Soluble Urokinase Plasminogen Activator Receptor Research Articles

Assessment of clinical utility and predictive potential of pre-chemotherapy soluble urokinase plasminogen activator receptor: Observational single center study.

Alteration of urokinase plasminogen activator receptor (uPAR) in neoplasms is a prerequisite for invasiveness and metastatic ability. In the present study, we aimed to evaluate the relationship of pre-chemotherapy soluble uPAR (suPAR) with the odds for metastasis, lack of disease control, and its predictive ability for progression-free survival (PFS). Baseline plasma suPAR levels were measured by ELISA in 89 patients with various cancers prior to initiation of systemic treatment. Patients were followed prospectively until metastatic progression or death. TCGA Pan-Cancer dataset was mined for available RNAseq expression data of the PLAUR gene in patients with breast, colon, and lung cancer, and therelevant genomic and clinical data were extracted for further analysis. Pre-chemotherapy suPAR levels were significantly associated with white blood cell counts and fibrinogen and were significantly elevated both in patients with metastatic disease and in patients with progression. Increasing suPAR was significantly associated with odds for progression in the prespecified multivariate analysis (odds ratio 2.47, 95% confidence interval 1.3 - 5.11). In univariate Cox regression, suPAR was predictive of shortened progression-free survival (PFS) (hazard ratio 1.065, 95% confidence interval 1.002 - 1.13; p = 0.041). There was a trend towards shortened PFS in patients with higher baseline suPAR levels (cutoff 8.1 ng/mL). In the TCGA lung cancer cohort, PLAUR mRNA expression was significantly associated with shortened PFS in both univariate and multivariate analyses. High PLAUR gene expression conferred significant survival disadvantage only in patients with colon and lung cancer. SuPAR may bear predictive potential for adverse outcomes in cancer, but its utility as a biomarker seems to be more pronounced in cancers with associated inflammatory state.

Growth differentiation factor-15 as a biomarker of atherosclerotic coronary plaque: Value in people living with and without HIV.

BackgroundIncreased rates of cardiovascular diseases (CVD) and larger subclinical high-risk coronary plaques in coronary CT angiography have been observed in people living with HIV (PLWH) treated with antiretroviral therapy (ART) compared to HIV-uninfected people. Growth differentiation factor-15 (GDF-15) is a cytokine emerging as an optimal marker for CVD in the general population.MethodsWe cross-sectionally analyzed plasma of 95 PLWH on ART and 52 controls. We measured GDF-15, fibroblast growth factor-21 (FGF-21), glucagon-like peptide-2 (GLP-2), soluble urokinase plasminogen activator receptor (suPAR), CRP, and anti-CMV and anti-EBV IgG levels. All participants had no clinical CVD and underwent coronary CT angiography with the 3D reconstruction of coronary artery atherosclerotic plaques. Total plaque volume (TPV) and low attenuation plaque volume (LAPV, defined as density <30 Hounsfield Units) were calculated (mm3).ResultsIn both PLWH and controls, GDF-15 levels were increased in participants with presence of coronary plaque vs. without (p = 0.04 and p < 0.001, respectively) and correlated with TPV (r = 0.27, p = 0.009 and r = 0.62, p < 0.001, respectively) and LAPV (r = 0.28, p = 0.008, r = 0.60, p < 0.001, respectively). However, in a multivariate model, GDF-15 was independently associated with LAPV in controls only (adjusted OR 35.1, p = 0.04) and not in PLWH, mainly due to confounding by smoking. Other markers were not independently associated with plaque volume, except for anti-EBV IgGs in controls (adjusted OR 3.51, p = 0.02).ConclusionIn PLWH, GDF-15 and smoking seemed to synergistically contribute to coronary plaque volume. Conversely, increased GDF-15 levels were associated with the presence of coronary artery plaques in people without HIV, independently of CV risk factors.

Soluble urokinase Plasminogen Activator Receptor (suPAR) levels are predictive of COVID-19 severity: an Italian experience

BackgroundThe soluble urokinase Plasminogen Activator Receptor (suPAR) has been identified as a reliable marker of COVID-19 severity, helping in personalizing COVID-19 therapy. This study aims to evaluate the correlation between suPAR levels and COVID-19 severity, in relation to the traditional inflammatory markers. MethodsSera from 71 COVID-19 patients were tested for suPAR levels using Chorus suPAR assay (Diesse Diagnostica Senese SpA, Italy). suPAR levels were compared with other inflammatory markers: IL-1β, IL-6, TNF-α, circulating calprotectin, neutrophil and lymphocyte counts, and Neutrophil/Lymphocytes Ratio (NLR). Respiratory failure, expressed as P/F ratio, and mortality rate were used as indicators of disease severity. ResultsA positive correlation of suPAR levels with IL-6 (r = 0.479, p = 0.000), TNF-α (r = 0.348, p = 0.003), circulating calprotectin (r = 0.369, p = 0.002), neutrophil counts (r = 0.447, p = 0.001), NLR (r = 0.492, p = 0.001) has been shown. Stratifying COVID-19 population by suPAR concentration above and below 6 ng/mL, we observed higher levels of circulating calprotectin (10.1 μg/mL, SD 7.9 versus 6.4 μg/mL, SD 7.5, p < 0.001), higher levels of P/F ratio (207.5 IQR 188.3 vs 312.0 IQR 127.8, p = 0.013) and higher mortality rate. Median levels of suPAR were increased in all COVID-19 patients requiring additional respiratory support (Nasal Cannula, Venturi Mask, BPAP and CPAP) (6.5 IQR = 4.9) compared to the group at room air (4.6 IQR = 4.2). ConclusionsuPAR levels correlate with disease severity and survival rate of COVID-19 patients, representing a promising prognostic biomarker for the risk assessment of the disease.

Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID-19.

Background Venous thromboembolism (VTE) contributes significantly to COVID-19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID-19. Whether suPAR levels identify patients with COVID-19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID-19 with suPAR and D-dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine-Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D-dimer levels. There was a positive association between suPAR and D-dimer (β=7.34; P=0.002). Adjusted for clinical covariables, including D-dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51-4.75]; P<0.001). Findings were consistent when stratified by D-dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D-dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D-dimer in patients hospitalized for COVID-19. Combining suPAR and D-dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

The role of soluble urokinase plasminogen activator receptor (suPAR) in patients with cancer: a review of the current literature.

Aim Several biomarkers are currently used as diagnostic and prognostic tools in patients with cancer. Soluble urokinase plasminogen activator receptor (suPAR) is elevated in acute and chronic inflammatory procedures and several observational studies during the last 20 years have investigated its role in oncology. The purpose of this article was to review the current literature regarding suPAR's role in clinical practice. Methods A systematic literature search of PubMed, Scopus, OpenGrey and Cochrane Library databases through September 2021 was conducted using the following search terms: "supar"or "soluble urokinase plasminogen receptor" and "cancer" or "malignancy". Original articles reporting on suPAR's role in the diagnosis, prognosis and prediction of therapeutic outcomes in patients with confirmed or suspected cancer were included. Results Among 45 found articles, the most were observational cohort studies. The included studies were further categorized by cancer site. SuPAR level was higher in patients with cancer compared to healthy controls, but its diagnostic and prognostic accuracy differs depending on the site of cancer. Conclusion SuPAR has promising aspects in the field of oncology and public health and future research should further investigate its use in clinical practice. As it is elevated in different types of cancer, it could potentially serve as an adjunctive tool for the mass screening of patients with non-specific signs of cancer, but larger cohort studies that support these findings must be conducted.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) in the Emergency Department (Ed): A Tool for the Assessment of Elderly Patients.

Emergency department (ED) overcrowding is a global issue setting challenges to all care providers. Elderly patients are frequent visitors of the ED and their risk stratification is demanding due to insufficient assessment methods. A prospective cohort study was conducted to determine the risk-predicting value of a prognostic biomarker, soluble urokinase plasminogen activator receptor (suPAR), in the ED, concentrating on elderly patients. SuPAR levels were determined as part of standard blood sampling of 1858 ED patients. The outcomes were assessed in the group of <75 years (=younger) and ≥75 years (=elderly). The elderly had higher median suPAR levels than the younger (5.4 ng/mL vs. 3.7 ng/mL, p < 0.001). Increasing suPAR levels were associated with higher probability for 30-day mortality and hospital admission in all age groups. SuPAR also predicted 30-day mortality when adjusted to other clinical factors. SuPAR acts successfully as a nonspecific risk predictor for 30-day mortality, independently and with other risk-assessment tools. Low suPAR levels predict positive outcomes and could be used in the discharging process. A cut-off value of 4 ng/mL could be used for all ED patients, 5 ng/mL being a potential alternative in elderly patients.

Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.

ContextNovel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome.ObjectiveAssess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways.Design/ParticipantsProof-of-concept study where individuals with type 2 diabetes (n = 40) and increased albumin-to-creatinine ratio (ACR) were randomly assigned to receive a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months with 3-month follow-up.Main Outcomes MeasuresChange in ACR was assessed by analysis of covariance adjusted for age, sex, weight loss, and baseline value. Prespecified subgroup analysis for patients with micro- vs macroalbuminuria at baseline was performed. Change in homeostatic model assessment for insulin resistance (HOMA-IR), circulating markers of dicarbonyl detoxification (methylglyoxal-derived hydroimidazolone 1, glyoxalase-1, and hydroxyacetone), DNA-damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor) were assessed as exploratory endpoints.ResultsFMD was well tolerated with 71% to 95% of the participants reporting no adverse effects. After 6 months, change in ACR was comparable between study groups [110.3 (99.2, 121.5) mg/g; P = 0.45]. FMD led to a reduction of ACR in patients with microalbuminuria levels at baseline [−30.3 (−35.7, −24.9) mg/g; P ≤ 0.05] but not in those with macroalbuminuria [434.0 (404.7, 463.4) mg/g; P = 0.23]. FMD reduced HOMA-IR [−3.8 (−5.6, −2.0); P ≤ 0.05] and soluble urokinase plasminogen activator receptor [−156.6 (−172.9, −140.4) pg/mL; P ≤ 0.05], while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in acylcarnitines was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction [−1.9 (−3.7, −0.1), P ≤ 0.05]) was sustained.ConclusionsImprovement of microalbuminuria and of markers of insulin resistance, lipid oxidation, and senescence suggest the potential beneficial effects of periodic fasting in type 2 diabetes.

458-P: Inflammatory Markers and Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Objective: We aimed to assess the role of chronic inflammation in the pathogenesis of cardiovascular autonomic neuropathy (CAN) , a serious complication of type 1 diabetes (T1D) . Methods: We leveraged an ongoing randomized, placebo-controlled clinical trial targeting inflammation with salsalate in individuals with T1D, to measure a panel of 40 inflammatory markers (Figure) in baseline samples. Measures of CAN included standardized cardiovascular autonomic reflex tests (CARTs) (E/I, Valsalva, 30/15 ratios) and indices of heart rate variability (HRV) . We used Spearman-rank to assess the correlations between inflammatory markers and CAN measures, and linear regression to adjust for age and hemoglobin A1c. Results: The Figure displays the correlation between biomarkers and CAN measures in 58 T1D participants (mean age 51 ± 13 years, and HbA1c 8.4 ± 1.8%) . Amongst all biomarkers, we noted a singular negative correlation between soluble urokinase plasminogen activator receptor (suPAR) and measures of CAN, which remained significant in multivariable analysis (E/I ratio p=0.005, Valsalva p=0.037, RFA p=0.019, LFA p=0.023) . Conclusion: Amongst a large panel of inflammatory markers, we found suPAR to have a notable association with CAN. SuPAR is an immune-mediated signaling glycoprotein which levels are strong predictors of risk in patients with diabetes, thus its role in CAN warrants further exploration. Disclosure L.Ang: None. L.Zhao: None. E.L.Feldman: None. S.Hayek: n/a. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. S.V.G.Gunaratnam: None. Y.Huang: None. K.R.Mizokami-stout: None. C.Martin: Advisory Panel; Nevro Corp. J.Reiss: n/a. A.Burant: None. A.Vasbinder: None. C.Launius: None. Funding NIH/NIDDK-1-R01-DK-107956-01

Value of soluble urokinase plasminogen activator receptor as biomarker of sepsis in critically ill children in intensive care unit

Value of soluble urokinase plasminogen activator receptor as biomarker of sepsis in critically ill children in intensive care unit

Comparison of the Mortality Prediction Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in COVID-19 and Sepsis.

In the last years, biomarkers of infection, such as the soluble urokinase plasminogen activator receptor (suPAR), have been extensively studied as potential diagnostic and prognostic biomarkers in the intensive care unit (ICU). In this study, we investigated whether this biomarker can be used in COVID-19 and non-COVID-19 septic patients for mortality prediction. Serum suPAR levels were measured in 79 non-COVID-19 critically ill patients upon sepsis (within 6 h), and on admission in 95 COVID-19 patients (66 critical and 29 moderate/severe). The non-COVID-19 septic patients were matched for age, sex, and disease severity, while the site of infection was the respiratory system. On admission, COVID-19 patients presented with higher suPAR levels, compared to non-COVID-19 septic patients (p < 0.01). More importantly, suPAR measured upon sepsis could not differentiate survivors from non-survivors (p > 0.05), as opposed to suPAR measured on admission in COVID-19 survivors and non-survivors (p < 0.0001). By the generated ROC curve, the prognostic value of suPAR in COVID-19 was 0.81, at a cut-off value of 6.3 ng/mL (p < 0.0001). suPAR measured early (within 24 h) after hospital admission seems like a specific and sensitive mortality risk predictor in COVID-19 patients. On the contrary, suPAR measured at sepsis diagnosis in non-COVID-19 critically ill patients, does not seem to be a prognostic factor of mortality.

Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated with Severity of Fibrosis in Patients with Primary Sclerosing Cholangitis.

The soluble urokinase-type plasminogen activator receptor (suPAR) has evolved as a useful biomarker for different entities of chronic liver disease. However, its role in patients with primary sclerosing cholangitis (PSC) is obscure. We analyzed plasma levels of suPAR in 84 patients with PSC and compared them to 68 patients with inflammatory bowel disease (IBD) without PSC and to 40 healthy controls. Results are correlated with clinical records. suPAR concentrations were elevated in patients with PSC compared to patients with IBD only and to healthy controls (p < 0.001). Elevated suPAR levels were associated with the presence of liver cirrhosis (p < 0.001) and signs of portal hypertension (p < 0.001). suPAR revealed a high accuracy for the discrimination of the presence of liver cirrhosis comparable to previously validated noninvasive fibrosis markers (area under the curve (AUC) 0.802 (95%CI: 0.702–0.902)). Further, we demonstrated that suPAR levels may indicate the presence of acute cholangitis episodes (p < 0.001). Finally, despite the high proportion of PSC patients with IBD, presence of IBD and its disease activity did not influence circulating suPAR levels. suPAR represents a previously unrecognized biomarker for diagnosis and liver cirrhosis detection in patients with PSC. However, it does not appear to be confounded by intestinal inflammation in the context of IBD.

Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor.

Background: Elevated soluble urokinase plasminogen activator receptor (suPAR) is highly associated with increased risk of diabetic complications. Dapagliflozin is a drug inhibiting the sodium-glucose co-transporter 2 in the kidney to decrease blood glucose, while also decreasing risk of kidney disease, heart failure, and death. Therefore, we have investigated suPAR as a monitor for treatment effect with dapagliflozin in diabetes. Methods: suPAR was measured in two double-blinded randomized clinical cross-over trials. The first trial investigated the effect of a single dose dapagliflozin 50 mg or placebo 12 h after intake, in individuals with type 1 diabetes and albuminuria. The second trial investigated the effect of a daily dose dapagliflozin 10 mg or placebo for 12 weeks, in individuals with type 2 diabetes and albuminuria. suPAR was measured in serum samples taken, in the acute trial, after treatment with dapagliflozin and placebo, and in the long-term trial, before and after treatment with dapagliflozin and placebo. Effect of dapagliflozin on suPAR levels were assessed using paired t-test. Results: 15 participants completed the acute trial and 35 completed the long-term trial. Mean difference in suPAR between dapagliflozin and placebo in the acute trial after 12 h was 0.70 ng/ml (95% CI: 0.66; 1.33, p = 0.49). In the long-term trial the mean difference was 0.06 ng/ml (95% CI -0.15; 0.27, p = 0.57). Conclusion: Based on our findings we conclude that suPAR is not a feasible marker to monitor the effect of treatment with dapagliflozin. Thus, a further search of suitable markers must continue.

Soluble Urokinase Receptor Levels Are Not Affected by the Systemic Inflammatory Response to Anesthesia and Operative Trauma

Introduction: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker of the level of chronic systemic inflammation and the general condition of the patient. We aimed to investigate the impact of general anesthesia and major surgery on perioperative suPAR and C-reactive protein (CRP) levels. Methods: This study included patients undergoing elective major noncardiac surgery with an expected duration of ≥2 h under general anesthesia. Inclusion criteria were age ≥18 years and American Society of Anesthesiologists’ physical status I–IV. Blood was drawn 30 min prior to induction of anesthesia (preoperatively), as well as 30 min after emergence from anesthesia (postoperatively). Plasma suPAR levels were determined using the suPARnostic® Quick Triage lateral flow assay. CRP measurements were performed by particle-enhanced immunoturbidimetric assay. Results: The difference in preoperative and postoperative suPAR levels was not statistically significant (7.7 [5.28–10.4] ng/mL vs. 7.15 [5.68–9.8] ng/mL, p = 0.462). CRP levels increased significantly during surgery (0.81 [0.24–2.1] mg/dL vs. 5.76 [2.2–8.75] mg/dL, p < 0.001). No correlation was observed between CRP and suPAR levels, both preoperatively (rho = 0.127; p = 0.208) and postoperatively (rho = 0.017; p = 0.87). A statistically significant increase was also observed in postoperative white blood cell count (7.576 vs. 10.711, p < 0.001). Conclusion: General anesthesia and operative trauma did not affect perioperative suPAR levels despite the activation of systemic inflammatory response.

Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways

Introduction: Concomitant risk factors challenge the mechanistic understanding of cardiac aging. We determined the degree to which the left atrial function could be distinguished by advanced cardiac magnetic resonance (CMR) imaging in older adults and assessed associations between the left atrial function and the plasma biomarkers related to biological aging and cardiovascular disease [serum monocyte chemoattractant protein-1 (MCP1), matrix metallopeptidase 9 (MMP-9), B-type natriuretic peptides (BNPs), galectin-3 (Gal-3), high-sensitivity cardiac troponin I (hsTn1), high-sensitivity C-reactive protein (hs-CRP), and soluble urokinase plasminogen activator receptor (sUPAR)]. Methods: Among a cross-sectional population-based cohort of older adults, longitudinal LA strain including reservoir strain (εs), conduit strain (εe), and booster strain (εa) as well as peak strain rates (SRs, SRe, SRa) were determined using CMR and studied in association with blood biomarkers. Results: We studied 243 community adults (42.8% female, mean age 70.3 ± 9.5 years). In bivariate analysis, εe and SRe were reduced in gradation with increasing risk factors (all p values <0.0001). Corresponding levels of sUPAR (ng/mL) were quantitatively higher in older adults with <2 risk factors (2.5 ± 1.6 vs. 1.7 ± 1.3, p = 0.0005), in those with ≥2 risk factors (3.3 ± 2.4 vs. 1.7 ± 1.3, p < 0.0001), compared to young adults; including between older adults with ≥2 risk factors and older adults with <2 risk factors (3.3 ± 2.4 vs. 2.5 ± 1.6, p = 0.017). Based on multivariate analysis, sUPAR was significantly associated with both εe (OR 1.52, p = 0.006) and SRe decline (OR 1.5, p = 0.019). The associations between Gal-3 and εe reduction (OR 1.2, p = 0.022) and between BNP and SRe decline were generally weaker (OR 1.03, p = 0.027). The addition of sUPAR to a model consisting of age, risk factors, Gal-3, and BNPs increased the area under the curve of εe from 0.72 to 0.77 (p = 0.015). Conclusion: By advanced CMR imaging, a panel of circulating biomarkers comprising galectin, MMP-9 and sUPAR were associated with left atrial dysfunction in older adults. Higher levels of Gal-3 and MMP-9 may be suggestive of fibrotic mechanisms in left atrial aging while impairments in left atrial strain seen in association with circulating sUPAR may be related to immune activation in the left atrium in response to left atrial remodeling and fibrotic processes.

Clinical and Immunological Predictors of Hemorrhagic Fever with Renal Syndrome Outcome during the Early Phase.

The ability to accurately predict the early progression of hemorrhagic fever with renal syndrome (HFRS) is crucial for reducing morbidity and mortality rates in severely affected patients. However, the utility of biomarkers for predicting clinical outcomes remains elusive in HFRS. The aims of the current study were to analyze the serum levels of immune function-related proteins and identify novel biomarkers that may help ascertain clinical outcomes of HFRS. Enzyme-linked immunosorbent assay, Luminex, and bioanalyzer assays were used to quantitatively detect 15 biomarkers in 49 serum samples of 26 patients with HFRS. High hemoglobin (HGB) and low urine output (UO) levels were identified as potential biomarkers associated with the acute HFRS. The serum soluble urokinase plasminogen activator receptor (suPAR) and C-X-C motif chemokine ligand 10 (CXCL10) values increased in the early phase of diseases. Elevated suPAR, interleukin-10 (IL-10), CXCL10, and decreased transforming growth factor-beta 3 (TGF-β3) were representative predictors of the disease severity. Upregulation of the HGB showed a significant correlation with high levels of suPAR and CXCL10. Reduced UO positively correlated with increased suPAR, CXCL10, and TGF-β2, and decreased vascular endothelial growth factor and TGF-β3. The changing HGB and UO criteria, high suPAR, IL-10, CXCL10, and low TGF-β3 of HFRS raise significant awareness for physicians regarding prospective biomarkers for monitoring early warning signs of HFRS. This study provides critical insights into the clinical and immunological biomarkers for disease severity and progression in patients with HFRS to identify early predictions of fatal outcomes.

Personalised Approach to Diagnosing and Managing Ischemic Stroke with a Plasma-Soluble Urokinase-Type Plasminogen Activator Receptor.

Background: The increasing incidence of ischemic stroke has led to the search for a novel biomarker to predict the course of disease and the risk of mortality. Recently, the role of the soluble urokinase plasminogen activator receptor (suPAR) as a biomarker and indicator of immune system activation has been widely examined. Therefore, the aim of the current study was to assess the dynamics of changes in serum levels of suPAR in ischemic stroke and to evaluate the prognostic value of suPAR in determining mortality risk. Methods: Eighty patients from the Department of Neurology, diagnosed with ischemic stroke, were enrolled in the study. Residual blood was obtained from all the patients on the first, third and seventh days after their ischemic stroke and the concentrations of suPAR and C-reactive protein (CRP), as well as the number of leukocytes and National Institute of Health’s Stroke Scale (NIHSS) scores, were evaluated. Results: On the first day of ischemic stroke, the average suPAR concentration was 6.55 ng/mL; on the third day, it was 8.29 ng/mL; on the seventh day, it was 9.16 ng/mL. The average CRP concentration on the first day of ischemic stroke was 4.96 mg/L; on the third day, it was 11.76 mg/L; on the seventh day, it was 17.17 mg/L. The number of leukocytes on the first day of ischemic stroke was 7.32 × 103/mm3; on the third day, it was 9.27 × 103/mm3; on the seventh day, it was 10.41 × 103/mm3. Neurological condition, which was assessed via the NIHSS, on the first day of ischemic stroke, was scored at 10.71 points; on the third day, it was scored at 12.34 points; on the seventh day, it was scored at 13.75 points. An increase in the values of all the evaluated parameters on the first, third and seventh days of hospitalisation was observed. The patients with hypertension, ischemic heart disease and type 2 diabetes showed higher suPAR and CRP concentrations at the baseline as well as on subsequent days of hospitalisation. The greatest sensitivity and specificity were characterised by suPAR-3, where a value above 10.5 ng/mL resulted in a significant increase in mortality risk. Moreover, an NIHSS-1 score above 12 points and a CRP-3 concentration above 15.6 mg/L significantly increased the risk of death in the course of the disease. Conclusions: The plasma suPAR concentration after ischemic stroke is strongly related to the patient’s clinical status, with a higher concentration on the first and third days of stroke resulting in a poorer prognosis at a later stage of treatment. Therefore, assessing the concentration of this parameter has important prognostic value.

The Role of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in the Context of Aneurysmal Subarachnoid Hemorrhage (aSAH)-A Prospective Observational Study.

ObjectiveOutcome after aneurysmal subarachnoid hemorrhage (aSAH) is highly variable and largely determined by early brain injury and delayed cerebral ischemia (DCI). Soluble urokinase plasminogen activator receptor (suPAR) represents a promising inflammatory marker which has previously been associated with outcome in traumatic brain injury and stroke patients. However, its relevance in the context of inflammatory changes after aSAH is unclear. Here, we aimed to characterize the role of circulating suPAR in both serum and cerebrospinal fluid (CSF) as a novel biomarker for aSAH patients.MethodsA total of 36 aSAH patients, 10 control patients with unruptured abdominal aneurysm and 32 healthy volunteers were included for analysis. suPAR was analyzed on the day of admission in all patients. In aSAH patients, suPAR was also determined on the day of DCI and the respective time frame in asymptomatic patients. One- and two-sample t-tests were used for simple difference comparisons within and between groups. Regression analysis was used to assess the influence of suPAR levels on outcome in terms of modified Rankin score.ResultsSignificantly elevated suPAR serum levels (suPAR-SL) on admission were found for aSAH patients compared to healthy controls, but not compared to vascular control patients. Disease severity as documented according to Hunt and Hess grade and modified Fisher grade was associated with higher suPAR CSF levels (suPAR-CSFL). In aSAH patients, suPAR-SL increased daily by 4%, while suPAR-CSFL showed a significantly faster daily increase by an average of 22.5% per day. Each increase of the suPAR-SL by 1 ng/ml more than tripled the odds of developing DCI (OR = 3.06). While admission suPAR-CSFL was not predictive of DCI, we observed a significant correlation with modified Rankin's degree of disability at discharge.ConclusionElevated suPAR serum level on admission as a biomarker for early inflammation after aSAH is associated with an increased risk of DCI. Elevated suPAR-CSFL levels correlate with a higher degree of disability at discharge. These distinct relations and the observation of a continuous increase over time affirm the role of inflammation in aSAH and require further study.

Discrimination and Inflammation in Adolescents of Color

BackgroundThis study examined how experiences with discrimination relate to inflammation, a key biological pathway in mental and physical illnesses, and whether associations are moderated by gender across two samples of adolescents of color. MethodsStudy 1 was a longitudinal study of 419 African American adolescents assessed on discrimination (ages 19–20), with trajectories of biomarkers of low-grade inflammation (C-reactive protein and soluble urokinase plasminogen activator receptor) measured from ages 25 to 29. Study 2 was a cross-sectional study of 201 eighth graders of color assessed on discrimination and mechanistic indicators of a proinflammatory phenotype: 1) in vitro studies of immune cells’ inflammatory cytokine responses to stimuli; 2) in vitro studies of cells’ sensitivity to anti-inflammatory agents; 3) circulating numbers of classical monocytes, key cellular drivers of low-grade inflammation; and 4) a composite of six biomarkers of low-grade inflammation. ResultsInteractions of discrimination by gender were found across both studies. In study 1, African American males experiencing high discrimination showed increasing trajectories of soluble urokinase plasminogen activator receptor over time (p < .001). In study 2, adolescent boys of color experiencing greater discrimination evinced a more proinflammatory phenotype: larger cytokine responses to stimuli (p = .003), lower sensitivity to anti-inflammatory agents (p = .003), higher numbers of classical monocytes (p = .008), and more low-grade inflammation (p = .003). No such associations were found in females. ConclusionsDiscrimination is a pressing societal issue that will need to be addressed in efforts to promote health equity. This study suggests that adolescent males of color may be particularly vulnerable to its effects on mental health–relevant inflammatory processes.

Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure

SummaryMost patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Soluble urokinase plasminogen activator receptor and decline in kidney function among patients without kidney disease

ABSTRACTBackgroundHospitalized patients are at an increased risk of developing kidney disease after discharge, often despite the absence of any clinical indicators during hospitalization. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation that can be measured from routine blood samples. We determined whether elevated suPAR during hospitalization is associated with a decline in estimated glomerular filtration rate (eGFR) after discharge.MethodsThis was a retrospective longitudinal cohort study of patients without detectable kidney disease presenting to the emergency department on two separate occasions during a 3-year period. The association between suPAR and a decline in eGFR was assessed by linear mixed models for repeated measures adjusting for age, sex, C-reactive protein, sodium, diabetes, hypertension and cardiovascular disease.ResultsIn total, 5124 patients (median age 65.9 years, 51.0% female) were included. The median suPAR was 2.9 ng/mL, the median time to readmission was 144 days and the expected rate of eGFR decline over this period was 5.1 mL/min/1.73 m2/year. Adjusting for other risk factors, patients with suPAR <3, 3–6 or ≥6 ng/mL had an expected eGFR decline of 4.3, 5.2 or 9.0 mL/min/1.73 m2/year, respectively. Similarly, patients with suPAR in the lowest (<2.4 ng/mL), middle (2.4–3.6 ng/mL) or highest (≥3.6 ng/mL) tertile had an expected eGFR decline of 4.2, 4.6 or 6.5 mL/min/1.73 m2/year, respectively. In both cases, a higher suPAR level was significantly and independently associated with a higher rate of eGFR decline (P < .001).ConclusionsA higher suPAR level was associated with accelerated eGFR decline among patients presenting to the emergency department, suggesting that routine suPAR measurements may have utility for the early detection of kidney disease.