Soluble urokinase-type plasminogen activator receptor strongly predicts global mortality in acute heart failure patients: insight from the STADE-HF registry.
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ABSTRACT: Background
Whether soluble urokinase-type plasminogen activator receptor (suPAR) could be a valuable prognostic indicator remains uncertain.Materials & methods
Patients from STADE-HF (Soluble Suppression of Tumorigenesis-2 as a Help for Management of Diagnosis, Evaluation and Management of Heart Failure) were included for analysis.Results
95 patients were included. The suPAR level of expression was significantly higher in the group of patients who died at one month (7.90 ± 4.35 ng/ml vs 11.94 ± 6.86 ng/ml; p < 0.05) or 1 year (7.28 ± 4.27 ng/ml vs 11.81 ± 4.88 ng/ml; p < 0.01), but there was no significant difference according to the readmission.Conclusion
High suPAR levels during hospitalization for acute heart failure were highly predictive for the risk of mortality, but not the risk of readmission.
SUBMITTER: Huet F
PROVIDER: S-EPMC8147742 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC9683642 | biostudies-literature
Project description:Background and objectivesBlack Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria.Design, setting, participants, & measurementsUsing data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death.ResultsAt baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02).ConclusionsHigher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.
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Project description:The soluble urokinase-type plasminogen activator receptor (suPAR) and the urokinase-type plasminogen activator receptor (uPAR) have been proposed as useful biomarkers of tumor progression. Recently, suPAR was associated with chemoresistance in lung cancer. However, its clinical significance in leukemia has not previously been investigated. The present study examined the plasma levels of suPAR and the expression of the uPAR on bone marrow (BM) cells in 86 patients with leukemia at diagnosis prior to chemotherapy and 26 normal subjects (control group). The plasma suPAR levels were measured using ELISA, whilst uPAR expression was assayed by flow cytometry analysis. In addition, cell surface uPAR expression on K562 and multidrug-resistant K562/ADM cell lines was studied by western blotting. On admission and follow-up, the levels of suPAR in patients with leukemia were significantly increased compared with controls. Systemic levels of suPAR were strongly associated with the numbers of white blood cells. A case was defined as uPAR-positive (uPAR+) if >20% of the gated cells expressed uPAR. In comparison with 26 healthy BM samples that were negative for uPAR expression, 48 (55.8%) of the 86 leukemia patients were uPAR+. uPAR expression on the cell surface of multidrug-resistant K562/ADM cells was increased compared with that on K562 cells. In conclusion, plasma suPAR expression may be a useful marker for subtype classification of patients with leukemia and cell surface uPAR may be associated with resistance to chemotherapy or disease progression.
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Project description:Data from clinical studies, cell culture, and animal models implicate the urokinase (uPA)/Plasminogen (Plg) system in the development of atherosclerosis and aneurysms. However, the mechanisms through which uPA/Plg stimulate these diseases are not yet defined. We used genetically modified, atherosclerosis-prone mice, including mice with macrophage-specific uPA overexpression to clarify mechanisms of uPA/Plg-accelerated atherosclerosis and aneurysm formation. Microarray studies were performed to identify potential mediators of uPA-accelerated atherosclerosis. These studies identified S100A8 and S100A9 mRNA as the most highly upregulated transcripts in uPA-overexpressing macrophages; upregulation of S100A9 protein in uPA-overexpressing macrophages was confirmed by Western blotting. S100A8/A9, which are atherogenic in mice and are expressed in human atherosclerotic plaques, are also upregulated in aortae of mice with uPA-overexpressing macrophages, and macrophage S100A9 mRNA is upregulated by exposure of wild-type macrophages to medium from uPA-overexpressing macrophages. Bioinformatics analysis of the microarray data suggest significant effects of uPA overexpression on cell migration and cell-matrix interactions. Our results confirm—in a second animal model—that macrophage-expressed uPA stimulates atherosclerosis and aortic dilation. They also implicate specific pathways in uPA/Plg-accelerated atherosclerosis and aneurysmal disease.
2011-05-03 | GSE29028 | GEO