Search Results (790)

Background: Acute kidney injury (AKI) is associated with poor outcomes in patients with cirrhosis. However, most studies evaluate AKI as a single clinical entity, whereas predictors of mortality and renal recovery, specifically in non-hepatorenal syndrome AKI (non-HRS-AKI), remain poorly defined. Methods: We performed a retrospective cohort study including consecutive patients with liver cirrhosis admitted with non-HRS-AKI to a multidisciplinary emergency hospital between 1 January 2024 and 31 December 2025. Only variables available at hospital admission were included in the multivariable analyses. Independent predictors of in-hospital mortality and factors associated with incomplete renal recovery in survivors at hospital discharge were identified using multivariable logistic regression. Results: A total of 139 patients were included. Overall, 57 patients (41.0%) died during hospitalization. Among the 82 survivors, complete renal recovery occurred in 35 cases (42.7%), whereas 47 patients (57.3%) had incomplete renal recovery at discharge. Independent predictors of in-hospital mortality were a higher MELD-Na score (adjusted OR 1.16 per 1-point increase, 95% CI 1.07–1.26; p < 0.001), an advanced AKI stage (KDIGO stage 3 vs. stage 1, adjusted OR 6.71, 95% CI 1.73–26.04; p = 0.006), the absence of pre-existing chronic kidney disease (adjusted OR 0.233, 95% CI 0.085–0.644; p = 0.005), and higher admission C-reactive protein (adjusted OR 1.12 per 10 mg/L increase, 95% CI 1.01–1.23; p = 0.029). Factors independently associated with incomplete renal recovery among hospital survivors at hospital discharge were pre-existing heart failure (adjusted OR 3.07, 95% CI 1.10–8.62; p = 0.033) and higher admission C-reactive protein (adjusted OR 1.17 per 10 mg/L increase, 95% CI 1.00–1.34; p = 0.047). Conclusions: In patients with cirrhosis-associated non-HRS-AKI, in-hospital mortality was primarily associated with the severity of liver disease and AKI, whereas incomplete renal recovery at hospital discharge was independently associated with pre-existing heart failure. Admission C-reactive protein was independently associated with both outcomes, supporting the role of systemic inflammation in determining short-term prognosis and suggesting that C-reactive protein may serve as a simple, readily available biomarker for early risk stratification. Full article

Cardiovascular–kidney–metabolic (CKM) syndrome encompasses the convergent pathophysiology of obesity, insulin resistance, type 2 diabetes, chronic kidney disease, and cardiovascular disease, conditions whose interactions account for a substantial proportion of cardiovascular morbidity and mortality despite contemporary guideline-directed therapy. Nitric oxide (NO) pathway dysfunction constitutes a unifying mechanism across this continuum, linking endothelial dysfunction, impaired insulin signaling, and multiorgan injury through endothelial NO synthase (eNOS) uncoupling, increased arginase activity, asymmetric dimethylarginine (ADMA) accumulation, and paradoxical inducible NO synthase (iNOS)-driven nitrosative stress. Established cardiometabolic therapies—sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), renin–angiotensin–aldosterone system (RAAS) inhibitors, statins, and metformin—improve NO signaling indirectly through reductions in oxidative stress and inflammation yet fail to fully restore NO bioavailability and leave substantial residual cardiovascular and renal risk unaddressed. Direct NO-restoring strategies, including soluble guanylate cyclase (sGC) modulators, arginase inhibition, ADMA-lowering approaches, and microbiome-targeted interventions, demonstrate mechanistic promise in preclinical and early translational studies but currently lack outcome-level evidence. Biomarkers of NO pathway dysfunction—ADMA, flow-mediated dilation (FMD), the tetrahydrobiopterin–dihydrobiopterin (BH4/BH2) ratio, cyclic guanosine monophosphate (cGMP), and endothelial microparticles (EMPs)—offer a foundation for patient phenotyping but remain insufficiently standardized for clinical use. A NO-centered framework provides a biologically coherent model for understanding residual cardiometabolic risk; its translation into personalized therapy will require validated biomarker panels and biomarker-guided outcome trials. Full article

Serum creatinine (sCr), blood urea nitrogen (BUN) and symmetric dimethylarginine (SDMA) reflect glomerular filtration only and are subject to non-renal confounders including lean body mass, limiting early detection of renal dysfunction in geriatric dogs. We evaluated serum cystatin C (sCysC) and the urinary N-acetyl-β-D-glucosaminidase-to-creatinine ratio (NAG index) as early renal markers in healthy geriatric dogs. Sixty-one neutered geriatric dogs, free of clinical disease and of extrarenal laboratory abnormalities, were stratified into three groups: controls (n = 36), subclinical (normal sCr, ≥1 elevated biomarker; n = 17) and azotaemic chronic kidney disease (CKD; sCr > 1.5 mg/dL; n = 8). sCysC was measured by a canine-specific ELISA and the NAG index by colorimetric assay. Of the 61 dogs, 17 (27.9%) had at least one elevated biomarker with normal sCr, and all 17 also had normal BUN, indicating pre-azotaemic changes identified predominantly by sCysC. The NAG index was elevated in 6/17 (35.3%) subclinical dogs and SDMA in none (0/17). Because sCysC status partly informed group allocation and no independent measure of glomerular filtration rate was obtained, these findings characterise an altered renal biochemical phenotype rather than establish diagnostic accuracy, and require prospective validation. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease frequently accompanied by depression, with persistent inflammation, oxidative stress, and neuroimmune dysfunction contributing to disease progression. This study evaluated the therapeutic efficacy of a Gum Arabic-stabilized bioactive oil blend nanoemulsion and investigated its underlying mechanisms using molecular docking and network pharmacology. Methods: A lyophilized nanoemulsion prepared from grape seed oil, wheat germ oil, and avocado peel oil was characterized for physicochemical properties and phytochemical composition. Female rats with Freund’s complete adjuvant-induced rheumatoid arthritis received the nanoemulsion at two doses. Paw inflammation, behavioral performance, inflammatory cytokines, oxidative stress biomarkers, acetylcholinesterase concentration, lipid profile, and liver and kidney function were evaluated. Molecular docking and network pharmacology analyses were performed to identify potential molecular targets and signaling pathways. Results: The nanoemulsion exhibited favorable physicochemical characteristics and was rich in phenolic compounds, flavonoids, phytosterols, tocopherols, and unsaturated fatty acids. Treatment significantly reduced paw inflammation, TNF-α, IL-6, malondialdehyde, and acetylcholinesterase while enhancing catalase activity, improving metabolic parameters, and alleviating depression-like behavior. Molecular docking demonstrated favorable binding of the major phytochemicals to TNF-α, IL-6, and acetylcholinesterase. Network pharmacology identified key therapeutic targets, including TNF, AKT1, PTGS2, IL6, STAT3, ESR1, and NR3C1, and revealed enrichment of inflammatory, oxidative stress, and neuroimmune signaling pathways. Conclusions: The Gum Arabic-stabilized bioactive oil blend nanoemulsion ameliorated rheumatoid arthritis-associated depression-like behavior through a multi-component–multi-target–multi-pathway mechanism involving coordinated regulation of inflammatory, oxidative stress, cholinergic, and neuroimmune pathways. These findings support its potential as a complementary nutraceutical strategy for rheumatoid arthritis and its associated neurobehavioral complications. Full article

The heart–kidney axis has emerged as a central framework for understanding the bidirectional interactions that drive cardiorenal syndrome and broader cardiovascular–kidney–metabolic (CKM) disease. However, existing interpretations have often emphasized hemodynamic and neurohormonal mechanisms without fully integrating the growing evidence for endocrine, inflammatory, and metabolic mediators that coordinate injury across organs. This Review was therefore undertaken to provide an updated and clinically relevant synthesis of the physiological basis of heart–kidney communication, the mechanisms underlying its disruption, and the therapeutic implications of these insights. To achieve this aim, we performed a systematic narrative review of the literature using PubMed, Embase, Web of Science, and Scopus for studies, supplemented by manual screening of reference lists. Priority was given to original studies, large cohort analyses, randomized controlled trials, meta-analyses, and authoritative reviews. We integrated evidence spanning physiological regulation, maladaptive signaling pathways, emerging mediators, experimental models, and evolving treatment strategies. The reviewed evidence indicates that heart–kidney crosstalk is driven not only by altered perfusion and venous congestion, but also by sustained activation of the renin–angiotensin–aldosterone system (RAAS) and sympathetic nervous system (SNS), inflammation, oxidative stress, mitochondrial dysfunction, anemia, uremic toxins, and disordered mineral metabolism. Among novel mediators, fibroblast growth factor 23 (FGF23) emerges as a major bone-derived, chronic kidney disease (CKD)-associated endocrine mediator linking renal injury to cardiac hypertrophy, fibrosis, calcium mishandling, and diastolic dysfunction, whereas Klotho appears to exert counter-regulatory protective effects. Heart-derived natriuretic peptides, including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), remain important modulators of renal blood flow, natriuresis, and volume homeostasis. We further highlight the translational relevance of newer biomarkers and therapies, including sodium–glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), and mineralocorticoid receptor antagonists (MRAs), which may help address cardiac and renal dysfunction in parallel. Overall, this Review supports a revised conceptual model in which the heart–kidney axis is governed by multidirectional hemodynamic, neurohormonal, immune, and endocrine signaling networks. A more integrated understanding of these mechanisms may improve biomarker discovery, refine risk stratification, and promote therapies that target both organs simultaneously. Full article

Chronic kidney disease (CKD) requires assessment of both glomerular filtration and kidney damage, particularly albuminuria, for diagnosis, risk stratification, and longitudinal care. Point-of-care testing (POCT) can shorten turnaround time and improve access when conventional laboratory testing is unavailable or would delay a clinical pathway. This narrative review summarizes established and emerging POCT approaches for kidney assessment in CKD, with emphasis on creatinine/eGFR and urine albumin-to-creatinine ratio (UACR), and distinguishes analytical validity from workflow utility and patient-level clinical utility. Evidence is strongest for rapid creatinine measurement in selected workflows, especially pre-imaging assessment and decentralized screening, while quantitative/semiquantitative UACR POCT can support CKD detection when abnormal results are appropriately confirmed. Cystatin C microfluidic systems remain investigational, and kidney injury/stress or molecular biomarkers such as NGAL, KIM-1, L-FABP, [TIMP-2]·[IGFBP7], extracellular vesicles, and microRNAs should be regarded primarily as a research horizon rather than direct measures of GFR. Important implementation requirements include assay-specific validation, calibration traceability, quality assurance, recognition of biological and analytical interference, and confirmation of results near major clinical decision thresholds. Evidence that POCT improves long-term CKD outcomes, safety, adherence, or cost-effectiveness remains limited. Future studies should prioritize prospective clinical utility, implementation, cost-effectiveness, home-use validation, and patient-centered outcomes. Full article

Background/Objectives: Distinguishing glomerulonephritis (GN) from diabetic kidney disease (DKD) and nephrosclerosis (NS) is clinically important. Urinary uromodulin (uUMOD), a biomarker of renal tubular integrity, may help discriminate among these chronic kidney disease (CKD) etiologies. We evaluated the diagnostic utility of uUMOD for differentiating GN from DKD and NS. Methods: This retrospective single-center study included 90 patients with biopsy-proven GN (n = 30), DKD (n = 25), or NS (n = 35). First-morning spot urine samples obtained before biopsy were analyzed for uUMOD concentration and normalized to urinary creatinine levels (uUMOD/Cr). Results: The uUMOD/Cr ratio was significantly higher in GN (21.2 mg/gCr [10.3–31.3]) than in DKD (5.5 [3.6–12.3], p < 0.001) or NS (10.7 [6.4–19.9], p = 0.021). In multivariate analyses adjusted for age, sex, estimated glomerular filtration rate, interstitial fibrosis, and urinary protein, the uUMOD/Cr ratio was independently associated with GN (p = 0.003) and this correlation remained statistically significant after additional adjustment for diabetes mellitus. Receiver operating characteristic curve analysis showed an area under the curve value of 0.833 for GN versus DKD, 0.714 for GN versus NS, and 0.764 for GN versus DKD and NS combined. A cutoff value of 16.5 mg/gCr yielded 72.8% sensitivity and 70.0% specificity for identifying GN. Conclusions: uUMOD secretion is preserved in GN compared to DKD or NS and shows moderate diagnostic utility for differentiating between these biopsy-proven CKD etiologies. uUMOD may serve as a simple, noninvasive biomarker when biopsy is difficult or clinical findings are inconclusive. Full article

Chronic kidney disease (CKD) represents a rising global health crisis traditionally monitored through routine biochemical markers that may not fully reflect underlying structural alterations. While renal biopsy remains the invasive reference standard for histopathological assessment, ultrasound elastography, particularly shear wave elastography (SWE), has emerged as a promising non-invasive imaging technique for assessing the mechanical properties of the renal parenchyma. This narrative review examines the role of renal elastography in adult nephrology, linking the pathophysiology of renal fibrosis with advances in clinical imaging. We discuss the biological mechanisms underlying changes in renal tissue biomechanics and review the available evidence regarding the association between elastography-derived stiffness measurements and histopathological fibrosis in native kidneys and renal allografts. Although several studies have demonstrated promising diagnostic potential, the clinical interpretation of renal stiffness remains challenging due to tissue anisotropy, renal perfusion and congestion, inflammation, obstruction, hydration status, body habitus, and acquisition-related factors. Current evidence supports renal elastography primarily as a potential adj method to conventional clinical, biochemical, and imaging assessment rather than as a replacement for kidney biopsy. Future integration of elastography with artificial intelligence, multiparametric ultrasound, and molecular biomarkers may further improve non-invasive renal phenotyping, although multicentre and longitudinal validation are required before widespread clinical use. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) requires practical and inexpensive tools for risk stratification. We investigated whether the red cell distribution width (RDW), a routinely available hematologic parameter, predicts adverse clinical outcomes, using data from 352,623 UK Biobank participants, including 165,700 individuals with MASLD. RDW was analyzed as both a continuous and categorical variable using Cox proportional hazards models, restricted cubic splines, inverse probability treatment weighting, landmark, competing risk, and mediation analyses. Over a median follow-up of 13.6 years, each 1% increase in RDW was independently associated with higher risks of all-cause mortality (hazard ratio [HR] 1.14), cardiovascular disease (HR 1.07), cerebrovascular disease (HR 1.07), and chronic kidney disease (HR 1.09) (all p < 0.001). These associations remained consistent across multiple sensitivity analyses, and conventional biomarkers explained a modest proportion of the observed associations. Oxidative stress, together with other systemic processes affecting erythrocyte homeostasis, represents one potential mechanism underlying these associations. Higher RDW was independently associated with adverse clinical outcomes after adjustment for routine liver and metabolic biomarkers, supporting its potential value as a readily available prognostic marker in MASLD. Full article

Chronic kidney disease (CKD) is sustained by a network of sterile inflammation, oxidative and metabolic stress, uremic toxin retention, gut barrier dysfunction, and maladaptive immune activation. These processes contribute to kidney fibrosis, cardiovascular injury, wasting, and excess mortality, but inflammatory biomarkers do not by themselves establish therapeutic causality. This narrative review integrates mechanistic and therapeutic evidence using an explicit three-layer translational hierarchy. Renin–angiotensin system inhibitors, sodium–glucose cotransporter-2 inhibitors, finerenone, and glucagon-like peptide-1 receptor agonists improve cardiorenal outcomes and have plausible anti-inflammatory actions, although inflammatory mediation remains unproven. Interleukin-1 blockade provides cardiovascular proof of principle and small dialysis feasibility data. Interleukin-6 ligand inhibition produces marked human target engagement; however, headline results from the completed phase 3 ZEUS trial showed no reduction in three-point major adverse cardiovascular events with ziltivekimab despite biomarker suppression, while serious infections were more frequent. POSIBIL6ESKD continues to test clazakizumab in inflamed dialysis patients. Direct NLRP3 inhibition has entered early human CKD development, whereas senescence-directed and microbiota-based approaches remain less mature. Future progress requires inflammatory endotyping, repeated biomarker assessment, mechanistically aligned outcomes, and rigorous infection surveillance. ZEUS underscores that pathway suppression must deliver clinical benefit beyond contemporary standard therapy. Full article

Cardiac surgery-associated acute kidney injury (CS-AKI) increases short- and long-term mortality, progression to chronic kidney disease (CKD), and healthcare costs. Its pathogenesis is multifactorial—combining renal hypoperfusion, impaired oxygen delivery, hemodilution, inflammation, ischemia–reperfusion injury, and nephrotoxin exposure—so no single intervention confers universal protection. This narrative review appraises fourteen perioperative prevention strategies, grading each by study design, reproducibility, and concordance with contemporary guidelines. The strongest actionable evidence supports the preservation of renal oxygen delivery during cardiopulmonary bypass through goal-directed perfusion, perioperative amino acid infusion, and biomarker-guided Kidney Disease: Improving Global Outcomes (KDIGO) care bundles. Remote ischemic preconditioning, pulsatile flow, minimally invasive extracorporeal circulation, dexmedetomidine, N-acetylcysteine, levosimendan, hemoadsorption with the oXiris membrane, and natriuretic peptides show variable or subgroup-dependent signals limited by heterogeneous trial design and acute kidney injury (AKI) definitions. Prevention of CS-AKI is, therefore, best conceived as a multimodal, patient-centered process integrating preoperative risk stratification, intraoperative oxygen delivery optimization, patient blood management (PBM), and postoperative nephrotoxin avoidance and surveillance. Full article

Trimethylamine N-oxide (TMAO) and homocysteine are key biomarkers linked to cardiovascular and chronic kidney disease (CKD). Although they originate from distinct metabolic pathways, their circulating levels are jointly shaped by renal clearance, systemic metabolic status, and nutrient availability, complicating their biological interpretation. TMAO derives from gut microbiota–dependent metabolism of dietary precursors followed by hepatic oxidation of trimethylamine, whereas homocysteine is a central intermediate of one-carbon metabolism governed by remethylation and transsulfuration. Choline and betaine provide a nutritional interface between these pathways because choline can contribute to microbial TMA production and betaine acts as a methyl donor for homocysteine remethylation via betaine–homocysteine methyltransferase (BHMT). However, this interface does not establish direct metabolic interdependence between circulating TMAO and homocysteine. Declining renal function promotes the accumulation of both TMAO and homocysteine, although their renal handling and the mechanisms underlying their increase in CKD are not identical. Experimental and clinical evidence also links both metabolites to partially overlapping downstream processes, including oxidative stress, inflammation, endothelial dysfunction, and fibrotic remodeling. These shared pathophysiological responses should be distinguished from convergence of their biosynthetic pathways. This narrative review examines how renal function, metabolic regulation, and nutritional factors influence TMAO and homocysteine biology, emphasizing renal handling, analytical variability, shared downstream mechanisms, and the limitations of isolated measurements. A shift toward context-aware, multiparametric assessment may enhance their interpretation in cardiorenal research, although neither biomarker currently replaces established measures of kidney function. Full article

Background and Objectives: Topical diclofenac is recommended over oral non-steroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis, particularly in older adults and those with comorbidities, on the assumption that low systemic absorption limits renal effects. Whether this presumed safety extends to patients already at increased risk of kidney injury has not been systematically evaluated. This review assessed the evidence on renal outcomes of topical diclofenac in adults. Materials and Methods: We conducted a systematic review (PROSPERO CRD420261393454) of studies reporting renal outcomes after topical diclofenac exposure. PubMed, Embase, Web of Science, and Scopus were searched from inception to 19 April 2026. Studies were stratified a priori into increased-renal-risk and general populations and synthesised separately, without pooling. Risk of bias was assessed with RoB 2, ROBINS-I, and JBI tools, certainty with GRADE, and synthesis followed the SWiM framework. Results: Eighteen studies, contributing data from more than 500,000 participants, were included; 14 underwent primary risk-of-bias appraisal (three at low, three at serious or high risk). In general populations, topical diclofenac produced little to no change in serum creatinine or creatinine clearance and smaller renal effects than oral diclofenac, providing high-certainty evidence of a favourable profile. In increased-renal-risk populations, one adjusted cohort reported higher acute kidney injury (AKI) risk among topical NSAID users, although exposure was predominantly to non-diclofenac agents; within the same cohort, topical NSAIDs carried lower risk than systemic NSAIDs. No study evaluated early renal injury biomarkers; certainty was moderate owing to indirectness. Conclusions: Relative to oral diclofenac, topical diclofenac shows a favourable renal safety profile, with high-certainty evidence in general populations. In adults at increased renal risk, moderate-certainty evidence derived from predominantly non-diclofenac exposure over short observation windows cannot exclude a modest excess of any-stage AKI; renal risk therefore appears reduced rather than absent. Diclofenac-specific studies in chronic kidney disease using sensitive biomarkers and longer follow-up are needed. Full article

Exosomes have emerged as key mediators of intercellular and inter-organ communication. Although substantial advances have expanded the understanding of the biology of extracellular vesicles, exosome biogenesis and their role in the disease progression of systemic diseases have not yet been fully elucidated. In this review, we present a comprehensive overview of the molecular pathways responsible for exosome biogenesis, emphasizing how the selective incorporation of proteins, lipids, metabolites, messenger RNAs, and microRNAs (miRs) determines the composition and biological activity of exosomes. We also discuss how exosome-mediated inter-organ communication functions as an integrated biological network that connects the kidney, the cardiovascular system, the brain, the liver, the immune system, and tumors, thereby coordinating the pathological responses underlying the progression of chronic diseases. Additionally, we demonstrate the recent advances in the potential of exosomes as minimally invasive biomarkers and clinical translational implantation. Finally, we discussed the methodological and biological challenges that limit the clinical application of exosomes. Overall, this review presents an integrated framework for understanding exosome biology and supports the concept that exosomes function as dynamic platforms for systemic signaling that link molecular mechanisms to disease pathogenesis and translational medicine. Full article

Background/Objectives: Cardiorenal syndrome (CRS) is associated with substantially higher morbidity and mortality than either isolated cardiac or renal dysfunction. The application of classical and novel biomarkers has been tested in prompt diagnosis and monitoring of patients with CRS. Methods: This is a comprehensive literature review following a structured approach. We searched MEDLINE and Embase databases from January 2000 to December 2025. Results: The pathophysiology of CRS is complex, and the present review attempts to shed light on the clinical interpretation of the most widely used biomarkers as indices of diagnosis and prognosis. Among them, troponin is elevated in CRS and its absolute levels retain prognostic value, while changes in its levels over time may assist in the diagnosis of acute coronary syndrome. Natriuretic peptides are highly influenced by coexistence of chronic kidney disease (CKD) and in this context have considerable diagnostic and prognostic value. The combination of cystatin C, a biomarker of renal dysfunction, with cardiac biomarkers may create a powerful risk algorithm. Most recently, gene profiling and proteomics have the potential to stratify patients with CRS; however, more data from large cohorts are required for their validation. The therapeutic modulation of biomarkers in CRS patients may help elucidate the underlying pathophysiologic mechanisms. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as first-line therapy for patients with CRS, despite the fact their mechanisms are mostly unknown. Significant changes in the aforementioned biomarkers and the inflammatory factors may explain their emerging beneficial effects on both heart failure and CKD. Conclusions: The use of biomarkers has increased rapidly in recent years for diagnosis, surveillance and prognostic stratification in CRS. Full article