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To our knowledge, there are no studies on advanced chronic kidney disease (CKD) analysing the impact of ageing on serum concentrations of uraemic toxins while adjusting for renal function. Knowledge of this feature, however, could influence prognostic assessment and therapeutic decision-making, e.g. about when to start dialysis or how intensive it should be. Indeed, the slowing down of metabolism with age may result in lower uraemic toxin concentrations, hence reducing their toxic effects. In this case, a later start of dialysis or less intensive dialysis may become justified in an already fragile population that might enjoy a better quality of life without a survival disadvantage with conservative treatment. We assessed the impact of advancing age on uraemic solute concentrations [blood, urea, nitrogen (BUN), uric acid, creatinine, asymmetric and symmetric dimethylarginine (ADMA and SDMA), β 2 -microglobulin and a large array of protein-bound solutes] by matching 126 maintenance haemodialysis patients subdivided into two age-groups, younger vs. older (using the median as cut-off: 72 years). Concentrations were compared after age stratification and were matched with patient and dialysis characteristics. In addition, 93 non-dialysed CKD patients (median as cut-off: 70 years), with a comparable average estimated glomerular filtration rate (eGFR) between younger and older age-groups, were analysed. In haemodialysis patients, carboxy-methyl-furanpropionic acid (CMPF) levels were markedly higher and BUN and uric acid borderline lower in the older age-group. All other solutes showed no difference. At multifactor analysis, the concentration of several uraemic toxins was associated with residual renal function and protein intake in the overall haemodialysis group and the younger group, but the association with most solutes, especially those protein-bound, was lost in the older age-group. No differences were found in non-dialysed CKD patients. It was concluded that in this CKD population concentrations of uraemic toxins did not change substantially with calendar age.

Objective： This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin （β2M）, a conservative immune molecule in vertebrate.Data Sources： The data used in this review were obtained from PubMed up to October 2015.Terms of β2M, immune response, and infection were used in the search.Study Selections： Articles related to β2M were retrieved and reviewed.Articles focusing on the characteristic and function of β2M were selected.The exclusion criteria of articles were that the studies on β2M-related molecules.Results： β2M is critical for the immune surveillance and modulation in vertebrate animals.The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases.β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies.It also involves in forming major histocompatibility complex （MHC class Ⅰ or MHC Ⅰ） or like heterodimers, covering from antigen presentation to immune homeostasis.Conclusions： Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools.Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.

Recent studies suggest that high-dose hemodiafiltration (HDF) may reduce mortality more effectively than high-flux hemodialysis (HD), though the mechanisms remain unclear. Traditional metrics such as Kt/V and convective volume do not fully capture overall dialysis efficiency. This study proposes a novel approach using circulating beta-2-microglobulin (ß2M) levels to estimate an equivalent Continuous Dialytic Clearance (eCDC ß2M ), reflecting an equivalent glomerular filtration rate. Using data from the FRENCHIE study, we calculated eCDC ß2M and assessed its association with patient outcomes, including all-cause and cardiovascular mortality, in comparison with traditional dialysis dose metrics. Our analysis showed that HDF achieved higher treatment efficiency than high-flux HD, with a mean increase of + 1.5 ml/min in eCDC ß2M . Moreover, eCDC ß2M demonstrated superior predictive value for mortality risk compared to Kt/V. These findings support eCDC ß2M as a meaningful and physiologically relevant measure of dialysis efficiency and adequacy. By better reflecting the continuous function of the native kidney, this approach may improve patient stratification and outcome prediction across all forms of kidney replacement treatment schedule. Further validation in independent patient cohorts is warranted.

The number of patients with chronic kidney disease increases while the number of available donor organs stays at approximately the same level. Unavoidable accumulation of the uremic toxins and cytokines for these patients comes as the result of malfunctioning kidneys and their high levels in the blood result in high morbidity and mortality. Unfortunately, the existing methods, like hemodialysis and hemofiltration, provide only partial removal of uremic toxins and/or cytokines from patients’ blood. Consequently, there is an increasing need for the development of the extracorporeal treatments which will enable removal of broad spectrum of uremic toxins that are usually removed by healthy kidneys. Therefore, in this work we developed and tested ordered mesoporous carbons as new sorbents with dual porosity (micro/meso) that provide selective and efficient removal of a broad range of uremic toxins from human plasma. The new sorbents, CMK-3 are developed by nanocasting methods and have two distinct pore domains, i.e. micropores and mesopores, therefore show high adsorption capacity towards small water soluble toxins (creatinine), protein-bound molecules (indoxyl sulfate and hippuric acid), middle molecules (β-2-microglobulin) and cytokines of different size (IL-6 and IL-8). Our results show that small amounts of CMK-3 could provide selective and complete blood purification.

To analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sjögren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment. Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the \"Assessment of Systemic Signs and Evolution of Sjögren's Syndrome\" (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Patient median age was 58 (25(th)-75(th): 51-67) and median disease duration was 5 (2-9) years. Median ESSDAI at enrollment was 2 (0-7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]-[11] vs 2 [0-7], P = 0.03; 4 [1]-[11] vs 2 [0-7], P< 0.0001); 4 [2]-[10] vs 2 [0-6.6], P< 0.0001 and 4 [2-8.2] vs 2 [0-7.0], P = 0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1-3665.5) vs 898.9 (715.9-1187.2) pg/ml, P = 0.01 and 2.6 (2.2-2.9) vs 2.1 (1.8-2.6) mg/l, P = 0.04, respectively). In pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity.

IntroductionSjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the exocrine glands. Carpal tunnel syndrome (CTS) is suggested to be more frequent among SS patients than in the general population. The aim of this study was to seek associations between the CTS and the laboratory and clinical findings of SS patients.MethodsFifty patients diagnosed with primary SS (pSS) were examined. Clinical evaluation by a rheumatologist and electrophysiological studies were conducted. Data on laboratory tests results was collected. Control group consisted of 50 sex and age-matched individuals with osteoarthritis (OA).ResultsOut of 50 patients in the study group 27 (54%) were diagnosed with CTS. The prevalence of CTS among 50 individuals in the control group was 8%. Among pSS patients with CTS the joint involvement was not more common than in those from the non-CTS group [15 vs. 13 (p = 0.945)]. There was an expected difference in sleep disorders [18 vs. 9 (p = 0.012)] and paresthesia [23 vs. 13 (p = 0.024)]. The major finding was a significant difference in elevated beta2-microglobulin (B2MG) [23 vs. 13 (p = 0.024)]. Other studied factors, suggested in the literature as significant in the pSS-related neuropathy, were not statistically different between the groups.ConclusionOur study confirms that CTS is more prevalent among pSS patients than in the general population and suggests that a new approach is required towards the pathogenesis of this phenomenon. We hypothesize that CTS is more associated with an overall disease activity than joint involvement as such.

Online hemodiafiltration (OL-HDF), the most efficient renal replacement therapy, enables enhanced removal of small and large uremic toxins by combining diffusive and convective solute transport. Randomized controlled trials on prevalent chronic kidney disease (CKD) patients showed improved patient survival with high-volume OL-HDF, underlining the effect of convection volume (CV). This retrospective international study was conducted in a large cohort of incident CKD patients to determine the CV threshold and range associated with survival advantage. Data were extracted from a cohort of adult CKD patients treated by post-dilution OL-HDF over a 101-month period. In total, 2293 patients with a minimum of 2 years of follow-up were analyzed using advanced statistical tools, including cubic spline analyses for determination of the CV range over which a survival increase was observed. The relative survival rate of OL-HDF patients, adjusted for age, gender, comorbidities, vascular access, albumin, C-reactive protein, and dialysis dose, was found to increase at about 55l/week of CV and to stay increased up to about 75l/week. Similar analysis of pre-dialysis p2-microglobin (marker of middle-molecule uremic toxins) concentrations found a nearly linear decrease in marker concentration as CV increased from 40 to 75l/week. Analysis of log C-reactive protein levels showed a decrease over the same CV range. Thus, a convection dose target based on convection volume should be considered and needs to be confirmed by prospective trials as a new determinant of dialysis adequacy.

Introduction: Variations in kidney injury molecule-1 (KIM-1) and beta2-microglobulin (β2MG) levels, both involved in the pathogenesis of systemic autoimmunity, have been linked to tubulointerstitial lesions in patients with systemic lupus erythematosus (SLE). However, the significance of KIM-1 and β2MG in the pathogenesis and development of extrarenal manifestations in SLE remains unclear. This study aims to investigate the relationship between KIM-1 and β2MG levels, measured in both serum and urine, and their association with the clinical and biological features of SLE. Materials and Methods: KIM-1 and β2MG levels were measured in 80 adult patients with SLE (who exhibited mucocutaneous, hematological, and renal manifestations) and 30 control subjects. All patients with renal abnormalities related to SLE underwent a renal biopsy. The serum and urinary levels of KIM-1 (measured in pg/mL for serum and ng/mL for urine) and β2MG (measured in ng/dl for serum and mg/l for urine) were determined for each subject using the ELISA method and immunoturbidimetry, respectively. Results: There were significant differences in the serum and urinary levels of KIM-1 and β2MG between the SLE group and the control group, as well as among subgroups with different manifestations (renal, cutaneous, and hematological). Elevated levels of KIM-1 and β2MG, in both serum and urine, were associated with the clinical activity of the disease, the inflammatory process, and the development of tissue damage in various organs, leading to declines in renal function, hematological disorders, and mucocutaneous manifestations. Conclusions: KIM-1 may play a pathogenic role in kidney injury and disease, while β2MG could have a pathogenic role in both kidney and non-kidney diseases. In summary, KIM-1 characterizes renal involvement, while serum β2MG correlates with the progression of cumulative lesions in SLE patients. Our findings could enhance early diagnosis, predict disease progression, and elucidate the pathogenic mechanisms underlying SLE.

Radiotherapy serves as a crucial therapeutic modality for esophageal squamous cell carcinoma (ESCC). Beyond its role in tumor growth control, radiotherapy also exerts immunomodulatory effects on tumors and their microenvironment. This study investigates the potential impact of radiation on human leukocyte antigen class I (HLA-I) and the underlying mechanisms of tumor immunity. Changes in peripheral blood β2-microglobulin (β2M) levels were assessed pre- and post-radiotherapy. ESCC cells were subjected to radiation, and the expression of HLA-I was evaluated using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Differential gene expression analysis was conducted utilizing The Cancer Genome Atlas (TCGA) and transcriptome sequencing to explore the molecular mechanisms by which radiation may influence HLA-I expression. Interferon-gamma (IFN-γ) was identified as a central regulator of HLA-I expression by STRING database. ESCC cell lines were co-cultured with immune cells, following radiation exposure, the levels of secreted IFN-γ in the culture medium were quantified. Changes in T cells and dendritic cells (DCs) were detected via immunofluorescence. The study found that elevated β2M expression in peripheral blood cells of patients with ESCC was significantly associated with improved Disease-Free Survival (DFS). Radiation treatment was observed to enhance the expression of HLA-I in ESCC cells. Analysis of TCGA data and gene transcriptome sequencing identified the cytokine-cytokine receptor interaction as the most enriched pathway. IFN-γ was identified as the central cytokine in regulating HLA-I expression, with the capability to induce its expression. When ESCC cells were co-cultured with immune cells and treated with radiation, there was an increase in IFN-γ concentration in the medium, accompanied by altered distributions of DCs and T cells. These findings suggest that radiation may influence immune cells through the modulation of IFN-γ.

Background β2‐Microglobulin (B2M) has garnered considerable interest as a potential pro‐ageing factor, leading to speculation about its involvement in muscle metabolism and the development of sarcopenia, a key component of ageing phenotypes. To explore this hypothesis, we conducted a comprehensive investigation into the impact of B2M on cellular and animal muscle biology, as well as its clinical implications concerning sarcopenia parameters in older individuals. Methods In vitro myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. For in vivo research, C57BL/6 mice aged 3 months were intraperitoneally given 250 μg of B2M daily, and muscular alterations were assessed one month later. Human blood samples were obtained from 158 participants who underwent assessments of muscle mass and function at an outpatient geriatric clinic affiliated with a teaching hospital. Sarcopenia and associated parameters were assessed using cut‐off values specifically tailored for the Asian population. The concentration of serum B2M was quantified through an enzyme‐linked immunosorbent assay. Results Recombinant B2M inhibited in vitro myogenesis by increasing intracellular reactive oxygen species (ROS) production. Furthermore, B2M significantly induced differential myotube atrophy via ROS‐mediated ITGB1 downregulation, leading to impaired activation of the FAK/AKT/ERK signalling cascade and enhanced nuclear translocation of FoxO transcription factors. Animal experiments showed that mice with systemic B2M treatment exhibited significantly smaller cross‐sectional area of tibialis anterior and soleus muscle, weaker grip strength, shorter grid hanging time, and decreased latency time to fall off the rotating rod, compared to untreated controls. In a clinical study, serum B2M levels were inversely associated with grip strength, usual gait speed and short physical performance battery (SPPB) total score after adjustment for age, sex, and body mass index, whereas sarcopenia phenotype score showed a positive association. Consistently, higher serum B2M levels were associated with higher risk for weak grip strength, slow gait speed, low SPPB total score, and poor physical performance. Conclusion These results provide experimental evidence that B2M exerted detrimental effects on muscle metabolism mainly by increasing oxidative stress. Furthermore, we made an effort to translate the results of in vitro and animal research into clinical implication and found that circulating B2M could be one of blood‐based biomarkers to assess poor muscle health in older adults.