Search Results (3,515)

Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction. Advanced glycation end-products [AGEs] and their receptor [RAGE] mediate glycoxidative stress, whereas mitochondrial-derived peptides [MDPs], including humanin [HN], MOTS-c, and humanin-like 1 [HN-L1], regulate mitochondrial stress responses. We investigated links between AGE–RAGE activation and mitochondrial signaling in CKD. Methods. Serum AGEs, soluble RAGE isoforms, and MDPs were measured by ELISA in 160 adults with kidney failure undergoing living-donor kidney transplantation and in 80 controls, Results. CKD patients showed higher AGEs and esRAGE, lower AGEs/sRAGE ratios, and reduced MDPs. AGEs correlated positively with sRAGE, cRAGE, and HN, while MOTS-c was inversely associated with AGEs and the AGEs/sRAGE ratio. In multivariable analyses, HN remained independently associated with AGEs, sRAGE, and the AGEs/sRAGE ratio, whereas MOTS-c showed an inverse association with the AGEs/sRAGE ratio. CRP was associated with the AGEs/sRAGE ratio while PEW showed no associations with AGEs–RAGE components or MDP. Conclusions. CKD is characterized by increased glycoxidative stress and reduced MDPs, reflecting altered mitochondrial stress signaling. AGEs–RAGE and MDPs are biologically linked, suggesting partially overlapping but distinct pathophysiological pathways. Full article

Background/Objectives: The acute kidney injury (AKI) to chronic kidney disease (CKD) transition has been associated with a failed-repair proximal tubule (FR-PT) cell state. Hyperuricemia is an established CKD risk factor, but whether FR-PT cells have a coordinated metabolic signature reproducibly detectable across mouse models and human kidney disease remains unresolved. Methods: We assembled a pre-registered meta-analysis of 16 public mouse-kidney metabolomic cohorts (383 samples; five model classes; three injury phases) through a three-path harmonization pipeline. Convergent validation drew on KPMP single-nucleus RNA-seq (78,480 proximal tubule cells), two-sample Mendelian randomization of serum urate (102 instruments) against AKI/CKD/eGFR GWAS, and cross-cohort human plasma metabolomics across 2058 CKD/DKD patients. Results: Mouse meta-analysis identified uric acid (g = +2.70) and AICAR (g = +1.50) as the only cross-class conserved metabolites, with uric acid peaking during the AKI-to-CKD transition and returning to baseline in mouse CKD due to uricase clearance. Cross-class overlap between model classes was low (mean pairwise Jaccard = 0.109, below the pre-registered 0.20 threshold), invoking the pre-registered M-S1 stop rule: model-specific metabolic responses dominate, and the conserved signal is a small two-metabolite core superimposed on these largely model-specific programs. KPMP failed-repair PT cells exhibited transcriptional patterns consistent with coordinated four-arm purine-pathway dysregulation (de novo synthesis ↑, AMPK ↑, MOCOS ↑, URAT1 ↓), with this transcriptional pattern observed in both AKI and CKD donors (Spearman ρ = +0.900). Mendelian randomization was consistent with a possible causal contribution of serum urate to AKI/CKD/eGFR risk, with colocalization evidence at GCKR (PP.H4 = 1.000). Cross-cohort human plasma profiling across 2058 patients confirmed the systemic detectability of 29 purine-pathway metabolites in uricase-deficient humans (a translational-plausibility check, not validation of cellular source). Conclusions: The integrated data support a model in which FR-PT-associated purine-pathway reprogramming may contribute to the elevated urate signal observed during AKI-to-CKD transition, with uric acid as the candidate metabolic readout. Differences in uricase activity between mice and humans may help explain why chronic-phase urate signals are attenuated in mice but persist in humans. This work nominates a candidate cell-state metabolic readout of the AKI-to-CKD transition as a hypothesis for prospective testing; it does not establish causation, and therapeutic translation would require dedicated interventional studies. Full article

Chronic kidney disease (CKD) is a global health disease that must be recognized and monitored early to prevent major consequences and improve the health of patients, yet modern gradient boosting algorithms often produce dangerous false positives due to overconfidence and static ensemble weighting. To address this, we propose the Hyper-Fidelity Dynamic Ensemble framework for CKD diagnosis (HFDE–CKD). Our approach utilizes a rigid quad-fold data isolation protocol and applies Standard SMOTE to the training manifold. By removing direct diagnostic identifiers (e.g., eGFR, creatinine, and albumin), the framework is forced to rely on underlying early indications. We quantify predictive doubt using Shannon entropy and inter-model variance, concatenating these measurements with calibrated probability vectors into a multidimensional uncertainty matrix optimized via a logistic meta-learner. Evaluated on an imbalanced dataset of 11,933 records, HFDE–CKD achieved an accuracy of $0.8596$, a sensitivity of $0.8900$, and an F1-score of $0.8979$. Furthermore, HFDE–CKD’s superiority over the best-performing baseline was confirmed through McNemar’s test, which was statistically significant ($p<0.001$). Emphasizing diagnostic safety, the model yielded a Brier score of $0.1012$, an NLL of $0.3225$, and a specificity of $0.7907$, significantly reducing the risk of false positives. Furthermore, ablation testing confirmed the advantage of uncertainty injection, while SHAP analysis validated clinical dependency on early metabolic biomarkers. The proposed HFDE–CKD framework systematically leverages epistemic uncertainty to bypass the traditional sensitivity-versus-false-positive trade-off, providing a precisely calibrated, robust decision-support tool for early CKD screening. Full article

Chronic kidney disease (CKD) is a major public health challenge associated with substantial physical, psychological, social, and economic consequences. Although its clinical outcomes have been extensively investigated, less is known about how individuals progressively reconstruct their lives while living with an irreversible condition requiring long-term dialysis, particularly in contexts characterized by health inequities. This study aimed to develop a substantive theory explaining how adults reconstruct their lives while living with CKD on dialysis. A qualitative study was conducted using Strauss and Corbin’s Grounded Theory methodology. Eighteen adults receiving hemodialysis or peritoneal dialysis in Chile participated in semi-structured interviews. Data collection and analysis were conducted concurrently using theoretical sampling, the constant comparative method, memo writing, and theoretical saturation. The findings identified “Reconstructing Life While Living with Chronic Kidney Disease” as the central phenomenon. Life reconstruction emerged as a dynamic and ongoing process sustained by the interaction between resignation and survival and facilitated by three interrelated conditions: understanding the disease, social support networks, and nursing care. Through this process, participants progressively reorganized their identities, everyday lives, interpersonal relationships, and future life projects while living with an irreversible chronic condition. The resulting substantive theory provides a contextually grounded explanation of life reconstruction that integrates individual, relational, and social dimensions of living with CKD. By demonstrating that opportunities for life reconstruction are shaped not only by individual agency but also by supportive social and healthcare conditions, the findings contribute to nursing knowledge and provide a conceptual foundation for person-centered care, health equity, and future research on chronic illness. Full article

Background/Objectives: Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) is a frequent complication of chronic kidney disease, characterized by altered bone mineral density and mineral–hormonal metabolism. Therapeutic exercise may help attenuate these alterations, but evidence remains limited. This systematic review and meta-analysis evaluated the effects of therapeutic exercise on bone mineral density and mineral–bone and hormonal biomarkers in adults with CKD, focusing on CKD-MBD-related outcomes. Methods: Following a PROSPERO-registered protocol (CRD420251245021), Scopus, PubMed, Cochrane Central Register of Controlled Trials CENTRAL, and Web of Science were searched from inception to January 2026. Randomized controlled trials, including pilot randomized controlled trials, comparing therapeutic exercise with usual care or non-exercise control conditions in adults with CKD were included. Methodological quality and risk of bias were assessed with the PEDro scale and RoB 2, respectively. Results: Six studies involving 398 participants were included. Most interventions lasted 22 to 24 weeks and used resistance or combined aerobic and resistance exercise across inpatient and outpatient settings. Qualitative synthesis suggested improvements in femoral neck and lumbar spine bone mineral density and favorable biomarker changes. The assessed outcomes included femoral neck and lumbar spine BMD, calcium, phosphorus, sclerostin, PTH, FGF23, and klotho. Meta-analysis showed significant effects favoring therapeutic exercise for bone mineral density (MD = 0.05; 95% CI: 0.03 to 0.06; p < 0.00001; I² = 39%), mineral and bone-related biomarkers (SMD = 0.71; 95% CI: 0.42 to 0.99; p < 0.00001; I² = 75%), and hormonal biomarkers (SMD = 1.32; 95% CI: 0.88 to 1.77; p < 0.00001; I² = 85%). Conclusions: Therapeutic exercise may have beneficial effects on bone mineral density and selected mineral and hormonal biomarkers in adults with CKD. However, confidence in these findings is limited by the small number of studies, differences in CKD stage and exercise protocols, methodological limitations, risk of bias, and substantial heterogeneity in several pooled analyses. No definitive conclusions can currently be drawn regarding the optimal exercise modality, dose, or effects across CKD stages. Full article

Background: Uncertainty persists regarding the dose–response association between exercise exposure and blood pressure (BP) control in chronic kidney disease (CKD). This dose–response network meta-analysis examined whether different exercise modalities and model-estimated metabolic-equivalent exposure levels were associated with changes in systolic BP (SBP) and diastolic BP (DBP). Methods: Exercise dose was estimated as metabolic equivalents of task minutes per week (MET-min/week) from reported session duration, frequency, and intensity. Primary outcomes were changes in SBP and DBP, with exploratory subgroup analyses by dialysis status, baseline BP, and intervention duration. Results: The analysis included 26 randomized controlled trials (1218 participants). Aerobic exercise was associated with lower SBP, with the greatest model-estimated reduction at 880 MET-min/week (MD, −7.73 mm Hg). Resistance and mind–body exercise also showed model-estimated reductions, whereas combined aerobic-resistance training was not statistically significant. Dose–response estimates differed by dialysis status and intervention length, but several subgroup estimates were based on sparse data and wide uncertainty. Evidence certainty ranged from very low to high (CINeMA). Conclusions: Exercise interventions may be associated with BP reduction in CKD, but the identified MET-min/week ranges should be interpreted as exploratory, model-derived estimates rather than validated therapeutic thresholds. Better reported randomized trials are needed to confirm dose ranges, safety, adherence, and tolerability in dialysis and non-dialysis CKD populations. Full article

In recent years, interest in machine learning applications has grown rapidly, particularly in the medical domain, where large amounts of data are available for training these models. This review focuses on the potential of machine learning for early diagnosis and prognosis of chronic kidney disease (CKD) by examining the most recent literature. Articles published from 2016 to 2025 were collected from online databases such as PubMed, Web of Science, and Embase. After abstract and full-text screening, 57 articles were included in the results section. Machine learning was applied to clinical and laboratory data, medical imaging, urine samples, retinal images, and at-home measurements to diagnose CKD and predict CKD progression and related complications. Although many studies reported high discriminatory performance, the evidence base was dominated by retrospective, single-center, and methodologically heterogeneous studies, with frequent high-risk-of-bias findings and limited external validation. Although machine learning has been applied to a broad range of diagnostic and prognostic tasks in CKD, the current evidence is dominated by retrospective, single-center, and methodologically heterogeneous studies with a high risk of bias and limited external validation. Furthermore, most published models are not yet sufficiently validated for clinical deployment. Before these tools can be adopted in routine care, prospective, multicenter studies are required that report calibration and clinical utility, adhere to established reporting standards, and demonstrate added value over the current standard of care. Full article

Background: Cetuximab-based therapies continue to play an important role in the management of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) despite the increasing use of immunotherapy. However, data regarding treatment outcomes and prognostic factors remain limited. This study aimed to evaluate treatment outcomes and prognostic factors associated with survival in patients with R/M HNSCC treated with cetuximab-based regimens. Methods: This retrospective single-center cohort study included patients with recurrent/metastatic HNSCC who received cetuximab-based systemic therapy at the Department of Medical Oncology, Manisa Celal Bayar University Faculty of Medicine, between May 2012 and September 2025. Demographic, clinical, laboratory, and PET/CT data were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with survival were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Results: A total of 57 patients were included in the study. The median age was 65 years, and 91.2% of patients were male. Most patients had ECOG performance status 0–1 (94.7%) and stage IV disease (71.9%). The larynx was the most common primary tumor site (50.9%), while distant lymph node metastasis (63.2%) and lung metastasis (61.4%) were the predominant metastatic sites. Median PFS and OS were 4.6 months and 13.8 months, respectively. Kaplan–Meier analysis demonstrated that patients with a body mass index (BMI) > 25 had longer OS, whereas chronic kidney disease (CKD), primary tumor localization, and best response to first-line treatment were significantly associated with survival. In multivariable Cox regression analysis, chronic kidney disease (CKD) (HR: 5.15, p = 0.004), oral cavity primary tumor localization (HR: 2.55, p = 0.013), progressive disease as the best response to first-line treatment (HR: 4.44, p < 0.001) and the absence of grade 1–2 cetuximab-related dermatologic toxicity (HR: 3.20, p = 0.027) remained independent adverse prognostic factors. BMI was not independently associated with survival in multivariable analysis. Conclusions: Cetuximab-based therapy demonstrated clinically meaningful activity in patients with R/M HNSCC. Comorbidities, primary tumor localization, the absence of grade 1–2 cetuximab-related dermatologic toxicity and treatment response appear to substantially influence survival outcomes. Larger prospective studies are warranted to validate these findings. Full article

Background: Despite the increased infection-related morbidity of patients with chronic kidney disease (CKD), their vaccination coverage is low. Cocooning strategy has not been adequately researched in this group. Our aim was to evaluate vaccination coverage of CKD pediatric and adult patients and their families. Methods: In this prospective, single-center study, we recorded the vaccination coverage of CKD pediatric and adult patients and their families who attend a tertiary University Hospital. Vaccination rates were calculated according to the national vaccination program. Vaccination of pediatric CKD patients was compared to a control group of healthy children. Results: The vaccination rate of 63 hemodialysis patients was low for influenza (61.9%), COVID-19 (79.4% primary, 3.2% booster doses), RSV (50%), herpes zoster (42.4%), hepatitis B (41.3%), Streptococcus pneumoniae (25.4%), tetanus–pertussis (3.2%), and HPV (0%). Their 30 underaged relatives had low vaccination rates for influenza (13.3%), DTaP/Tdap (80%), and Men B (50%), with adequate vaccination for other pathogens. The 53 children with CKD were poorly vaccinated for influenza (20.8%), COVID-19 (0%), Streptococcus pneumoniae (15.4%), Men B (30.2%), DTaP/Tdap (67.9%), MMR (78.8%) and VZV (86.5%), but their vaccination rates for influenza were significantly higher compared to controls. Their 108 adult relatives were inadequately vaccinated for influenza (27.8%), COVID-19 (1.9%), and Tdap (1.9%). Their 35 underaged relatives were poorly vaccinated for influenza (22.9%) and DTaP (80%). Conclusions: Vaccination coverage of CKD patients is suboptimal for vaccines particularly important for their condition and their family members are insufficiently informed about potential contribution to their protection by cocooning strategy. Full article

Background and Objectives: Sarcopenia is highly prevalent among older adults with chronic kidney disease (CKD) and is associated with adverse clinical outcomes. The finger-ring (Yubi-wakka) test is a simple anthropometric screening tool based on calf circumference; however, its performance in older adults with CKD remains unclear. This study aimed to investigate the association of the finger-ring test with low muscle mass, sarcopenia, and comprehensive geriatric assessment parameters and to evaluate its diagnostic performance for identifying low muscle mass in older adults with CKD. Materials and Methods: This cross-sectional study included 115 patients aged ≥65 years with CKD who were evaluated in geriatric and nephrology inpatient services. After excluding two participants with missing finger-ring measurements, 113 individuals were analyzed. Muscle mass was assessed using bioelectrical impedance analysis and low muscle mass was defined according to EWGSOP2-based Turkish cut-off values. Demographic characteristics, anthropometric measurements, laboratory findings, and comprehensive geriatric assessment parameters were recorded. Correlation analyses, logistic regression models, receiver operating characteristic (ROC) analyses, and likelihood-ratio tests were performed. Results: Among 113 participants, 62 were classified as finger-ring positive (FR = 0) and 51 as finger-ring negative (FR = 1). Low muscle mass was significantly more frequent in the FR = 0 group than in the FR = 1 group (51.6% vs. 24.0%, p = 0.005). Finger-ring test results showed strong correlations with calf circumference (rho = 0.689, p < 0.001) and body mass index (BMI) (rho = 0.631, p < 0.001), whereas the correlation with muscle mass was modest (rho = 0.250, p = 0.008). For detecting low muscle mass, the finger-ring test demonstrated an area under the curve (AUC) of 0.643 (95% CI 0.554–0.732), sensitivity of 72.7%, specificity of 55.9%, positive predictive value of 51.6%, and negative predictive value of 76.0%. In multivariable analyses, BMI remained the strongest independent determinant of finger-ring test results, whereas the association with muscle mass lost statistical significance after BMI adjustment. Adding age and sex significantly improved discrimination, while the contribution of nutritional status was limited. Conclusions: The finger-ring test is associated with low muscle mass in older adults with CKD; however, its diagnostic performance is modest and appears to be substantially influenced by body size and calf circumference. Therefore, the finger-ring test should be considered a simple adjunctive screening tool rather than a stand-alone method for identifying low muscle mass in this population. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of pediatric chronic kidney disease (CKD) and comprise a heterogeneous group of developmental disorders with a substantial genetic contribution. Advances in next-generation sequencing have facilitated the identification of numerous candidate genes and rare variants associated with CAKUT. However, establishing causality and defining the biological functions of implicated genes remain major challenges. Functional validation is therefore essential to bridge the gap between gene discovery and mechanistic understanding, enabling the interpretation of genetic variation within the context of kidney development and disease. The zebrafish (Danio rerio) has emerged as a powerful in vivo model for studying renal development and interrogating the function of CAKUT-associated genes. Its utility stems from a high degree of genetic and developmental conservation with humans, conserved nephrogenic pathways, optical transparency during embryogenesis, and the relative ease of genetic manipulation. In this review, we provide an overview of zebrafish kidney development within the broader context of vertebrate nephrogenesis, highlighting the key genetic programs governing intermediate mesoderm specification, nephron segmentation, and pronephric morphogenesis. We then systematically examine CAKUT-associated genes that have been modeled in zebrafish, focusing on studies that have linked genetic perturbations to renal development and structural phenotypes. Finally, we discuss the strengths and limitations of zebrafish models for functional genomics and variant interpretation and consider their emerging role in bridging genetic discovery with mechanistic insights into CAKUT pathogenesis. Full article

Background: Chronic kidney disease (CKD) is a major global health burden, affecting more than 850 million people worldwide. Increasing evidence implicates engulfment and cell motility 1 (ELMO1), a cytoplasmic adaptor protein that regulates cytoskeletal remodeling, phagocytosis, and immune responses through the ELMO1–DOCK1–Rac1 signaling axis, in renal injury and disease progression. Methods: This narrative review identified relevant publications through searches of PubMed, Web of Science, and Google Scholar using combinations of the terms “ELMO1,” “kidney disease,” “diabetic kidney disease,” “IgA nephropathy,” “focal segmental glomerulosclerosis,” “acute kidney injury,” and “renal fibrosis.” English-language original research articles, genetic association studies, mechanistic investigations, and selected review articles were preferentially included according to their relevance to ELMO1 in kidney diseases. Results: Genetic association studies have implicated the ELMO1 locus in susceptibility to diabetic kidney disease (DKD), although associated variants and effect sizes differ across populations. Experimental studies suggest that ELMO1 regulates cytoskeletal remodeling, inflammatory responses, oxidative stress, and extracellular matrix deposition through the canonical ELMO1–DOCK1–Rac1 signaling pathway as well as Rac1-independent mechanisms. Available evidence supports a role for ELMO1 in DKD and renal fibrotic remodeling. In focal segmental glomerulosclerosis, the relevance of ELMO1 is primarily inferred from Rac1-associated podocyte injury pathways, whereas evidence in acute kidney injury remains limited and context-dependent. ELMO1 may contribute to inflammatory injury in ischemia–reperfusion settings but may also support efferocytosis and tissue repair in nephrotoxic injury models. In IgA nephropathy, evidence for a direct role of ELMO1 remains limited and is currently based largely on indirect mechanistic observations involving mucosal immunity and glomerular injury responses. Conclusions: ELMO1 is a context-dependent regulator of cytoskeletal, inflammatory, oxidative, and matrix-remodeling processes relevant to kidney disease. The strongest evidence currently supports its involvement in DKD, whereas its roles in other kidney diseases remain to be further defined in disease-specific, cell-type-specific, and stage-specific experimental models. Further studies are required to clarify its potential as a biomarker or therapeutic target in CKD. Full article

Chronic kidney disease (CKD) is a major public health problem worldwide, affecting over 10% of the global population, and its prevalence continues to increase. In addition to classic comorbidities, including cardiovascular and metabolic disorders, cognitive impairment (CI) has recently been recognized as a serious complication of CKD. CI can be observed across the entire spectrum of CKD, from G1 to G5 stages, independent of age-related changes. The kidney–brain axis seems to provide a conceptual framework in which microvascular disease, blood–brain barrier disruption, uremic toxins, oxidative stress, systemic inflammation, and consequent neuroinflammation converge to promote CI. This narrative review aims to synthesize the existing evidence on stage-dependent molecular mechanisms of CI in CKD, integrating clinical observations with proposed molecular and pathophysiological mechanisms. Because most studies investigating CI in CKD rely primarily on eGFR-based staging, our analysis was structured around GFR categories, assessing early-to-moderate CKD, defined according to KDIGO as G1–G3 stages, advanced CKD stages, including G4–G5 not yet requiring kidney replacement therapies, and kidney failure treated with different modalities of kidney replacement therapy, such as peritoneal dialysis, hemodialysis, and kidney transplantation. In addition to clinical observations and the burden of CI in CKD, we describe the potential stage-dependent pathomechanisms underlying vascular-executive, uremic-toxic, inflammatory, dialysis-hemodynamic, and post-transplant medication-related profiles as a continuum of cognitive disorders in individuals with CKD. Full article

Background: Pregnancy-associated plasma protein-A (PAPP-A)-derived N- and C-terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) are released from vulnerable atherosclerotic plaques. This study investigated the prognostic value of PAPP-A and IGFBP-4 fragments in patients with acute myocardial infarction (AMI), especially in those combined with chronic kidney disease (CKD). Methods: This prospective study measured admission levels of PAPP-A, NT- and CT-IGFBP-4 in 341 consecutive AMI patients. Of these patients, 232 were diagnosed with CKD (AMI and CKD), which consisted predominantly of early-stage cases. The primary outcome was one-year major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiovascular death, non-fatal MI, and stroke. Results: In the whole AMI cohort and the AMI and CKD subgroup, serum PAPP-A and NT-IGFBP-4 levels in patients with MACCE were both significantly higher than those in patients without MACCE, whereas CT-IGFBP-4 levels were similar. Multivariable Cox regression analysis revealed that increased levels of PAPP-A (HR, 2.48; 95% CI, 1.09–5.63; p = 0.030) and NT-IGFBP-4 (HR, 2.48; 95% CI, 1.03–6.02; p = 0.044) were associated with MACCE in the whole AMI cohort. The areas under the receiver operating characteristic (ROC) curve for PAPP-A and NT-IGFBP-4 were 0.637 and 0.633, respectively. However, in the AMI and CKD subgroups, only NT-IGFBP-4 was identified as an independent predictor of MACCE (HR, 2.72; 95% CI, 1.16–6.41; p = 0.021) and cardiovascular death (HR, 2.63; 95% CI, 1.01–6.84; p = 0.048). Conclusions: PAPP-A and NT-IGFBP-4 were independently associated with one-year MACCE. NT-IGFBP-4 may be a promising prognostic marker in AMI patients with early-stage CKD. Full article