Search Results (1,097)

Diabetes mellitus currently represents a major public health burden worldwide. Among diabetic individuals, diabetic nephropathy (DN) is a frequent and serious microvascular complication that markedly affects both patients’ quality of life and clinical outcomes. DN has also emerged as the leading contributor to end-stage renal disease (ESRD). Over recent years, the stimulator of interferon genes (STING) signaling pathway (an essential element of the innate immune system) has drawn substantial research interest because of its involvement in inflammation and cell injury. This article reviews the fundamental mechanisms of the STING pathway and its regulatory functions in the pathogenesis of DN, with a focus on how the STING pathway mediates inflammatory responses, apoptosis, and fibrosis in diabetic renal tissues. Additionally, combining the latest findings from preclinical and clinical research, we discuss potential therapeutic strategies targeting the STING pathway. Beyond traditional STING inhibitor therapies, we highlight the emerging field of precision medicine for DN, summarizing recent research achievements in gene intervention, such as CRISPR-based gene editing, RNA interference (RNAi) technologies, and combination therapy strategies. Distinct from prior reviews, this work discusses the emerging concept that STING may function as a molecular hub connecting inflammation, fibrosis, and cell death in DN, while emphasizing that this concept is mainly supported by preclinical and early human observational evidence. Through this comprehensive review, we aim to enhance our understanding of the role of the STING signaling pathway in DN, identify novel therapeutic targets, and provide theoretical perspectives for the prevention and treatment strategies that require further clinical validation. Full article

Chronic kidney disease (CKD) is associated with a high burden of cardiovascular morbidity and mortality, while lipid disorders in renal failure differ substantially from the LDL-C-centered pattern observed in the general population. This narrative review aimed to synthesize recent evidence on the mechanisms, clinical implications, and therapeutic management of dyslipidemia in patients with renal failure, with emphasis on cardiovascular events and CKD progression. A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for publications from January 2018 to April 2026. The review shows that CKD-related dyslipidemia is characterized by triglyceride-rich lipoprotein and remnant particle accumulation, small dense and modified LDL, and dysfunctional HDL within a uremic-inflammatory environment that promotes endothelial injury, vascular calcification, and residual cardiovascular risk. These abnormalities may also contribute to renal lipotoxicity, proteinuria, glomerulosclerosis, tubulointerstitial injury, and fibrosis, although direct causal and therapeutic implications remain incompletely established. Statin-based therapy remains central in non-dialysis CKD, whereas lipid management in dialysis, transplantation, frailty, and severe hypertriglyceridemia requires individualized interpretation. Future risk assessment should integrate lipid, inflammatory, vascular, nutritional, and renal-trajectory markers rather than relying on LDL-C alone. Full article

Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg/dL, estimated glomerular filtration rate of 16 mL/min/1.73 m², and proteinuria of 2874 mg/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease. Full article

The kidney is a highly specialized organ that maintains systemic homeostasis through tightly coordinated cellular and molecular mechanisms. Renal parenchymal cells regulate metabolic waste excretion, electrolyte and acid–base balance, and blood pressure control—functions that rely on the dynamic integration of intracellular organelles. Recent advances in molecular and biochemical research have highlighted how inter-organelle communication is essential for preserving renal cell function and adaptive responses to stress. This review focuses on the molecular crosstalk among key organelles—including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and peroxisomes—primarily in tubular epithelial cells. We discuss how these interactions coordinate metabolic signaling, protein homeostasis, redox balance, and energy production and how their disruption contributes to maladaptive pathways during acute kidney injury (AKI), ultimately promoting chronic kidney disease (CKD) transition. Particular focus is placed on emerging pathways linking organelle dysfunction to inflammation, fibrosis, and metabolic reprogramming. Furthermore, we highlight recent advances in genetics and molecular therapeutics targeting organelle communication, including modulation of ER stress responses, mitochondrial biogenesis, and lysosomal function. Clinically approved agents, such as mTOR inhibitors, and experimental approaches—such as chemical chaperones and mitochondrial transplantation—demonstrate the potential to restore organelle homeostasis and mitigate renal injury. Overall, elucidating the molecular networks governing organelle crosstalk provides critical insights into kidney disease pathogenesis and identifies novel targets for therapeutic intervention in AKI-to-CKD transition. Full article

Peritoneal dialysis (PD) has long been an established modality of renal replacement therapy for patients with end-stage kidney disease (ESKD). Despite the modality’s advantages, significant inter-individual variability exists in peritoneal membrane transport characteristics, ultrafiltration capacity, and long-term technique survival. While PD therapy-related factors, such as dialysis solution composition, peritonitis episodes, and duration of therapy, contribute to these outcomes, genetic factors also play important roles in peritoneal membrane biology. Genetic studies have identified polymorphisms in genes involved in angiogenesis, inflammation, fibrosis, and endothelial function that influence PD outcomes. Variants in genes such as vascular endothelial growth factor, interleukin-6, transforming growth factor-β1, angiotensin-converting enzyme, endothelial nitric oxide synthase, and aquaporin-1 have all been reported to be associated with differences in peritoneal transport and susceptibility to membrane failure. These genetic discoveries provide significant insights into the pathways that lead to alterations in the PD membrane structure and function. This review article aims to explore current evidence on key genetic determinants of peritoneal membrane transport, inflammatory responses, and fibrotic transformation in PD, and to discuss their potential implications for personalised dialysis therapy and future research. Full article

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction is increasingly recognized as a key contributor to a broad spectrum of human diseases beyond classical cystic fibrosis (CF). CFTR is a cAMP-regulated chloride and bicarbonate ion channel expressed in both epithelial and non-epithelial tissues, where it regulates ion homeostasis, mucosal hydration, and cellular signaling. Both inherited CFTR mutations and acquired dysfunction resulting from environmental or inflammatory factors can disrupt these physiological processes and drive disease progression. Current evidence linking CFTR dysregulation to respiratory diseases, such as cystic fibrosis, chronic obstructive pulmonary disease (COPD), asthma, and HIV-associated airway disease, as well as cardiovascular, renal, neurological diseases, and cancer, is comprehensively discussed. Mechanistically, impaired CFTR function promotes oxidative stress, chronic inflammation, epithelial barrier dysfunction, altered mucociliary clearance, and dysregulation of signaling pathways, including NF-κB, TGF-β, PI3K/Akt, MAPK, and Wnt/β-catenin. In the context of HIV infection and cigarette smoke exposure, CFTR suppression is mediated in part by TGF-β signaling and miRNA-dependent mechanisms, resulting in compromised airway defense and increased susceptibility to pulmonary complications. Recent studies further demonstrate that CFTR dysregulation alters the expression of genes involved in fibrosis, inflammation, angiogenesis, and epithelial–mesenchymal transition (EMT). Notably, CFTR may act as either a tumor suppressor or a context-dependent oncogene, depending on tissue type and signaling milieu, highlighting its complex role in cancer biology. Advances in CFTR-targeted therapies, including potentiators, correctors, gene therapy, and combination approaches, have markedly improved outcomes in CF and may offer therapeutic potential for diseases associated with acquired CFTR dysfunction. We summarize the systemic consequences of CFTR dysregulation and the need for further mechanistic and translational research to clarify its role across diverse human diseases. Full article

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are traditionally considered acute and self-limited conditions. However, growing evidence suggests that recurrent or persistent UTIs may contribute to chronic kidney disease (CKD) progression through complex interactions between uropathogens and host responses. This review examines the pathophysiological links of UTIs caused by uropathogenic Escherichia coli, Klebsiella spp., and Enterococcus spp. and the development of chronic renal injury. Pathogen-specific persistence mechanisms, including intracellular survival, biofilm formation, and chronic colonization, may promote sustained inflammation, oxidative stress, and maladaptive repair responses. These processes are associated with tubular injury and progressive fibrotic remodeling. In addition, host-related factors such as diabetes, immune dysfunction, and antimicrobial resistance may further influence disease progression. Emerging biomarkers of inflammation, tubular injury, and fibrosis may improve early detection and risk stratification in patients with recurrent or complicated UTIs. Collectively, these findings support the concept that recurrent UTIs may represent potential contributors to CKD progression in susceptible individuals and highlight the importance of early recognition, pathogen-oriented management, and improved diagnostic strategies. Full article

Background/Objectives: Arsenic (ARS) exposure is a major cause of kidney injury, driven by oxidative stress, inflammation, fibrosis, and apoptosis. This study evaluated the renoprotective effects of morin (MOR) and morin-loaded PLGA nanoparticles (MOR–PGNPs) against ARS-induced nephrotoxicity in rats. Methods: Sixty male Sprague Dawley rats were randomly allocated into six groups (n = 10 per group). The control group received corn oil. The MOR group received MOR (100 mg/kg), and the MOR–PGNPs group received the same dose of MOR encapsulated in PLGA nanoparticles. ARS was administered at 10 mg/kg for 14 days. Co-treated groups received ARS together with either MOR or MOR–PGNPs, with a 28 min interval between administrations. Renal function markers (serum urea, creatinine, uric acid, renal KIM-1), oxidative stress and antioxidant parameters (Nrf2/HO-1, CAT, SOD, GPx, ROS, MDA), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-6, IL-1β), fibrotic markers (TGF-β1, fibronectin), and apoptotic proteins (caspase-3, caspase-8, Bax, Bcl-2) were assessed, alongside histopathological and ultrastructural evaluations. Results: ARS exposure significantly impaired renal function, increased KIM-1, suppressed Nrf2/HO-1 signaling, reduced antioxidant enzyme activities, and elevated ROS and MDA levels. It also activated TLR4/NF-κB signaling, upregulated pro-inflammatory cytokines and fibrotic markers, and increased pro-apoptotic proteins while downregulating Bcl-2. MOR co-treatment partially ameliorated these alterations. MOR–PGNPs produced potentially enhanced protection, restoring kidney function markers, enhancing antioxidant defenses, and markedly attenuating inflammation, fibrosis, and apoptosis. Histopathological and ultrastructural analyses confirmed preservation of glomerular and tubular architecture, mitochondrial integrity, and minimal cytoplasmic vacuolization in the MOR–PGNPs group. Conclusions: MOR–PGNPs at 100 mg/kg effectively mitigated ARS-induced renal damage through antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic mechanisms, supporting PLGA-based morin nanoparticles as a promising and safe renoprotective strategy. Full article

Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Conventional clinical markers of renal function lack sufficient sensitivity for early diagnosis, whereas renal biopsy is unsuitable for routine monitoring because of its invasiveness. Objective: This narrative review aimed to evaluate recent advances in novel, non-invasive multimodal magnetic resonance imaging (MRI) biomarkers for the assessment of renal pathological alterations in DKD. Recent findings: Recent studies have demonstrated that multimodal MRI can non-invasively characterize several key pathological features of DKD, including renal hypoxia, microvascular dysfunction, ectopic fat deposition, and interstitial fibrosis. Furthermore, emerging evidence suggests that these imaging biomarkers may enhance risk stratification, monitor disease progression, and assess treatment efficacy, particularly in the presence of comorbidities and the advent of emerging therapies. Conclusions: Multimodal MRI shows considerable promise in translating advanced imaging biomarkers into clinical practice, facilitating the personalized management of DKD. However, future research must focus on establishing standardized imaging acquisition and analytical protocols, conducting prospective cohort studies to validate the association between imaging biomarkers and hard clinical endpoints, integrating artificial intelligence for automated analysis, and developing molecular imaging probes targeted at early disease pathways. Full article

Chronic kidney disease (CKD) represents a considerable health burden for both humans and veterinary patients globally. Renal fibrosis is the final common pathway for the progression of CKD to end-stage renal disease, which can eventually lead to renal failure. Thymoquinone (TQ), the primary bioactive constituent of Nigella sativa, has demonstrated significant antifibrotic potential; however, the specific molecular mechanisms underlying its renoprotective effects remain incompletely elucidated. This study aimed to investigate how TQ alleviates renal fibrosis to support its potential as a therapeutic agent. TQ’s renoprotective effects were evaluated in a murine unilateral ureteral obstruction (UUO) model using histopathology, Western blotting, immunofluorescence, and RT-qPCR. Network pharmacology and untargeted metabolomics were integrated to identify key pathways, which were further assessed through in vivo and in vitro experiments. TQ treatment attenuated UUO-induced renal interstitial injury. TQ treatment downregulated α-smooth muscle actin (α-SMA) and fibronectin, thereby suppressing myofibroblast activation and extracellular matrix (ECM) accumulation. Integrated multi-omics analyses indicated that the antifibrotic activity of TQ is associated with modulation of the PI3K/AKT signaling axis. Subsequent in vivo and in vitro studies suggested that TQ protects against renal injury by inhibiting aberrant PI3K/AKT signaling. This study found that TQ ameliorates renal interstitial fibrosis in UUO mice. The underlying mechanism appears to involve suppression of myofibroblast activation and ECM accumulation via inhibition of PI3K/AKT signaling. These findings highlight the therapeutic potential of TQ for renal fibrosis. Full article

Background/Objectives: Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these mechanisms from the perspective of targeted metabolomics. Methods: The HUA mice constructed by urate oxidase (Uox) gene knockout (KO) and their corresponding wild-type controls were employed for the present study. Serum clinical biochemical parameters were determined, and renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining and Masson’s trichrome staining. A targeted metabolomic strategy based on multiple reaction monitoring (MRM) was utilized to profile the renal metabolic landscape of Uox-KO mice, and potential metabolic biomarkers for CUN were identified via multivariate data analysis. Results: Clinical biochemical analysis revealed a significant elevation in serum uric acid, creatinine, and urea nitrogen levels in Uox-KO mice compared with control mice. Histopathological observations confirmed a typical CUN phenotype in Uox-KO mice, characterized by renal tubular vacuolar degeneration and dilatation, desquamation of tubular epithelial cells into the lumen, neutrophil infiltration, glomerular crowding, and renal interstitial fibrosis. Metabolomic analysis identified a total of 291 differentially regulated metabolites in Uox-KO mice relative to control animals. These perturbed metabolites were involved in multiple key biochemical pathways, including amino acid biosynthesis, ABC transporter signaling pathway, purine metabolism, aminoacyl-tRNA biosynthesis, protein digestion and absorption, glycerophospholipid metabolism, and serotonergic synaptic transmission. Notably, pathological parameters, including biochemical measurements and histological observations, were significantly correlated with key differential metabolites associated with CUN progression. Furthermore, eleven differential metabolites (pyroglutamic acid, fructose, riboflavin, dimethyl-L-arginine, glucaric acid, indoxyl sulfate, palmitoylethanolamide, trimethylamine N-oxide, 3-hydroxyanthranilic acid, spermidine, and hippuric acid) were identified as potential metabolic biomarkers for the diagnosis and prognosis of CUN. Conclusions: These findings illustrate that targeted tissue metabolomic analysis constitutes a powerful tool for deciphering the molecular mechanisms of diseases, thus offering novel insights into the pathogenesis of CUN. Full article

Kidney transplantation remains the optimal treatment for end-stage renal disease, yet long-term allograft survival has plateaued due to persistent rejection. This review provides a comprehensive overview of the inflammatory and immune pathways implicated in kidney allograft rejection, integrating current evidence from basic and translational research. Ischemia–reperfusion injury initiates an inflammatory cascade through the release of damage-associated molecular patterns, activating Toll-like receptors and the complement system, thereby priming the alloimmune response. Innate immune cells, including macrophages, dendritic cells, and natural killer cells, bridge sterile tissue injury to adaptive alloimmunity, while the emerging concept of trained immunity reveals long-lasting epigenetic reprogramming of monocytes with direct implications for graft longevity. The adaptive response encompasses T cell-mediated rejection, driven by Th1, Th17, and CD8⁺ cytotoxic lymphocytes, and antibody-mediated rejection, mediated by donor-specific antibodies through complement activation and antibody-dependent cellular cytotoxicity. Key signalling pathways, including JAK-STAT, NF-κB, NLRP3 inflammasome, and mTOR, amplify allograft inflammation and promote progression toward chronic injury. Macrophage polarisation and macrophage-to-myofibroblast transition have been identified as major drivers of interstitial fibrosis and late graft failure. Recent advances in non-invasive biomarkers, such as donor-derived cell-free DNA and molecular phenotyping, are transforming rejection diagnostics. Emerging therapies, including costimulation blockade, anti-CD38 antibodies, complement inhibitors, and regulatory T cell-based approaches, offer the potential to shift transplant medicine toward precision-guided, tolerance-inducing strategies. This review synthesises these developments and discusses future perspectives for improving long-term allograft outcomes. Full article

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, with renal fibrosis as its core pathological hallmark. A central driver of this fibrosis is epithelial–mesenchymal transition (EMT), during which renal tubular epithelial cells transform into matrix-producing myofibroblasts. Endothelial–mesenchymal transition (EndMT) has also emerged as a critical contributor, and together with EMT, accounts for the progressive accumulation of myofibroblasts and extracellular matrix. A major clinical challenge in halting DKD progression is “metabolic memory”, a phenomenon whereby renal injury persists and EMT/EndMT remain activated even after glycemic control is achieved. The molecular basis underlying this sustained activation remains incompletely understood. Emerging evidence indicates that metabolic memory is largely mediated by epigenetic mechanisms, including histone modifications, DNA methylation, and non-coding RNA dysregulation. These stable epigenetic imprints maintain the persistent activation of key pro-fibrotic signaling pathways, especially TGF-β, thereby continuously driving EMT, EndMT, and excessive extracellular matrix deposition. Although targeting epigenetic regulators has shown promising anti-fibrotic effects, a systematic review that integrates how metabolic memory orchestrates both EMT and EndMT through a multi-layered epigenetic network remains lacking. This review comprehensively summarizes the epigenetic mechanisms by which metabolic memory sustains EMT and EndMT in DKD, highlights key therapeutic targets, and discusses their translational and clinical implications. Full article

Polycystic kidney disease (PKD) is a genetic disorder characterized by renal cyst formation and progressive renal dysfunction, where inflammation, immune responses, and metabolic dysregulation critically drive disease progression, while emerging evidence increasingly links its pathogenesis to mitochondrial dysfunction. Mitochondria, central to cellular energy production, metabolism, and redox homeostasis, exhibit profound abnormalities in PKD, contributing to disease pathogenesis. Current evidence on mitochondrial mechanisms driving PKD progression includes metabolic reprogramming, oxidative stress, disrupted mitochondrial dynamics, and impaired mitophagy. Polycystic kidney disease is caused by mutations in the PKD1 or PKD2 genes, which encode polycystin 1 and polycystin 2. The formation of dysfunctional polycystins (PC1/PC2) is a key event in the pathogenesis of this disease, triggering impaired calcium signaling, increased production of mitochondrial reactive oxygen species (ROS), and reduced oxidative phosphorylation, thereby promoting cyst growth and fibrosis. Key signaling pathways such as mTORC1 hyperactivation, AMPK suppression, and disrupted calcium homeostasis further exacerbate mitochondrial defects. Emerging therapeutic strategies targeting mitochondrial pathways, such as mitochondrial antioxidants, modulators of mitophagy, calcium signaling regulators, and metabolic reprogramming agents, show promise in preclinical models. However, challenges remain in translating these findings to clinical applications, including drug specificity and minimizing off-target effects. This review underscores mitochondria as pivotal players in PKD pathogenesis and highlights their potential as therapeutic targets to mitigate cystogenesis and disease progression. Full article

Cardio-renal metabolic (CRM) syndrome, characterized by insulin resistance and dyslipidemia, disrupts renal insulin signaling, enhances oxidative stress, and activates inflammasome pathways, ultimately promoting renal fibrosis and kidney dysfunction. Aberrant renal gluconeogenesis has emerged as a critical contributor to tubular injury under cardiometabolic stress; however, its mechanistic linkage to inflammatory and fibrotic remodeling remains incompletely defined. In this study, ApoE^−/− mice subjected to streptozotocin administration and a high-fat diet developed pronounced cardiometabolic dysfunction, accompanied by elevated blood urea nitrogen, creatinine, uric acid, and glycated hemoglobin levels, as well as severe renal histopathological alterations. N-Acetylcysteine (NAC) supplementation significantly improved metabolic abnormalities and attenuated tubular dilation, glomerular hypertrophy, and mesangial expansion. Mechanistically, NAC suppressed renal gluconeogenesis by downregulating glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression and mitigated epithelial–mesenchymal transition by restoring E-cadherin and reducing vimentin expression, thereby limiting fibrotic remodeling. Consistent with in vivo findings, NAC reduced reactive oxygen species production, restored PI3K/Akt-dependent insulin signaling, and inhibited inflammasome activation in NRK-52E renal tubular cells exposed to high glucose and oleic acid, resulting in attenuation of inflammatory signaling and gluconeogenic activity. Collectively, these results demonstrate that NAC mitigates cardiometabolic stress-induced renal injury by modulating inflammasome activation and gluconeogenic reprogramming, highlighting its potential as a mechanistic modulator of renal fibrosis under CRM conditions. Full article