Soluble Urokinase Plasminogen Activator Receptor Levels Correlation with Other Inflammatory Factors in Prognosis of Disability and Death in Patients with Ischemic Stroke

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker elevated in cardiovascular diseases. The aim of this 3-year follow-up prospective study was to evaluate suPAR levels in patients with a first ischemic stroke in correlation with CRP, PCT, NT-proCNP and endothelin 1-21 and to investigate the impact of suPAR on the outcome. Fifty-one patients (mean age 73.7+ = 11.9 years, 26 female and 25 male) were included. Samples were collected on the first (suPAR 1), third (suPAR 3) and seventh days after stroke onset (suPAR 7). Plasma samples were analyzed using ELISA. A phone interview was conducted to collect follow-up information after 24 and 36 months (modified Rankin Scale, mRS). A positive correlation between suPAR levels and other inflammatory biomarkers (except endothelin 3) was observed. A positive correlation between suPAR 3 and mRS score at 24 months was observed (p = 0.042). The logistic regression model revealed no significant effect of suPAR on death occurrence in the first 24 months: suPAR 1 (p = 0.8794), suPAR 3 (p = 0.2757), and suPAR 7 (p = 0.3652). The suPAR level is a potential inflammatory marker in ischemic stroke, and there is a correlation with other markers. There is no major impact on mortality. However, the suPAR level is associated with a degree of disability or dependence in daily activities 2 years after a stroke.

The Soluble Urokinase-Type Plasminogen Activator Receptor as a Biomarker for Survival and Early Treatment Effect in Metastatic Colorectal Cancer

The soluble urokinase-type plasminogen activator receptor (suPAR) is prognostic for overall survival (OS) in colorectal cancer (CRC). Our study explored the association between baseline suPAR and OS and progression-free survival (PFS) in metastatic CRC (mCRC). It is also the first study to explore the association between the initial change in suPAR level and OS, PFS and the first CT response evaluation. The study included 132 patients with mCRC treated with chemotherapy (FOLFIRI) with or without an EGFR-inhibitor. Blood samples were drawn before the first treatment cycle and in between the first and second treatment cycle. suPAR levels were determined using an ELISA assay. Using the Kaplan-Meyer method, we demonstrated a significantly shorter OS for patients with suPAR levels above the median (HR = 1.79, 95%CI = 1.10–2.92, p = 0.01). We also showed association between plasma suPAR level, gender and performance status (PS). However, we could not show any association with PFS, and analysis on the change in suPAR level provided no significant results. The results showing association between baseline suPAR and OS are in line with previous findings.

Association of preoperative plasma suPAR levels with intraoperative sublingual microvascular perfusion in patients undergoing major non-cardiac surgery

Introduction: The plasma suPAR level has previously been associated with postoperative complications and has been shown to be an independent predictor of coronary microvascular function and flow reserve. We investigated the association between preoperative suPAR levels and intraoperative sublingual microvascular perfusion in patients undergoing elective major non-cardiac surgery. Methods: This study included 100 patients undergoing major non-cardiac surgery between February 2019 and September 2020. The primary objective was to investigate the association between preoperative suPAR and intraoperative sublingual De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and Consensus PPV (small). Secondary objectives were to investigate the associations between these sublingual microcirculatory variables and (1) complications and (2) mean arterial pressure. EDTA blood was collected before induction of anesthesia and plasma suPAR levels were determined using the suPARnostic quick triage lateral flow assay. Sublingual microcirculation was monitored with Sidestream DarkField (SDF+) imaging technique at 20 minutes after induction of anesthesia before surgical incision (baseline) and then every 30 minutes until emergence from anesthesia. Results: A decrease of 0.7 mm-1 in the De Backer score, 2.5% in the Consensus PPV, and 2.8% in the Consensus PPV (small) from baseline measurement was observed for every 1 ng/ml increase of suPAR or 1 additional minute of intraoperative time. De Baker score did not change significantly from baseline (p=0.404), while Consensus PPV and Consensus PPV (small) decreased significantly from baseline (p<0.001 in both cases). The De Backer score, the Consensus PPV, and the Consensus PPV (small) correlated with postoperative complications. Mean arterial pressure correlated with De Backer score (p=0.487) but not with Consensus PPV (p=0.506) or Consensus PPV (small) (p=0.697) during the intraoperative period. Conclusion: Preoperative suPAR levels and prolonged operative duration were associated with intraoperative impairment of sublingual microvascular perfusion in patients undergoing elective major non-cardiac surgery.

Soluble urokinase plasminogen activator receptor and its complicated role in hemodialysis (HD) patients with Covid-19 infection

Background: Soluble urokinase plasminogen receptor (suPAR) is a protein in the blood that has been described to reflect the severity status of systemic inflammation. Aims and Objective: We investigated the association between admission suPAR levels and severity and outcome of HD patients with Covid-19 infection. Materials and Methods: In an observational study of adult HD patients hospitalized for Covid-19, we measured suPAR levels in plasma samples. The time table for those measurements were as follows: at the beginning of admission, after hemoperfusion (HP) session for those patients that received them, and just before discharge. Results: Of the 17 patients (7 were male), 13 patients received HP (mean age: 74 years old). The median suPAR level was 12.94 ng/ml. For those who undertook HP in HD unit median suPAR level was before session 12.95 ng/mil and 6.2 ng/ml at the end of each session (p<0.05). 3 patients had suPAR level below 7 ng/ml. 2 of them survived without developing pleural effusions. 7 patients discharged from the hospital with median suPAR level 12.08 ng/ml which did not differ significantly from the median suPAR level of the diceased ones (13.68 ng/ml). Conclusion: Admission of suPAR levels in HD patients hospitalized for Covid-19 do not seem to be predictive for their clinical course in general. Chronic Kidney Disease and its relation to suPAR independently of patients’ inflammation status may be the key component for our notice. Despite that, in patients where low levels of suPAR combined with absence of pleural effusions the prognosis was excellent.

Plasma gradient of soluble urokinase-type plasminogen activator receptor is linked to pathogenic plasma proteome and immune transcriptome and stratifies outcomes in severe COVID-19

Disease caused by SARS-CoV-2 coronavirus (COVID-19) has resulted in significant morbidity and mortality world-wide. A systemic hyper-inflammation characterizes the severe COVID-19 disease often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. In the present study we report higher plasma abundance of soluble urokinase-type plasminogen activator receptor (sUPAR), expressed by an abnormally expanded circulating myeloid cell population, in severe COVID-19 patients with ARDS. Plasma sUPAR level was found to be linked to a characteristic proteomic signature of plasma, linked to coagulation disorders and complement activation. Receiver operator characteristics curve analysis identified a cut-off value of sUPAR at 1996.809 pg/ml that could predict survival in our cohort (Odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower sUPAR level than this threshold concentration was associated with a differential expression of the immune transcriptome as well as favourable clinical outcomes, both in terms of survival benefit (Hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus we identified sUPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.

The Unique Difference Between Serum Level of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Steroid-Resistant Nephrotic Syndrome Children Treated with an Alkylating Agent and Calcineurin Inhibitors

Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading contributor to chronic kidney disease (CKD), and calcineurin inhibitors (CNIs) or monoclonal antibodies are currently the best identified therapy. Meanwhile, some developing countries still use alkylating agents (AA) such as cyclophosphamide (CPA) to treat SRNS due to economic reasons. Objectives: This study aims to determine the employability of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker for monitoring therapy in SRNS children and compare the clinical improvement with those treated with an AA and CNIs. Methods: This was a retrospective cohort study conducted at Hasan Sadikin Hospital, Indonesia. The data was collected from July 2019 to July 2020 from 70 children with FSGS. Clinical signs were evaluated monthly, and serum suPAR level was measured at the third and sixth months following therapy. Two-way repeated measures ANOVA was carried out to compare the differences in suPAR level at baseline with the third and sixth months in SRNS patients who received AA and CNIs. Results: The mean age was nearly similar between the two groups based on the t-test (P = 0.140). Steroid-resistant nephrotic syndrome was more frequent in boys than in girls (P = 0.020), according to the Chi-square test. Baseline serum suPAR level was not significantly different between the two groups. In the third month, the daily urinary protein level was higher in SRNS patients that received the AA compared to the CNIs group (P < 0.001). There was a significant interaction between time and treatment (F(2,138) = 7.203, P = 0.001), with higher suPAR level in SRNS patients that received the AA compared to those administered with CNIs at the 3rd and 6th months, but this difference was not statistically significant (P > 0.05). Conclusions: As a noninvasive tool, suPAR is a promising modality in monitoring SRNS therapy, and CNIs have a tendency to achieve faster remission than the AA.

MO866SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR AND COVID-19 INFECTION IN HEMODIALYSIS PATIENTS

Background and Aims Soluble urokinase plasminogen receptor (suPAR) is a protein in the blood that has been described to reflect the severity status of systemic inflammation. At the same time an elevated level of suPAR has been independently associated with incident chronic kidney disease. We investigated the association between admission suPAR levels and severity and outcome of Hemodialysis (HD) patients with Covid-19 infection. Method In an observational study of adult HD patients hospitalized for Covid-19, we measured suPAR levels in plasma samples. The time table for those measurements were as follows: at the beginning of admission, after hemoperfusion (HP) session for those patients that received them, and just before discharge. Results Of the 17 patients (7 were male), 13 patients received HP (mean age: 74 years old). The median suPAR level was 12.94 ng/ml. For those who undertook HP median suPAR level was 10.55 ng/ml at the end of each session (p=NS). 3 patients had suPAR level below 7 ng/ml. 2 of them survived without developing pleural effusions. 7 patients discharged from the hospital with median suPAR level 12.94 ng/ml which did not differ significantly from the median suPAR level of the diceased ones (13.68 ng/ml). Conclusion Admission of suPAR levels in HD patients hospitalized for Covid-19 do not seem to be predictive for their clinical course in general. Chronic Kidney Disease backround and its relation to suPAR levels independently of patients’ inflammation status may be the key component for our notice. Despite that, in patients where low levels of suPAR combined with absence of pleural effusions the prognosis was excellent.

MO948CHANGES OF SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR (SUPAR) AFTER CADAVERIC KIDNEY TRANSPLANTATION AND ASSOCIATION WITH KIDNEY FUNCTION

Background and Aims The soluble urokinase plasminogen activator receptor (suPAR), a marker of podocyte injury, has been implicated in pathogenesis of various kidney diseases, especially in focal segmental glomerulosclerosis. It correlates to the activation level of immune system. SuPAR predicted all course mortality in hemodialysis patients, but was not tested as a prognostic biomarker in kidney transplant patients. The aim of this study was to evaluate changes of suPAR concentration after kidney transplantation and to test its relation to graft function. Method We examined patients, who underwent cadaveric kidney transplantation (Tx) from 2019/05/23 to 2020/07/30 in the Hospital of Lithuanian University of Health Sciences. We evaluated level of suPAR biomarker before Tx, 12 days after Tx and 3 months after Tx. We used the suPARnostic Quick Triage test by ViroGates (Medtech, Denmark) for testing suPAR concentration. The suPARnostic Quick Triage test is based on the lateral flow principle. The device consists of a nitrocellulose membrane with two immobilized antibody zones and a running buffer with gold particles. The quantitative results are read by the aLF Reader with a detection interval of 2-15 ng/mL suPAR. Data on serum creatinine level and eGFR were collected at the same time points. Creatinine was tested using Analyzer AU680, Beckman Coulter, USA (Kinetic Jaffe traceable to the IDMS reference method). The statistical data analysis was performed using SPSS 23.0 software. Results 35 patients were included into the study, 57% of men and 43% of woman. Mean age of patients - 47±13.5 years. Mean suPAR level before transplantation was 8.7±4.2 ng/ml. It was a trend towards lower mean suPAR level 12 days after Tx (5.9±2.8 ng/ml, p=0.1) as compared to before Tx. It was significant decrease of suPAR level 3 months after Tx (3.9±1.1 ng/ml, p=0.003) as compared to before Tx. There was no suPAR relation to patient’s age. Serum creatinine and eGFR did not correlate with suPAR levels measured at the same time (before Tx, 12 days, and 3 months after Tx). We did not find relation between suPAR level before transplantation and creatinine level and eGFR 12 days after Tx. We found a significant negative correlation between suPAR level before transplantation and creatinine level 3 months after transplantation (r = -0.4, p = 0.049), but not eGFR 3 months after Tx. In a group of patients with eGFR ≥45 ml/min/1.73m2 3 months after transplantation mean suPAR level before Tx (9.5±4.3 ng/ml), after 12 days (5.8±2.6 ng/ml), and 3 months after Tx (3.8±0.87 ng/ml) was not different than in group of patients with eGFR &lt; 45 ml/min/1.73m2 (8±4.1 ng/ml, 5.2±3.5 ng/ml, 3.9±1.5 ng/ml accordingly), p&gt;0.05. Conclusion There was a significant gradual decrease of suPAR levels during 3 months after transplantation. No correlation of suPAR levels and transplanted kidney function was confirmed. A larger study is needed to assess whether suPAR could predict long term outcomes in kidney transplantation.

Soluble urokinase-type plasminogen activator receptor strongly predicts global mortality in acute heart failure patients: insight from the STADE-HF registry

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.