Serum Syndecan-1 Levels Research Articles

Syndecan-1 in the Serum of Deceased Kidney Donors as a Potential Biomarker of Kidney Function.

The process of kidney transplantation remains the optimal treatment for end-stage renal disease, offering improved quality of life and increased survival rates compared to long-term dialysis. However, despite advances in surgical techniques, immunosuppression regimens, and post-operative care, there are still significant challenges in predicting the organ's status and long-term outcomes of transplantation. Among the many factors that influence graft survival, the quality of the donated organ plays a fundamental role. There is an ongoing need for accurate and reliable biomarkers. Syndecan-1 is found in the endothelial glycocalyx and shed at a higher rate into the blood during systemic pathological conditions. The aim of this study is to evaluate the potential of serum syndecan-1 levels as a biomarker for assessing donor kidney quality and to investigate its correlation with donor characteristics and short-term outcomes in kidney recipients. We investigated serum syndecan-1 levels in 80 deceased donors and correlated them with donor characteristics and short-term outcomes (defined as delayed graft function - defined as the need for dialysis within the first week post-transplantation and renal function at 3 months post-transplantation - assessed using serum creatinine levels) in 104 corresponding kidney recipients. This single-center retrospective observational cohort study was conducted from April to December 2021. The donor pool consisted of 65% males with a median age of 53 years. Of these, 45 donors (56%) were classified as extended criteria donors. Higher syndecan-1 levels correlated with the last creatinine levels before organ procurement (R = 0.32, p = 0.01) and were marginally higher in donors with acute kidney injury (p = 0.07). However, syndecan-1 levels were not associated with short-term outcomes in kidney recipients (renal function at 3 months). The data suggests syndecan-1 could be a potential biomarker for assessing donor kidney quality, although its implications on recipient outcomes require further study. This pilot investigation underscores the importance of syndecan-1 in evaluating organ quality but highlights the necessity for more extensive research to validate these findings and explore their implications in transplant success.

Serum levels of free light chains and syndecan-1 in patients with rheumatoid arthritis and systemic lupus erythematosus.

Systemic autoimmune rheumatic diseases (SARDs) are characterized by chronic inflammation. Reliable biomarkers are crucial for diagnosis, monitoring disease progression and therapeutic responses. This study explores serum Syndecan-1 (SDC-1) as a biomarker for these conditions and its relationship with free light chain (FLC) levels. A retrospective analysis was performed on sera from 60 patients with rheumatoid arthritis (RA) and from 60 with systemic lupus erythematosus (SLE), alongside 50 healthy donors (HD). Κ- and λ- FLCs were determined by turbidimetric assay, while SDC-1 levels by ELISA. Kruskal-Wallis test, Wilcoxon-Mann-Whitney U test, multivariable linear regression and Spearman's correlation were employed to compare biomarker levels across groups and to explore correlations. SDC-1, κ-FLC, and λ-FLC were significantly increased in RA and SLE patients compared with HD (p< 0.001), while no significant differences in the κ/λ ratio were observed among the groups (p= 0.4). A significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age or disease activity indices. Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared with HD underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cell activation, supporting the multifaceted role of SDC-1 in the pathogenesis of SARDs.

Elevated Serum Syndecan-1 Levels Are Associated with Obesity-Related Complications in Children

Background: Syndecan-1 plays a crucial role in cell differentiation, growth, adhesion, wound healing, and inflammatory processes. It has been linked to obesity, particularly overweight and chronic low-grade inflammation. Objectives: This study aimed to compare serum syndecan-1 levels between obese children and a healthy control group and to investigate the relationship between serum syndecan-1 levels and renal and cardiovascular complications associated with obesity in children. Methods: We assessed 30 obese and 30 healthy children aged 8 - 16 years. Blood samples were collected from both groups to measure serum aspartate aminotransferase (AST), syndecan-1, fasting blood glucose (FBG), alanine aminotransferase (ALT), creatinine, and urea concentrations. In the obese group, high-density lipoprotein cholesterol (HDL-C), insulin, triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels were also measured, along with homeostasis model assessment of insulin resistance (HOMA-IR). Results: The mean serum syndecan-1 levels in the obese and control groups were 15.65 ± 10.01 ng/mL and 6.99 ± 3.79 ng/mL, respectively, with a significantly higher level observed in the obese group (P &lt; 0.005). Significant differences were also found in BMI, BMI SDS, creatinine, AST, and ALT levels between the two groups (P &lt; 0.05), with all parameters being higher in the obese group. A significant positive linear association was identified between syndecan-1 levels and creatinine, TG, and BMI SDS (r = 0.711, r = 0.630, r = 0.682, P &lt; 0.01). Additionally, a strong negative correlation was found between syndecan-1 and HDL-C levels (r = -0.609, P &lt; 0.001). No significant linear relationship was detected between syndecan-1 levels and LDL-C, ALT, AST, glucose, urea, insulin levels, or HOMA-IR measurements (P &gt; 0.05). Linear regression analysis revealed that serum creatinine levels and BMI SDS were significantly linked to changes in syndecan-1 levels. Conclusions: Syndecan-1 is elevated in obese children due to inflammation and may serve as an early biomarker for endothelial damage. It can be useful in detecting obesity-related renal damage and cardiovascular risk in children.

Serum syndecan1 has the potential to reflect activity at diagnosis and predict death during follow-up in patients with ANCA-associated vasculitis

ObjectivesThis study investigated whether serum syndecan1 at diagnosis reflects activity at diagnosis and predicts poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).MethodsThe study included 79 patients with AAV from the cohort of Korean patients diagnosed with AAV. AAV-specific indices, including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), 36-item short-form survey (SF-36) physical and mental component summary (PCS and MCS), and vasculitis damage index (VDI), were assessed. Laboratory data including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also collected. The highest tertile and upper half of the BVAS were tentatively defined as having high AAV activity. Serum syndecan1 levels were measured in sera stored at diagnosis.ResultsSerum syndecan1 at diagnosis was significantly correlated with AAV activity and functional status, as assessed by BVAS, FFS, SF-36 PCS, MCS, and acute-phase reactants, including ESR and CRP. Patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis, and those with serum syndecan1 ≥ 60.0 ng/mL at diagnosis showed significantly higher risks for the highest tertile and the upper half of BVAS at diagnosis than those without, respectively. Patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis had a significantly higher risk for all-cause mortality during follow-up than those without, and further, exhibited a significantly lower cumulative patients’ survival rate than those without.ConclusionSerum syndecan1 at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.

Assessing the predictive value of elevated postoperative syndecan-1 levels for progressive acute kidney injury and kidney replacement therapy necessity in adult cardiac surgery patients

BackgroundThe development of acute kidney injury (AKI) post-cardiac surgery significantly increases patient morbidity and healthcare costs. Prior researches have established Syndecan-1 (SDC-1) as a potential biomarker for endothelial injury and subsequent acute kidney injury development. This study assessed whether postoperative SDC-1 levels could further predict AKI requiring kidney replacement therapy (AKI-KRT) and AKI progression.MethodsIn this prospective study, 122 adult cardiac surgery patients, who underwent valve or coronary artery bypass grafting (CABG) or a combination thereof and developed AKI within 48 h post-operation from May to September 2021, were monitored for the progression to stage 2–3 AKI or the need for KRT. We analyzed the predictive value of postoperative serum SDC-1 levels in relation to multiple endpoints.ResultsIn the study population, 110 patients (90.2%) underwent cardiopulmonary bypass, of which thirty received CABG or combined surgery. Fifteen patients (12.3%) required KRT, and thirty-eight (31.1%) developed progressive AKI, underscoring the severe AKI incidence. Multivariate logistic regression indicated that elevated SDC-1 levels were independent risk factors for progressive AKI (OR = 1.006) and AKI-KRT (OR = 1.011). The AUROC for SDC-1 levels in predicting AKI-KRT and AKI progression was 0.892 and 0.73, respectively, outperforming the inflammatory cytokines. Linear regression revealed a positive correlation between SDC-1 levels and both hospital (β = 0.014, p = 0.022) and ICU stays (β = 0.013, p < 0.001).ConclusionElevated postoperative SDC-1 levels significantly predict AKI progression and AKI-KRT in patients following cardiac surgery. The study’s findings support incorporating SDC-1 level monitoring into post-surgical care to improve early detection and intervention for severe AKI.

Syndecan-1 Levels in Females with Active Rheumatoid Arthritis.

Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71-93); specificity, 52% (95%CI: 31-72); positive predictive value, 78% (95%CI: 70-84); and negative predictive value, 62% (95%CI: 44-77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.

The β2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury.

Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β2-adrenergic receptor (β2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome. The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy. Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours. The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β2-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels. Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.

#220 Acute vascular response to hemodialysis as measured by serum syndecan-1 and endothelin-1 levels, as well as vascular stiffness

Abstract Background and Aims End-stage kidney disease (ESKD) patients on chronic hemodialysis (HD) have very high cardiovascular risk. Acute vascular changes during dialysis mediated partially by factors of the endothelium may have a crucial role in the cardiovascular (CV) disease of HD patients. Aim To study acute vascular changes during HD measured by applanation tonometry and to assess the role of syndecan-1 (SDC-1), endothelin-1 (ET-1), and traditional and non-traditional CV risk factors in these changes. Method 29 consecutive chronic HD patients (median age: 65.6 ± 10.4 years; 52% men) were included in the study. Pre-, mid-, and post-HD plasma SDC-1 and ET-1 levels and routine biochemical parameters were measured. Applanation tonometry (SphygmoCor, AtCor Medical) was performed before HD. Results As assessed by trend analysis, SDC-1 levels increased significantly during HD (p = 0.004). ET-1 levels were decreasing during HD. Male patients had significantly higher ET-1 levels than women. Patients were divided into 2 groups based on their pulse wave velocity (PWV): PWV ≥12 m/s and PWV &amp;lt;12 m/s. Pre-HD and mid-HD SDC-1 levels were significantly higher in the group with PWV ≥12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/ml, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/ml, p = 0.044, respectively). Post-HD ET-1 levels were significantly higher in the patient group having PWV ≥12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients having PWV ≥12 m/s had significantly higher pre-HD peripheral and aortic systolic blood pressure than the patients having lower PWV (147.4 ± 73.3 vs. 134.1 ± 72.2 mmHg, p = 0.038, and 130.7 ± 16.6 vs. 122.5 ± 14.9 mmHg, p = 0.016, respectively). Mid-HD and post-HD blood pressures were not different. We found a positive correlation between total cholesterol and the decrease in SDC-1 levels during HD (r = 0.539; p = 0.008). Pre-, mid-, and post-HD SDC-1 correlated significantly with the ultrafiltration volume during HD (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion SDC-1 and ET-1 may contribute to the vascular changes observed during HD, and they have correlations with some traditional and non-traditional CV risk factors.

Doxycycline protects against sepsis-induced endothelial glycocalyx shedding

Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the “backbone” of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment.

Association of Preoperative and Postoperative Plasma Syndecan-1 and Colorectal Cancer Outcome.

A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker. We analyzed SDC1 in the transcriptomic profiles of a major publicly available CRC cohort from The Cancer Genome Atlas (TCGA) using a computational algorithm. We investigated serum SDC1 levels preoperatively and on postoperative day seven in 48 patients with stage I-III CRC who underwent surgery during July-December 2019 at Gifu University Hospital. For TCGA, no significant differences existed between the high and low SDC1 expression groups regarding disease-free, disease-specific, and overall survival for stage I-III, and only overall survival for stage IV was significantly different. In our study, among the 48 patients, 17 (no recurrence), 13 (1 recurrence), and 18 (10 recurrences) had stage I-III, respectively. Preoperative and postoperative day 7 SDC1 levels for patients with stage I-III were 10.7±2.3 and 9.9±3.1 ng/ml (p=0.40), 11.1±1.7 and 10.1±0.8 ng/ml (p=0.07), and 10.3±2.0 and 9.5±1.4 ng/ml (p=0.15), respectively. In stage II and III, patients were divided into two groups according to differences between preoperative and postoperative SDC1 levels (SDC1pre-pro). SDC1pre-pro ≤0 group significantly prolonged disease-free survival compared with SDC1pre-pro >0 group (p=0.048). Dynamic change in serum SDC1 levels serves as a prognostic biomarker for stage II and III colorectal cancer.

Assessment of MMP-9 and clinical characteristics in dogs with tracheal collapse based on cough severity and fluoroscopic findings: a cross-sectional study

BackgroundTracheal collapse (TC), a common disease in dogs, is characterized by cough; however, little is known about the serum biomarkers that can objectively evaluate the severity of cough in canine TC. Furthermore, studies elucidating the relationship of fluoroscopic characteristics with the severity of cough are lacking. Therefore, this study aimed to evaluate the relationship between cough severity and clinical characteristics, fluoroscopic images, and new serum biomarkers in canine TC.ResultsFifty-one client-owned dogs diagnosed with TC based on fluoroscopic and clinical signs were enrolled in this study and divided into three groups according to the severity of cough (grade of cough: 0, 1, and 2). Signalments, comorbidities, and fluoroscopic characteristics were compared among the groups retrospectively. The serum matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), surfactant protein-A (SP-A), and syndecan-1 (SDC-1) levels were measured in all groups. No significant differences in age, breed, sex, or clinical history were observed among the groups. Concomitant pharyngeal collapse increased significantly with the severity of cough (p = .031). Based on the fluoroscopic characteristics, the TC grade of the carinal region increased significantly and consistently with the grade of cough (p = .03). The serum MMP-9 level was significantly higher in the grade 2 group than that in the grade 0 group (p = .014). The serum IL-6 level was significantly lower in the grade 1 group than that in the grade 0 group (p = .020). The serum SP-A and SDC-1 levels did not differ significantly among the groups.ConclusionsThe severity of cough with the progression of TC can be predicted with the fluoroscopic TC grade at the carinal region. MMP-9 may be used as an objective serum biomarker that represents cough severity to understand the pathogenesis.

Syndecan-1 as the Effect or Effector of the Endothelial Inflammatory Response?

IntroductionSyndecan-1 is a heparan sulfate proteoglycan found in the glycocalyx of vascular endothelial cells. Serum levels of syndecan-1 have repeatedly been demonstrated to increase following traumatic injury and shock, but it is unclear whether syndecan-1 plays an active role in the inflammatory response or is simply a biomarker of a state of hypoperfusion. The aim of this study was to identify the role of syndecan-1 role in the inflammatory process in the absence of trauma. MethodsMale mice were randomized into five groups (n = 3). Four groups received increasing concentrations of syndecan-1 (1, 10, 100, and 1000pg/mL per blood volume) and a fifth group was given normal saline as a control via intravenous injection. These concentrations were selected based on previous syndecan-1 enzyme-linked immunosorbent assay data acquired following induced hemorrhagic shock in mice resulting in serum levels of 10-6000 pg/mL. Mice from each group were sacrificed at 1-, 4-, and 24-h time points for serum biomarker evaluation. A multiplex enzyme-linked immunosorbent assay was performed to analyze proinflammatory cytokines and chemokines including interleukin (IL)-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemoattractant protein-1, TNF-α, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, and normal T cell expressed and presumably secreted levels. Whole blood was analyzed via rotational thromboelastometry in a separate group of mice dosed with syndecan-1 at 1000 pg/mL and compared to sham mice at 1 h. ResultsTumor necrosis factor-α was significantly elevated in the 1000 pg/mL group compared to sham animals. There were no significant changes in IL-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, monocyte chemoattractant protein--1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, or normal T cell expressed and presumably secretedat 1, 4, and 24 h for any group when compared to mice receiving saline alone. No significant differences were noted in coagulability between the 1000 pg/mL syndecan-1 group and shams at 1 h ConclusionsInflammatory cytokine concentrations did not change with increasing dosage of syndecan-1 within mice at any timepoint, except for an acute change in tumor necrosis factor-α which was transient. Based on our results, syndecan-1 appears to be a biomarker for inflammation rather than an active participant in eliciting an inflammatory response. Further research will focus on the role of syndecan-1 following hemorrhagic shock.

Acute Vascular Response to Hemodialysis as Measured by Serum Syndecan-1 and Endothelin-1 Levels as Well as Vascular Stiffness

Background: Chronic hemodialysis (HD) patients have a very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. The aim of this article is to study the acute vascular changes during HD. Methods: In 29 consecutive chronic HD patients (age: 65.6 ± 10.4 years), their pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. Results: Their SDC-1 levels increased during HD (p = 0.004). Males had higher ET-1 levels. The patients were divided into two groups based on their pre-HD pulse wave velocity (PWV): PWV ≥ 12 m/s and PWV &lt; 12 m/s. The pre-HD and mid-HD SDC-1 levels were higher in the group with a PWV ≥ 12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/mL, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/mL, p = 0.044, respectively). The post-HD ET-1 levels were higher in the patient group with a PWV ≥ 12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients with a PWV ≥ 12 m/s had higher pre-HD peripheral and aortic systolic blood pressures (p &lt; 0.05). The total cholesterol correlated with the SDC-1 decrease during HD (r = 0.539; p = 0.008). The pre-, mid-, and post-HD SDC-1 correlated with ultrafiltration (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion: SDC-1 and ET-1 contribute to the vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

Investigation of the relationship between intradialytic hypotension during hemodialysis and serum syndecan-1 concentration

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.

Predictive Value of Early Inflammatory Markers in Trauma Patients Based on Transfusion Status

IntroductionSeven key inflammatory biomarkers were recently found to be associated with the risk of mortality in a multicenter study of massively transfused patients. The aim of this prospective single-center study was to determine which of these early inflammatory markers could predict 30-d mortality among all critically injured trauma patients. MethodsSerum samples were collected at 6, 24, and 72 h from 238 consecutive patients admitted to the intensive care unit following traumatic injury. Inflammatory markers syndecan-1, eotaxin, IL-1ra, IL-6, IL-8, IL-10, IP-10, and MCP-1 were analyzed via multiplex enzyme-linked immunosorbent assay. Subgroup analysis was performed for patients undergoing massive transfusion (≥5 red blood cells), submassive transfusion (1-4 red blood cells), or no transfusion during the first 4 h postinjury. The primary outcome of 30-d survival was modeled as a function of each biomarker and confounders using repeat measures logistic regression. ResultsPatients had a median age of 51.3 y [33.7, 70.2], 70.6% were male, 17.4% experienced penetrating trauma, and had a median injury severity score of 22 [14, 33]. IL-1ra, IL-8, IL-10, and MCP-1 were significantly increased during the first 72 h in nonsurvivors (n = 31). Elevated IL-1ra, IL-8, IL-10, and MCP-1 at 6 h postinjury were associated with 30-d mortality. By contrast, serum syndecan-1 and eotaxin levels were not associated with mortality at any time point. IL-8 and lactate were increased at 6 h in 30-d nonsurvivors for patients receiving submassive transfusion (n = 78). ConclusionsEarly evaluations of IL-1ra, IL-8, IL-10, and IP-10 within 6 h of injury are useful predictors of 30-d mortality. Subgroup analysis suggests that transfusion status does not significantly affect early inflammatory markers. Level of EvidenceLevel III, prognostic/epidemiological.

Use of probiotics in patients with chronic kidney disease on hemodialysis: a randomized clinical trial.

Supplementation with probiotics for patients with chronic kidney disease (CKD) may be associated with decreased systemic inflammation. To assess the impact of oral supplementation with probiotics for patients with CKD on hemodialysis. This double-blind randomized clinical trial included 70 patients on hemodialysis; 32 were given oral supplementation with probiotics and 38 were in the placebo group. Blood samples were collected at the start of the study and patients were given oral supplementation with probiotics or placebo for three months. The probiotic supplement comprised four strains of encapsulated Gram-positive bacteria: Lactobacillus Plantarum A87, Lactobacillus rhamnosus, Bifidobacterium bifidum A218 and Bifidobacterium longum A101. Patients were given one capsule per day for 3 months. Blood samples were taken throughout the study to check for inflammatory biomarkers. Non-traditional biomarkers Syndecan-1, IFN-y, NGAL, and cystatin C were measured using an ELISA kit, along with biochemical parameters CRP, calcium, phosphorus, potassium, PTH, GPT, hematocrit, hemoglobin, glucose, and urea. Patients given supplementation with probiotics had significant decreases in serum levels of syndecan-1 (239 ± 113 to 184 ± 106 ng/mL, p = 0.005); blood glucose levels also decreased significantly (162 ± 112 to 146 ± 74 mg/dL, p = 0.02). Administration of probiotics to patients with advanced CKD was associated with decreases in syndecan-1 and blood glucose levels, indicating potential improvements in metabolism and decreased systemic inflammation.

Monitoring Renal Function in HIV Patients Without Kidney Disease Using Endothelial Biomarkers: A Prospective Pilot Study.

This study aimed to investigate the association between novel biomarkers and renal injury in people with HIV (PWH). A cohort study was carried out with PWH under chronic use of antiretroviral therapy (ART), followed at a public outpatient service. Clinical and laboratory parameters of the patients were evaluated year by year, from 2015 [at baseline (year 1, Y1)] to 2019 [year 5 (Y5)]. At baseline, biomarkers of renal damage (e.g., neutrophil gelatinase-associated lipocalin-NGAL, monocyte chemoattractant protein-1-MCP-1, and kidney injury molecule-1-KIM-1) and endothelial activation or glycocalyx damage [e.g., intercellular adhesion molecule 1 (ICAM-1), E-selectin, and syndecan-1] were quantified using enzyme-linked immunosorbent assays and their levels were used to classify patients into different groups. However, only syndecan-1 showed a significant correlation with serum creatinine (p < .001) and glomerular filtration rate (GFR) (p = .003) over the years. Moreover, both serum creatinine and GFR in almost 5 years were significantly associated with serum levels of syndecan-1 at baseline. The multivariate linear regression with confounders showed a significant and independent association between GFR and levels of syndecan-1 and CD4 cell count in the beginning of the study, as well as age in Y5. The data reinforce the screening for kidney diseases with novel biomarkers, especially syndecan-1, as an important strategy for a timely diagnostic and therapeutic approach.

Blood component resuscitative strategies to mitigate endotheliopathy in a murine hemorrhagic shock model.

Resuscitation with plasma components has been shown to improve endotheliopathy induced by hemorrhagic shock, but the optimal resuscitation strategy to preserve the endothelial glycocalyx has yet to be defined. The aim of this study was to determine if resuscitation with lactated Ringer's (LR), whole blood (WB), packed red blood cells (RBCs), platelet-rich plasma (PRP), platelet poor plasma, balanced RBC:PRP (1:1), or day 14 (d14) RBC would best minimize endothelial damage following shock. Male C57BL/6 mice were hemorrhaged to a goal mean arterial pressure of 25 mm Hg for 1 hour. Unshocked sham mice served as controls. Mice were then resuscitated with equal volumes of LR, WB, RBC, PRP, platelet poor plasma, 1:1, or d14 RBC and then sacrificed at 1, 4, or 24 hours (n = 5). Serum was analyzed for syndecan-1, ubiquitin C-terminal hydrolase L1, and cytokine concentrations. Lungs underwent syndecan-1 immunostaining, and lung injury scores were calculated after hematoxylin and eosin. Proteolytic cleavage of the endothelial glycocalyx was assessed by serum matrix metalloprotease 9 levels. Serum syndecan-1 and ubiquitin C-terminal hydrolase L1 levels were significantly increased following resuscitation with d14 RBC compared with other groups. Early elevation in lung syndecan-1 staining was noted in LR-treated mice, while d14 mice showed decreased staining compared with sham mice following shock. Lung injury scores were significantly elevated 4 hours after resuscitation with LR and d14 RBC compared with WB. Serum matrix metalloprotease 9 levels were significantly increased at 1 and 4 hours in d14 mice compared with sham mice. Systemic inflammation was increased in animals receiving LR, 1:1, or d14 RBC. Resuscitation with WB following hemorrhagic shock reduces endothelial syndecan-1 shedding and mitigates lung injury. Aged RBC and LR fail to attenuate endothelial injury following hemorrhagic shock. Further research will be necessary to determine the effect of each of these resuscitative fluids in a hemorrhagic shock model with the addition of tissue injury.

Endothelial glycocalyx shedding during active COVID-19 infection and its effect on disease severity

ABSTRACT Background COVID-19 pandemic was caused by the SARS-CoV-2 virus that was thought to be associated with microvascular endothelial injury. This study aimed to demonstrate the effect of COVID-19 on markers of endothelial shedding and its effect on patient morbidity and mortality. Settings and design This was a prospective cohort study. Methods This study was conducted at the isolation hospital at Alexandria Main University hospitals on 40 adult patients infected with COVID-19. Patients were divided according to the severity of the presenting symptoms into two groups; moderate and severe. Serum levels of Syndecan-1 and Heparan sulfate were measured at hospital admission and at the end of the first week. Clinical and demographic data along with laboratory investigations and outcomes were compared between the two groups. Results Our results indicated that patients with severe symptoms of COVID-19 had notably high levels of syndecan-1 and Heparan sulfate compared to patients with moderate symptoms on day 1 and day 7. Further investigations revealed that D-dimer, CRP, and IL-6 levels in patients with severe symptoms were higher in patients with severe symptoms. Our results also indicated that IL-6 increased on day 4 and gradually decreased on day 7 in both groups. Furthermore, serum levels of Syndecan-1, Heparan sulfate, D-dimer, and CRP decreased gradually from day 1 to day 7 in both groups. There was an association between markers of endothelial shedding with thrombotic and cardiovascular complications. It seems that the serum Syndecan-1 and Heparan sulfate might be good candidates to monitor COVID-19 activity. Conclusion Patients with severe symptoms of COVID-19 have high serum levels of syndecan 1 compared to patients with moderate symptoms and have higher mortality and more prolonged hospital stay due to more endothelial injury and inflammatory reaction. Syndecan-1 may be used to monitor disease progression and severity.

Exploring the pathophysiological mechanism of interstitial edema focusing on the role of macrophages and their interaction with the glycocalyx

ObjectivesGlycocalyx lines the vascular intraluminal space that regulates fluid movement between the intra- and extra-vascular compartments. The depletion of glycocalyx (GCX) is associated with leukocyte accumulation, possibly causing the endothelial cells to become hyperpermeable in various organs, including oral tissues. Whether neutrophils or macrophages are responsible for developing interstitial edema remains controversial. We explored the pathophysiological mechanism of interstitial edema by examining the role of reactive neutrophils and macrophages and their interactions with GCX. MethodsAn anti-MHC class I antibody was administered intravenously to male BALB/c mice to induce pulmonary edema. Pulmonary edema was evaluated by measuring the lung wet-to-dry weight ratio. Changes in the GCX were evaluated by electron microscopy and measurements of the serum level of soluble syndecan-1. Heparin sulfate was administered to examine its protective effect on the GCX. The macrophages were depleted using clodronate to examine their role in developing edema. ResultsThe GCX degradation induced by the anti-MHC class I antibody was accompanied by increased serum syndecan-1 and heparan sulfate levels. Macrophage depletion inhibited the development of pulmonary edema, and the administration of supplemental heparin suppressed the edema. ConclusionsWe demonstrated that the degradation of the GCX induced by the anti-MHC class I antibody was suppressed by macrophage depletion. These results suggest that macrophages may play a key role in interstitial edema. Heparin inhibited both the degradation of the GCX and interstitial edema. This study’s results may be extrapolated to develop an interventional strategy for inhibiting interstitial edema in various organs.