemical staining for β-catenin and CD10. Developing fetal cystic dysplastic kidneys were identified at 80 days. β-catenin staining showed the absence of granular cytoplasmic expression in cystic regions, indicating arrested nephrogenesis. In male models, cysts originated exclusively from proximal tubules. Female models exhibited mixed proximal and distal tubular involvement. CD10 staining confirmed the loss of proximal tubular markers. Renal development remained arrested at term. Cyst formation disrupts renal development early in gestation, which persists until term. Differences in cystogenesis between the models suggest that the site of obstruction influences pathogenic mechanisms. Full article

Background/Objectives: Uremic pruritus is a common complication in patients with end-stage kidney disease undergoing maintenance hemodialysis. Despite its high prevalence and substantial impact on sleep, psychological well-being, and overall quality of life, its pathophysiology remains multifactorial and incompletely understood. This narrative review summarizes contemporary evidence (2015–2025) on therapeutic strategies for uremic pruritus, with an emphasis on emerging treatments and evolving mechanistic insights. Methods: A PubMed search was conducted for original clinical studies published between 1 January 2015, and 31 October 2025, evaluating treatments for uremic pruritus in adult hemodialysis patients. Eligible study designs included randomized controlled trials and observational interventional studies. Non-English articles, pediatric studies, peritoneal dialysis studies, reviews, case reports, and studies of mixed-etiology pruritus were excluded. Earlier literature was reviewed to contextualize epidemiology and pathophysiology. Results: The review identifies multiple interacting mechanisms—including uremic toxins, immune dysregulation, mineral abnormalities, xerosis, neuropathic changes, and dysregulated opioid signaling—contributing to itch generation. Topical therapies, especially emollients and humectants, consistently improved symptoms with excellent safety profiles. Optimization of dialysis adequacy and membrane selection showed benefit in selected patients. Among systemic therapies, gabapentinoids demonstrated the most robust efficacy but required cautious dosing. Sertraline, nalbuphine, and difelikefalin showed significant antipruritic effects in controlled trials. Emerging therapies, including AST-120, omega-3 fatty acids, and the biologic dupilumab, demonstrated promising but preliminary results. Conclusions: Management of uremic pruritus requires a multifaceted, individualized approach integrating skin-directed therapies, dialysis optimization, and targeted systemic treatments. Ongoing research is needed to identify reliable biomarkers and to develop safer, more effective, mechanism-based therapies. Full article