Search Results (326)

Objectives: Sjögren’s syndrome (SjS) is a chronic autoimmune disease primarily affecting the salivary and lacrimal glands. Conventional diagnosis depends on invasive procedures, underscoring the need for non-invasive biomarkers. This systematic review summarizes evidence from 2014 to 2024 on the diagnostic and monitoring potential of salivary biomarkers in SjS. Methods: A systematic search of PubMed, Scopus, and Web of Science was performed according to PRISMA guidelines. Eligible human studies investigating salivary biomarkers in SjS were included. Data extraction and quality assessment were conducted independently by two reviewers. The protocol was registered in the OSF Registries. Results: Thirty-one studies were analyzed, identifying diverse metabolomic, proteomic, and molecular biomarkers. Consistent findings included increased levels of lactate, alanine, taurine, NGAL, β₂-microglobulin, annexin A2, and regulatory RNAs (let-7i-5p, miR-17-5p), along with H19 ICR hypomethylation. Several extracellular vesicle (EV)-derived biomarkers demonstrated improved diagnostic stability and specificity. Conclusions: Saliva represents a promising, non-invasive diagnostic medium for Sjögren’s syndrome. Integrating multi-omics approaches-particularly EV-based analyses may enhance early diagnosis and personalized monitoring. Large, multicenter studies using standardized protocols are needed to validate these findings. Full article

Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and life-threatening complication in critically ill children, contributing to high mortality rates (up to 30%) and long-term renal dysfunction in pediatric intensive care units. This review synthesizes recent advances in the signalling pathways underlying SA-AKI, emphasizing pediatric-specific mechanisms, biomarkers, and therapeutic targets. This review covers inflammatory cascades via TLR/NF-κB leading to cytokine storms (IL-6, TNF-α); apoptosis and necrosis involving mitochondrial Bcl-2 dysregulation and OLFM4; and emerging processes like pyroptosis (NF-κB-mediated), metabolic reprogramming (choline deficiency and Nrf2-mitophagy), and novel routes such as cGAS-STING and TGF-β signalling. Biomarkers like urinary OLFM4, DKK3, NGAL, and serum suPAR, alanine, and Penkid enable early diagnosis and risk stratification, with models like PERSEVERE-II enhancing prognostic accuracy. Therapeutic strategies include fluid optimization, renal replacement therapies (CRRT, SLED-f), and pathway-targeted interventions such as choline supplementation, oXiris for cytokine removal, Humanin for immunomodulation, and investigational cGAS-STING inhibitors. Despite progress, challenges persist in translating animal models to pediatric trials and addressing heterogeneity. Integrating multi-omics and precision medicine holds promise for improving outcomes, underscoring the need for multicenter studies in children. Full article

Background/Objectives: Glyphosate-based herbicides (GBHs) are widely used agrochemicals implicated in nephrotoxicity through mechanisms involving oxidative stress, inflammation, and tissue remodeling. Natural peptides such as melittin possess potent anti-inflammatory and antioxidant properties; however, their therapeutic use is limited by instability and toxicity. Nanotechnology-based encapsulation presents a promising approach to overcoming these challenges. Objective: This study aimed to evaluate the protective effects of melittin-loaded chitosan–TPP nanoparticles (MEL-NPs) against glyphosate-induced nephrotoxicity in rats, with emphasis on oxidative, inflammatory, and apoptotic pathways. Methods: Female Wistar rats were divided into four groups: control, glyphosate (5 mg/kg/day, 25 days), glyphosate + free melittin, and glyphosate + MEL-NPs (40 µg/kg, orally, 3 times/week). Renal function biomarkers, oxidative stress parameters (MDA, GSH, SOD, CAT, NO), cytokines (TNF-α, IL-6), and serum protein/iron indices were assessed. Western blotting (Nrf2, NGAL), histopathology (H&E), and immunohistochemistry (Bax) were performed. Nanoparticles were characterized by TEM, FTIR, and UV–Vis spectroscopy. Results: Glyphosate exposure caused renal dysfunction, including elevated plasma urea and creatinine levels, and reduced creatinine clearance, indicating impaired glomerular filtration efficiency, oxidative stress (↑increased MDA, NO; ↓decreased GSH, SOD), and upregulation of pro-inflammatory cytokines. Histology revealed tubular degeneration and inflammatory infiltration, while NGAL and Bax were strongly induced. Nrf2 expression was elevated as a compensatory response. Free melittin partially ameliorated these alterations, whereas MEL-NPs provided superior protection, restoring renal function, normalizing oxidative balance, reducing NGAL and Bax expression, and preserving renal histoarchitecture. Conclusions: Melittin nanoparticles confer robust renoprotection against glyphosate-induced nephrotoxicity in rats by modulating oxidative stress, suppressing inflammation, and regulating Nrf2/Bax signaling. These findings highlight nano-melittin as a promising therapeutic platform for managing herbicide-related renal disorders. Full article

Secondary peritonitis is a life-threatening intra-abdominal condition arising from gastrointestinal perforation, chemical injury, or catheter-related infections, characterized by marked heterogeneity in presentation and progression. Major subtypes include stercoraceous peritonitis with fecal contamination, fibrinous peritonitis triggered by bile or gastric contents, peritoneal dialysis-associated infections, and pancreatitis-associated chemical peritonitis. Regardless of etiology, these conditions share profound local and systemic inflammatory responses, contributing to high morbidity and mortality. Biomarkers such as procalcitonin (PCT), interleukin-6 (IL-6), high mobility group box 1 (HMGB1), C-reactive protein (CRP), lipopolysaccharide (LPS), neutrophil-to-lymphocyte ratio (NLR), and neutrophil gelatinase-associated lipocalin (NGAL) have emerged as tools for early diagnosis, subtype stratification, and monitoring of therapeutic response. Their prognostic value is particularly relevant in peritoneal dialysis and postoperative intensive care. Advances in multi-omics, patient-derived organoids, peritoneum-on-chip models, and microbiota profiling are reshaping understanding of peritoneal pathophysiology, revealing cellular heterogeneity, immune-microenvironment interactions, and mechanisms of fibrotic remodeling. Key translational challenges include assessing whether omics-derived signatures can predict the need for early re-laparotomy or the risk of abdominal compartment syndrome. Integration of high-dimensional biomarker profiling with mechanistic and functional studies promises a new era of precision medicine in secondary peritonitis, enabling risk-adapted interventions, complication prevention, and tailored strategies to improve outcomes. Full article

Background: Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection leading to organ dysfunction. Distinguishing sepsis from localized infection is crucial, as it guides clinical decision-making and biomarker interpretation. Biomarkers may support diagnosis, prognosis, and therapeutic choices, but their integration into practice remains debated. Methods: This narrative review was conducted in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. A comprehensive literature search was performed in PubMed, Embase, and Cochrane CENTRAL (January 2000–September 2025). Studies evaluating sepsis-related biomarkers for diagnosis, prognostication, shock assessment, antimicrobial stewardship, and post-acute follow-up were considered. Findings: Established biomarkers such as procalcitonin (PCT), C-reactive protein (CRP), and lactate remain widely used for diagnosis, monitoring of inflammatory response, and assessment of severity. Emerging candidates include pancreatic stone protein (PSP), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte HLA-DR (mHLA-DR), which may provide insights into infection dynamics, renal injury, and immune suppression, respectively. However, limitations in standardization and heterogeneous evidence hinder routine implementation. Interleukin-6 (IL-6), despite extensive study, shows limited specificity and inconsistent clinical applicability. Renin has been proposed as a marker of shock severity rather than infection. Comparative evidence highlights the need for stage-specific biomarker use across prehospital, emergency, ICU, and recovery phases. Conclusions: No single biomarker is universally applicable in sepsis. Their utility depends on timing, clinical setting, and patient phenotype. Combining classical and emerging biomarkers with point-of-care technologies and dynamic monitoring may enhance personalized management. Limitations include heterogeneity of evidence and lack of standardized thresholds. Future research should validate biomarker panels, integrate them into stewardship strategies, and explore their cost-effectiveness in clinical practice. Full article

Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck^® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Chronic kidney disease (CKD) poses a global burden affecting over 10% of the adult population worldwide. Acute kidney injury (AKI) is an important cause of CKD, especially following severe and repeated episodes. However, the processes underpinning progressive and chronic renal deterioration after AKI are only incompletely understood. Thus, models reproducing this scenario are needed to study the pathophysiological mechanisms involved and identify biomarkers and molecular targets for diagnostic and therapeutic purposes. In this study, we developed a rat model of 3 serial AKIs leading to CKD, in which renal function, kidney structure and fibrosis, and urinary injury biomarkers were studied over a period of 9 months, alongside a traditional model of CKD caused by renal mass reduction. Our results show that consecutive AKIs eventually develop key features of CKD including progressive fibrosis and albuminuria. Renal injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and retinol binding protein 4 (RBP4) show distinct evolution patterns suggestive of specific but undetermined damages with different time courses. The chronic evolution of renal tissue degeneration and dysfunction following serial AKIs closely resembles those observed after extensive renal mass reduction, which indicates chronic degeneration. Finally, a clear dissociation in the evolution of interstitial fibrosis (progressively increasing) and of glomerular filtration (mainly stable) was observed in both models. This questions the consuetudinary paradigm ascribing an etiological role to fibrosis in progressive renal dysfunction. Full article

Background and Objectives: Lupus nephritis (LN) is a major cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE). Biomarkers derived from blood, urine, and multi-omics techniques are essential for enabling access to less invasive methods for LN evaluation and personalized precision medicine. Materials and Methods: The purpose of this work was to review the studies that addressed the potential role of urinary and serological biomarkers for the diagnosis, disease activity, response to treatment, and renal outcome of adult patients with LN, published over the past decade, and summarize their results with a particular emphasis being directed towards the available traditional tools. Results: Traditional biomarkers used for the diagnosis and surveillance of LN are proteinuria, urinary sediment, estimated glomerular filtration rate (eGFR), anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-C1q, and serum complement levels. Anti-dsDNA, serum C3, and proteinuria are the conventional biomarkers with the strongest clinical evidence, with overall moderate ability in predicting LN from non-renal SLE, disease activity, renal flares, response to therapy, and prognosis. The last decade has brought significant progress in our understanding regarding the pathogenesis of LN and, consequently, several molecules, either alone or in combination panels, have emerged as potential novel biomarkers, some of them outperforming conventional biomarkers. Promising results have been suggested for urinary activated leukocyte cell adhesion molecule (ALCAM), soluble cluster of differentiation 163 (CD163), C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein 1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and vascular cell adhesion molecule 1 (VCAM-1). Conclusions: Despite the intensive research of the last decade, no novel biomarker has entered clinical practice, and we continue to rely on traditional biomarkers to assess non-invasively LN and guide its treatment. Novel biomarkers should be validated in multiple longitudinal independent cohorts, compared with conventional biomarkers, and integrated with renal histology information in order to optimize the management of LN patients. Full article

Background: A deregulated aldosterone (Aldo)–mineralocorticoid receptor (MR) pathway is linked to cardiovascular disease (CVD), including hypertension and heart failure. Despite the association of elevated plasma Aldo levels with cardiac stress, inflammation, myocardial fibrosis, and cardiac remodeling, the underlying mechanisms remain elusive. Methods: To study the impact of Aldo–MR pathway overactivation on cardiac health, a novel mouse model with AAV9-mediated MR overexpression and Aldo administration via subcutaneous osmotic pumps was generated. Echocardiographic analyses, transcriptome sequencing, and loss-of-function experiments of an identified lead candidate gene were performed. Additionally, cardiac tissue samples from human patients with end-stage heart failure were analyzed in the study. Results: Mice with an overactivated Aldo–MR pathway exhibited increased neutrophil gelatinase-associated lipocalin (NGAL) expression, cardiac dysfunction, hypertrophy, and fibrosis. Transcriptomics identified prostaglandin D₂ synthase (Ptgds) as a novel downstream effector of the cardiac Aldo–MR pathway. SiRNA-mediated inhibition of Ptgds in primary cardiomyocytes reduced NGAL levels and the hypertrophic impact of Aldo, suggesting a role in mediating Aldo-induced cardiac pathologies. Elevated expression of PTGDS was observed in hiPSC-CMs treated with the pro-hypertrophic cytokine leukemia inhibitory factor (LIF) and in end-stage heart failure patients, ascertaining its importance in cardiac disease settings. Conclusions: PTGDS is a newly identified mediator of Aldo–MR-induced cardiac remodeling and may represent a potential therapeutic target for CVD. Full article

Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article

Acute kidney injury is a common complication in the perioperative setting, especially among patients undergoing high-risk surgeries such as cardiac, abdominal, or orthopedic procedures. Characterized by a sudden decline in renal function, perioperative acute kidney injury is typically diagnosed based on rising serum creatinine or reduced urine output. Its incidence varies depending on the surgical type and patient risk factors, but even mild cases are linked to significant consequences, including prolonged hospital stays, enhanced healthcare costs, and higher mortality rates. Despite advances in surgical and anesthetic care, acute kidney injury remains a major cause of morbidity. The development of acute kidney injury in the perioperative period often results from a complex interplay of hypoperfusion, ischemia–reperfusion injury, inflammation, and exposure to nephrotoxic agents. While some predictive models and biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), have shown promise in identifying patients at risk, widespread adoption remains inconsistent, and standardized prevention protocols are lacking. This narrative review synthesizes current evidence on the pathophysiology, risk factors, and prevention strategies for perioperative acute kidney injury. It explores emerging tools for risk stratification and early diagnosis, including novel biomarkers and learning-based models. Additionally, it highlights pharmacologic and non-pharmacologic measures to reduce acute kidney injury incidence, such as balanced fluid management, renal-protective anesthetic strategies, and bundle-based care approaches. Emphasizing a multidisciplinary and personalized model of care, this review highlights the need for coordinated efforts between anesthesiologists, surgeons, and nephrologists to identify modifiable risks and improve outcomes. Reducing the incidence of perioperative acute kidney injury has the potential to enhance recovery, preserve long-term kidney function, and ultimately improve surgical safety. Full article

Background: Peritonitis in peritoneal dialysis and cirrhosis remains common and leads to morbidity. Neutrophil gelatinase-associated lipocalin (NGAL) has been evaluated as a rapid adjunctive biomarker. Methods: Following PRISMA-DTA and PROSPERO registration (CRD420251105563), we searched MEDLINE, Embase, Cochrane Library, LILACS, Scopus, and Web of Science from inception to 31 December 2024, and ran an update on 30 June 2025 (no additional eligible studies). Diagnostic accuracy studies measuring NGAL in peritoneal/ascitic fluid against guideline reference standards were included. When 2 × 2 data were not reported, we reconstructed cell counts from published metrics using a prespecified, tolerance-bounded algorithm (two studies). Accuracy was synthesized with a bivariate random effects (Reitsma) model; 95% prediction intervals (PIs) were used to express heterogeneity; small-study effects were assessed by Deeks’ test. Results: Thirteen studies were included qualitatively and ten were entered into a meta-analysis (573 cases; 833 controls). The pooled sensitivity was 0.95 (95% CI, 0.90–0.97) and specificity was 0.86 (0.70–0.94); likelihood ratios were LR+ ≈7.0 and LR− 0.06. Between-study variability was concentrated on specificity: the PI for a new setting was 0.75–0.98 for sensitivity and 0.23–0.99 for specificity. Deeks’ test showed evidence of small-study effects in the primary analysis; assay/platform and thresholding contributed materially to heterogeneity. Conclusions: NGAL in peritoneal/ascitic fluid demonstrates high pooled sensitivity but variable specificity across settings. Given the wide prediction intervals and the signal for small-study effects, NGAL should be interpreted as an adjunct to guideline-based criteria—not as a stand-alone rule-out test. Standardization of pre-analytics and assay-specific, locally verified thresholds, together with prospective multicenter validations and impact/economic evaluations, are needed to define its clinical role. Full article

Chronic kidney disease (CKD) is a global public health issue linked to toxic elements like cadmium (Cd) and mercury (Hg), which harm the kidneys even at low exposure levels. Copper (Cu) and zinc (Zn) imbalances could exacerbate inflammation, oxidative stress, and kidney damage because the Cu/Zn ratio could be a critical marker of renal dysfunction. The study evaluated 914 adolescents aged 11–18 through urine samples to assess the presence of kidney damage biomarkers (OPN, KIM-1, CLU, NGAL, and Cys-C) by using Luminex Magpix and trace metals (Cd, Hg, Cu, Zn) by using ICP-mass. Overweight (18.71%) and obesity (12.58%) rates were noted. Cd and Cu showed positive correlations with kidney damage biomarkers, while Zn exhibited protective effects. Regression models indicated that Cd exposure increased kidney damage markers, emphasizing the importance of Cu/Zn ratio. Environmental exposure to Cd affects kidney health even at low levels, as the Cu/Zn ratio correlates with kidney damage markers in low-Cd exposure, suggesting that the Cu/Zn ratio could participate in the nephrotoxicity process, highlighting trace element imbalance as a potential predictor of kidney function decline. Full article

Polytrauma is a critical global health concern characterized by immune dysregulation and a high risk of multiple organ dysfunction syndrome (MODS). Early molecular mechanisms linking trauma severity to organ injury are poorly understood. We used two rat blast-polytrauma models: a tourniquet-induced ischemia/reperfusion injury (tIRI) model and a non-ischemia/reperfusion injury (non-IRI) model. Naïve animals served as controls. RT-qPCR of 120 inflammatory genes in the lung, kidney, and liver, combined with STRING protein–protein interaction analysis, revealed distinct yet overlapping inflammatory gene signatures across all the organs. A core set of genes (Il6, Lbp, Nos2, and Lcn2) was consistently upregulated, indicating shared inflammatory pathways. Transcriptomic responses were most pronounced in the tIRI group, with greater magnitude and altered temporal dynamics, uniquely amplifying pro-inflammatory cytokines, immune cell activators, chemokines, and tissue damage markers. Lipocalin-2 (Lcn2/NGAL) emerged as a shared hub gene across all the organs within 24 h post-injury. Its expression significantly correlated with MODS activity and adverse outcomes, independent of the injury model. At 168 h, Lcn2 expression correlated with increased liver damage and NGAL levels correlated with tissue trauma severity. These findings elucidate distinct pro-inflammatory mediators and networks underlying secondary organ dysfunction, highlighting NGAL as a potential universal biomarker of trauma-induced inflammation and MODS activity, suggesting it as a therapeutic target. Full article