Search Results (20,982)

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease and end-stage renal disease worldwide and results from the long-term effects of hypertension on renal structure and function. The pathogenesis of HN is complex and involves haemodynamic disturbances, renal vascular injury, oxidative stress, chronic inflammation, and progressive interstitial fibrosis. In recent years, increasing attention has focused on the role of non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—as key regulators of gene expression involved in these processes. This review summarises the current understanding of the molecular mechanisms underlying HN, with particular emphasis on the roles of oxidative stress, activation of the renin–angiotensin–aldosterone system, transforming growth factor beta signalling, and inflammatory and fibrogenic pathways. The contribution of dysregulated ncRNAs to endothelial dysfunction, inflammatory responses, apoptosis, angiogenesis, and renal remodelling and fibrosis is also discussed. Particular attention is given to miRNAs and lncRNAs as mediators of disease progression and potential biomarkers, as well as to the emerging role of circRNAs in hypertensive kidney injury, including their involvement in the regulation of redox balance and intercellular communication. Collectively, available evidence indicates that ncRNAs represent a critical link between haemodynamic stimuli and persistent molecular alterations in renal tissue, highlighting their potential as diagnostic markers and therapeutic targets in HN. Full article

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications. Full article

Background/Objectives: The corneal endothelium maintains corneal transparency through its barrier function and active pumping mechanism that regulates stromal hydration. Limited regenerative capacity makes these cells vulnerable to progressive cell loss. Although local ocular factors are well known, recent data suggest that numerous systemic diseases may contribute to endothelial dysfunction and reduce endothelial reserve before the onset of clinically apparent corneal pathology. The purpose of this narrative review is to synthesize current evidence on the impact of systemic diseases on corneal endothelial health and to highlight the underlying mechanisms and clinical implications. Methods: A narrative literature review was conducted using the PubMed, MEDLINE, and Google Scholar databases for articles published between January 2000 and December 2025. Observational studies, case series, and review articles that evaluated structural or functional changes in the corneal endothelium in association with systemic diseases were included. Results: Reviewed literature shows that several categories of systemic diseases are associated with signs of corneal endothelial stress. These changes include decreased endothelial cell density, increased cell size variability, reduced hexagonality, and, in some cases, increased central corneal thickness. Metabolic, cardiovascular, renal, autoimmune, and hypoxic conditions, as well as extracellular matrix disorders and aging, show consistent associations with these changes. Conclusions: Systemic diseases can compromise corneal endothelial integrity and reduce functional reserve even in the absence of clinically evident corneal pathology. Recognition of these associations underscores the importance of evaluating the patient’s systemic context, including a detailed medical history and corneal endothelial analysis, particularly before intraocular surgery. Full article

Background: Organic cation transporter 2 (OCT2) mediates the renal uptake of cisplatin and is a principal contributor to its dose-limiting nephrotoxicity. Despite reports of OCT2 inhibition by various phytochemicals, the structure–activity relationships (SARs) governing inhibition and their functional implications remain poorly understood. Methods: We systematically evaluated OCT2 inhibitory activity across a structurally diverse library of 146 phytochemicals, including anthraquinones, flavanols, stilbenes, and isoflavones, using Madin–Darby canine kidney (MDCK) cells stably overexpressing OCT2. Structure–activity relationships were analyzed using non-parametric statistics and multivariate logistic regression, and functional relevance was assessed via cisplatin-induced cytotoxicity assays. Results: Inhibitory activity varied widely across the library, with potent inhibitors identified across multiple chemical scaffolds. Non-parametric statistical analyses revealed no significant differences in overall activity distributions among scaffold classes. Notably, chemical substituent patterns, rather than core scaffold identity, were the primary drivers of OCT2 inhibitory potency. Methoxylation was consistently associated with enhanced OCT2 inhibition, particularly within isoflavones, although its impact varied across structural scaffolds. The selected OCT2 inhibitors markedly reduced cisplatin-mediated cell death in OCT2-expressing cells but not in mock-transfected controls, confirming an OCT2-dependent mechanism of protection. Conclusions: This study establishes a structure-guided framework linking phytochemical OCT2 inhibition to nephroprotective potential and identifies methoxylation as a major determinant of OCT2-targeted intervention strategies. Full article

Background/Objectives: Growing evidence indicates that melatonin contributes to kidney development and function, while disruptions of fetal circadian signaling have been linked to congenital anomalies of the kidney and urinary tract (CAKUT). This study aimed to characterize the developmental and spatial expression patterns of melatonin receptors MTNR1A and MTNR1B in normal human fetal kidneys and in CAKUT phenotypes. Methods: This study analyzed 40 human fetal kidney specimens, including healthy controls and CAKUT cases (horseshoe kidneys, duplex kidneys, and dysplastic kidneys), obtained from spontaneous abortions and pregnancy terminations. Samples were classified into developmental phases Ph2–Ph4 according to established morphological criteria. Immunofluorescence staining was used to visualize MTNR1A and MTNR1B expression. Quantitative analysis was performed using ImageJ, measuring the fluorescence area percentage. Statistical comparisons were conducted using a two-way ANOVA. Results: In control kidneys, MTNR1A expression was predominantly observed in glomeruli and interstitial cells and showed a descending trend across developmental stages, whereas MTNR1B was localized to glomeruli and strongly to the apical membranes of tubules, particularly distal tubules, without substantial developmental variation. CAKUT phenotypes exhibited higher expression of both receptors compared to controls. Significant phase-dependent differences in MTNR1A expression were observed in horseshoe, duplex, and dysplastic kidneys. MTNR1B expression decreased across developmental stages in dysplastic kidneys and differed significantly between Ph3 and Ph4 in duplex kidneys. At Ph3, duplex kidneys showed the highest MTNR1B expression. Conclusions: Altered developmental expression patterns of MTNR1A and MTNR1B in CAKUT suggest an association between melatonin signaling and abnormal human kidney development. Full article

Introduction: Acquired ureteral stricture is an uncommon but clinically relevant complication, mainly associated with long-standing urolithiasis, chronic inflammatory processes, and repeated endourological procedures. Case presentation: We present the case of a 48-year-old woman with left distal ureteral stricture secondary to urolithiasis and repeated endourological procedures, with a complicated clinical course and progressive renal functional impairment. Despite stepwise management including balloon dilations, endoscopic incision, prolonged urinary diversion, and ultimately ureteral reimplantation with a psoas hitch, the patient developed restenosis of the ureteral neomeatus. Due to persistent obstruction, endoscopic dilation with a paclitaxel-coated balloon (Optilume^®) was performed. Subsequent imaging demonstrated partial improvement in ureteral drainage and relative functional improvement of the left kidney. Conclusion: This case highlights the potential complementary role of drug-coated balloons in complex and refractory benign ureteral strictures, although the currently available evidence remains limited. Full article

Background: Early postoperative changes in creatinine-based estimated glomerular filtration rate (eGFR) after bariatric surgery can be misread as a kidney injury. During rapid weight loss, indexing eGFR to a fixed body surface area (BSA) of 1.73 m² may alter apparent trajectories. We compared absolute (mL/min) and BSA-indexed (mL/min/1.73 m²) eGFR changes after sleeve gastrectomy, stratified by baseline glomerular hyperfiltration (GH). Methods: In this retrospective cohort of 145 adults undergoing laparoscopic sleeve gastrectomy, serum creatinine was obtained at baseline (≤30 days pre-op) and 3 months (post-op days 75–105). Indexed eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 creatinine equation; BSA with the Mosteller formula; and absolute eGFR as indexed eGFR × (BSA/1.73). GH was defined as indexed eGFR ≥ 120 mL/min/1.73 m². A REML mixed-effects model (Group, Time, Group × Time) with patient-cluster bootstrap inference was used. An age-adjusted sensitivity model including Age and Age × Time was also fitted. Results: Fifty-four participants (37%) met the GH criteria. Absolute eGFR declined by −26.6 mL/min in GH versus −17.3 mL/min in non-GH (difference-in-differences [DiD] −9.3 mL/min; 95% CI −13.9 to −4.7; p < 0.001). The indexed eGFR changes were smaller (−4.2 vs. −0.5 mL/min/1.73 m²; DiD −3.7; 95% CI −7.3 to −0.03; p = 0.048; bootstrap p_sign = 0.052). In the age-adjusted sensitivity model, the Group × Time interaction for absolute eGFR attenuated but remained statistically significant (−6.57 mL/min; 95% CI, −13.09 to −0.06; p = 0.048), whereas the corresponding interaction for indexed eGFR was attenuated and no longer statistically significant (−3.99 mL/min/1.73 m²; 95% CI −9.15 to 1.16; p = 0.129). Conclusions: Within three months after sleeve gastrectomy, participants with higher baseline indexed filtration showed a larger decline in absolute eGFR but only a small change in indexed eGFR. These results show that early postoperative creatinine-based eGFR trajectories are scale dependent and should be interpreted cautiously during rapid weight loss. Because postoperative acute kidney injury (AKI) was not adjudicated and direct kidney function markers were unavailable, this study does not distinguish physiological hemodynamic change from structural kidney injury. Reporting both absolute and indexed eGFR may improve early postoperative interpretation and help align dosing decisions with rapid changes in body size. Full article

Background/Objectives: Acute-on-chronic liver failure (ACLF) is a severe syndrome in chronic liver disease (CLD) patients, characterized by multi-organ failure and high mortality. Living donor liver transplantation (LDLT) is vital in donor-scarce areas. This study compares baseline characteristics, perioperative complications, and long-term survival between ACLF and non-ACLF patients, emphasizing etiology, ACLF grading, and graft factors. Methods: Data from a prospective registry of 591 adult LDLT recipients (2019–2023) were analyzed. ACLF was defined by EASL-CLIF (multi-organ failure, grades 1–3) and APASL (jaundice/coagulopathy with complications) criteria, evaluated at initial assessment and within 24 h pre-LDLT. Results: ACLF patients (n = 101, 17.1%) showed higher MELD-Na (27 vs. 20, p < 0.001), bilirubin (6.84 vs. 1.75 mg/dL, p < 0.001), creatinine (108 vs. 70.5 μmol/L, p < 0.001), metabolic/genetic etiologies (9.9% vs. 2.8%, p = 0.001), and chronic kidney disease (23.7% vs. 8.1%, p < 0.001), and lower HCC rates (11.8% vs. 29.6%, p < 0.001). GRWR was marginally lower in ACLF patients (0.59 vs. 0.66, p = 0.10). The ACLF group had elevated infection (27.7% vs. 10.4%, p < 0.001), bleeding (14.9% vs. 6.3%, p = 0.004), and biliary complications (15.8% vs. 7.8%, p = 0.010), with longer ICU (5 vs. 3 days, p < 0.001) and hospital stays (33.66 vs. 20.7 days, p = 0.036). Five-year overall survival was reduced in ACLF patients (log-rank p = 0.001), worsening with grade (EASL-CLIF grade 3: 55% vs. 81% for no ACLF, p = 0.002). Graft survival was also lower (75% vs. 85%, p = 0.02). Multivariable analysis identified chronic kidney disease as an independent mortality predictor (HR 2.09, 95% CI 1.11–3.95, p = 0.023). Conclusions: LDLT for ACLF involves higher perioperative risks and poorer long-term survival than non-ACLF patients, with outcomes deteriorating by ACLF grade. Chronic kidney disease independently predicts mortality. Timely LDLT is essential in donor-limited regions. Full article

Acute kidney injury (AKI) presents a critical clinical challenge due to its rapid progression and lack of effective targeted therapies. The herbal combination of rhubarb and Salvia miltiorrhiza, a cornerstone of Traditional Chinese Medicine (TCM) for renal protection, shows promise, yet its bioactive components and mode of action remain incompletely understood. This study identifies and characterizes inherent nanoscale entities from this herbal pair as a novel nanotherapeutic platform. Self-assembled nanoparticles (designated RSNPs) were isolated from the ethanol extract via differential centrifugation. Comprehensive characterization revealed that RSNPs form stable nanostructures through spontaneous self-assembly, primarily driven by supramolecular interactions (e.g., π-π stacking and hydrogen bonding). UPLC-MS/MS quantification confirmed the co-assembly of multiple bioactive constituents within RSNPs. Network pharmacology and molecular docking initially predicted their synergistic action on AKI-related pathways. In a cisplatin-induced murine AKI model, RSNP administration markedly attenuated renal dysfunction and histopathological damage, mechanistically linked to the mitigation of oxidative stress (e.g., decreased MDA and increased SOD) and inflammation (e.g., downregulated TNF-α and IL-6). In vitro, RSNPs demonstrated enhanced cellular internalization and superior cytoprotection against cisplatin toxicity in renal tubular epithelial cells, significantly reducing apoptosis. These findings unveil that the therapeutic efficacy of the Rheum palmatum L.–Salvia miltiorrhiza Bunge pair is intrinsically embedded within its nanoscale architecture. RSNPs represent a new class of TCM-derived nanotherapeutics with a well-defined material basis and multimodal mechanisms, offering a promising strategy for AKI treatment. Full article

Chronic kidney disease is rising worldwide, and kidney transplantation remains the preferred modality of kidney replacement therapy. However, long-term graft survival continues to be limited by chronic alloimmune injury, particularly antibody-mediated rejection (ABMR) and its chronic active form. This narrative review synthesizes contemporary evidence on the immunopathogenesis, epidemiology, diagnosis, and management of kidney allograft rejection, with a deliberate focus on studies from the last five years and on United States and European cohorts. We summarize current concepts of T cell–mediated rejection (TCMR), ABMR, mixed and donor-specific antibody (DSA)–negative phenotypes, and the evolution of the Banff classification, highlighting how chronic active ABMR has emerged as a leading cause of death-censored graft loss. We then critically appraise the conventional diagnostic triad of creatinine/eGFR, DSA, and biopsy and review emerging tools, including donor-derived cell-free DNA, urinary chemokines such as CXCL9 and CXCL10, additional blood- and urine-based biomarkers, and biopsy transcriptomics. We also examine how artificial intelligence and machine learning may support digital pathology, multimodal risk prediction, and data integration, while recognizing the current challenges of biological interpretability, external validation, and clinical implementation. Finally, we propose a rejection-focused precision-medicine framework and outline key research gaps, including multicenter validation, trial-ready endpoints, and governance for AI-enabled pathways. Overall, the field is moving from isolated diagnostic signals toward integrated, biologically informed, and clinically actionable approaches to rejection detection and risk stratification. Full article

Metabolic dysfunction-associated (non-alcoholic) steatotic liver disease (MASLD) is a chronic inflammatory liver disorder characterized by excessive hepatic lipid accumulation. Its progressive subtype, metabolic dysfunction-associated (non-alcoholic) steatohepatitis (MASH), is featured by enhanced inflammation and liver injury. Some MASH cases are accompanied by hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). MASLD is also associated with comorbidities such as cardiovascular disease and chronic kidney disease. To date, only Resmetirom has been approved by the FDA for MASH treatment, highlighting the urgency of investigating MASH pathogenesis and developing effective therapeutic agents. Establishment of experimental animal models which can mimic the clinical symptom of MASLD are fundamental to explore therapeutic targets and advance clinical drugs development. Therefore, this review focus on the pathological features of MASLD/MASH and comprehensively summarizes the current MASH-related mouse models, which can be useful for researchers to select appropriate models in order to explore the underlying mechanisms and dig novel targets for MASH treatment. Full article

Background and Objectives: This study investigated the prognostic value of the C-reactive protein–albumin–lymphocyte (CALLY) index in predicting all-cause mortality among patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. Materials and methods: This retrospective single-center study included 303 patients who underwent TAVI. The CALLY index and other established prognostic scores were calculated at baseline. Patients were followed for a median of 21 months. The primary endpoint was all-cause mortality. Results: A total of 60 patients (19.8%) died during follow-up. The CALLY index demonstrated the highest predictive performance for all-cause mortality, with an AUC of 0.698 (95% CI: 0.628–0.768, p < 0.001). In multivariate Cox regression, a low CALLY index remained an independent predictor of mortality (HR: 3.80, 95% CI: 2.03–7.11, p < 0.001), along with reduced LVEF, chronic kidney disease, and diabetes mellitus. Kaplan–Meier analysis further confirmed markedly worse survival in the high-risk group (log-rank p < 0.001). Conclusions: The CALLY index was independently associated with mortality after TAVI and may represent a complementary biomarker for risk stratification in this population. Full article

Renal surgery for localized renal cell carcinoma carries substantial risk of acute kidney injury (AKI) regardless of surgical approach. This prospective study evaluated early biohumoral markers for AKI detection after robotic renal surgery and assessed their prognostic value for 12-month functional outcomes. Adults undergoing robotic renal tumor surgery with a healthy contralateral kidney were enrolled; AKI followed KDIGO 2012 criteria. Biomarkers measured at baseline and 2/24/72 h were serum β2-microglobulin (sβ2) serum IL-6, as well as urinary β2-microglobulin (uβ2), cystatin C (uC), and α2-macroglobulin (uα2M). Kidney function at 12 months was staged according to KDOQI criteria. Among 170 patients (35 radical nephrectomy, RN; 135 partial nephrectomy, PN), 33 developed AKI, more frequently after RN (p < 0.001); baseline biomarkers levels were similar. sβ2 was significantly higher at 2/24/72 h, and at 2 h, it achieved an AUC of 0.78 (cut-off 0.17: sensitivity 82%, specificity 60%), remaining the earliest independent predictor of AKI (p = 0.015). IL-6 differed at 24 h (AUC 0.80), uC at 72 h (AUC 0.73) and uβ2 at 72 h (AUC 0.66). Clinical AKI predicted KDOQI stage progression at 12 months (p < 0.001). Bulldog clamps (mean ischemia time 17.2 ± 6.9 min) were not associated with AKI (p = 0.99) or with KDOQI stage progression (p = 0.54). RN confers a higher AKI risk than PN. sβ2 at 2 h is the earliest actionable marker, complemented by IL-6 (24 h) and uC (72 h); short warm ischemia during robotic PN appears safe. Sequential multimarker assessment may improve recognition of AKI and support timely nephroprotective strategies. Full article

Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects. This review consolidates current understanding of their natural and industrial sources, environmental cycling, human exposure routes, and population-level vulnerabilities. It covers their toxicokinetics and toxicodynamics, emphasizing species-specific absorption, distribution, and injury mechanisms, including oxidative stress, thiol binding, mitochondrial dysfunction, endocrine disruption, and cancer risk. Clinical signs range from subtle neurocognitive impairment and kidney damage to severe acute poisoning. The review evaluates evidence-based approaches to risk assessment and biomonitoring, such as blood, urine, hair, and speciation tests, noting issues, including unvalidated provoked testing. Treatment focuses on removing exposure, providing nutritional support, and offering supportive care, with chelation therapy reserved for specific cases. It explains the chemistry, pharmacology, and roles of chelating agents—ALA, DMSA, DMPS, Cys, GSH, and physiologic thiols, comparing their effectiveness, limitations, and costs for various metals. Emerging therapies, precision toxicology, and public health strategies are discussed within a prevention-focused context. Unlike prior reviews focused primarily on toxic mechanisms or isolated clinical management, this review integrates mechanistic toxicology, biomarker interpretation and speciation, evidence-based clinical care, and ethical, cost-conscious decision-making within a single translational framework. This narrative review synthesizes foundational and contemporary literature published through 2025, with particular emphasis on studies published since 2000 that inform toxicokinetics, biomarker interpretation, diagnostics, clinical management, and prevention. Full article

Background: Kidney transplantation (KT) improves survival and quality of life in patients with end-stage kidney disease; however, long-term allograft survival remains a major challenge. Brain natriuretic peptide (BNP), a biomarker of cardiorenal stress and volume status, may be associated with early postoperative physiological changes after KT. This study evaluated the association between early postoperative BNP changes and long-term allograft survival, and explored the potential role of BNP-derived parameters in relation to graft outcomes. Methods: This retrospective cohort study included adult recipients of deceased-donor KT between 2009 and 2018. Patients were categorized according to early graft function. Serum BNP levels were measured preoperatively and within postoperative 24 h, and the percentage increase (dBNP ratio) was calculated. Cox regression and receiver operating characteristic analyses were used to identify risk factors for graft failure and evaluate the discriminatory performance of BNP-derived biomarkers, respectively. Results: Among the 179 recipients, postoperative BNP levels and dBNP ratios differed significantly across graft function groups, with higher values in delayed graft function. After multivariate adjustment, the dBNP ratio remained significantly associated with graft failure (hazard ratio, 1.16; 95% confidence interval, 1.10–1.21; p < 0.001). Additionally, the dBNP ratio demonstrated better discriminatory performance for graft failure compared with postoperative BNP alone (area under the curve, 0.815 vs. 0.596; p < 0.001), with an exploratory cutoff of approximately 18%. Recipients with a dBNP ratio ≥ 18% had poorer early graft function, lower longitudinal estimated glomerular filtration rates, and significantly reduced graft survival. Conclusions: An increased early postoperative dBNP ratio was significantly associated with adverse long-term kidney allograft outcomes. However, given the potential for residual confounding, these findings should be interpreted as associative and hypothesis-generating rather than predictive. Full article