scholarly journals Soluble Urokinase Receptor (SuPAR) in COVID-19–Related AKI

2020 ◽  
Vol 31 (11) ◽  
pp. 2725-2735 ◽  
Author(s):  
Tariq U. Azam ◽  
Husam R. Shadid ◽  
Pennelope Blakely ◽  
Patrick O’Hayer ◽  
Hanna Berlin ◽  
...  

BackgroundAKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19–related AKI is unknown.MethodsIn a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI.ResultsOf the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups.ConclusionsAdmission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.

2021 ◽  
Vol 12 (7) ◽  
pp. 1-4
Author(s):  
Ioannis Griveas ◽  
Antonios Schoinas ◽  
Anthi Balitsari ◽  
Gerasimos Asimakopoulos ◽  
Evaggelos Pratilas

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.


2001 ◽  
Vol 69 (8) ◽  
pp. 5182-5185 ◽  
Author(s):  
Nicole P. Juffermans ◽  
Pascale E. P. Dekkers ◽  
Annelies Verbon ◽  
Peter Speelman ◽  
Sander J. H. van Deventer ◽  
...  

ABSTRACT Patients with tuberculosis had higher expression of monocyte urokinase receptor (uPAR) and CD11b than controls. In vitro, lipoarabinomannan and lipopolysaccharide (LPS) from Escherichia coli shared the ability to enhance uPAR and CD11b expression on monocytes and granulocytes. In healthy volunteers, LPS induced increases in monocyte and granulocyte uPAR and CD11b.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ioannis Griveas ◽  
Antonis Schinas ◽  
Anthoula Balitsari ◽  
Gerasimos Asimakopoulos ◽  
Evangelos Pratilas

Abstract 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.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Ahmedz WIdiasta ◽  
Kurnia Wahyudi ◽  
Husna Nugrahapraja ◽  
Yunia Sribudiani ◽  
Dedi Rachmadi

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ruta Skaiste Macionyte ◽  
Marius Bardauskas ◽  
Ruta Vaiciuniene ◽  
Inga Arune Bumblyte

Abstract 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.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 183-183
Author(s):  
Solvej Lippert ◽  
Kasper Drimer Berg ◽  
Peter Iversen ◽  
Gunilla Høyer-Hansen ◽  
Ib Jarle Christensen ◽  
...  

183 Background: New biomarkers are warranted to distinguish between indolent and aggressive prostate cancer (PCa). The urokinase plasminogen activator receptor (uPAR) plays an important role in pericellular proteolysis by binding urokinase plasminogen activator (uPA). This is required for degradation of the extracellular matrix and for cancer invasion. In addition to binding uPAR, uPA cleaves uPAR liberating uPAR(I) and uPAR(II-III). Intact, uPAR(I-III), and uPAR(II-III) can be liberated from the cell surface resulting in three different uPAR forms in circulation. The different uPAR forms are strong prognostic markers in several cancers. We measured the uPAR forms in plasma from patients with different stages of PCa. Methods: Between February 1, 2012 and October 1, 2014, 400 patients with PCa (se table) had plasma samples obtained. The levels of intact uPAR [uPAR(I-III)], intact uPAR + cleaved uPAR domains II+III [uPAR(I-III) + uPAR(II-III)], and cleaved uPAR domain I [uPAR(I)] were determined in citrated plasma samples with two-site sandwich time-resolved fluorescence immunoassays (TR-FIAs). Results: Plasma uPAR(I-III) + uPAR(II-III) and uPAR(I) were significantly higher in hormone naïve patients and CRPC patients compared to patients with localized disease (see table). Quantification of intact uPAR(I-III) revealed no significant differences between the three groups. Conclusions: Our findings suggest that uPAR(I-III) + uPAR(II-III) and uPAR(I) are associated with higher tumor stage as well as advanced PCa disease. These associations suggest that uPAR domains in plasma harbour prognostic value for PCa patients. Further studies are warranted to validate the use of uPAR forms as biomarkers for PCa. [Table: see text]


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Zuxiong Huang ◽  
Ning Wang ◽  
Shuiwen Huang ◽  
Yi Chen ◽  
Shida Yang ◽  
...  

Aims. Soluble urokinase plasminogen activator receptor (suPAR) reflects the immune activation in circumstances of inflammation and infection. It has been considered as a risk biomarker associated with poor outcome in various low-grade inflammation and infectious diseases. The study is aimed at investigating whether suPAR has a predictive value with short-term survival in patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Methods. Serum suPAR expression was compared among patients with different states of chronic hepatitis B virus infection. Sixty HB-ACLF patients were recruited as the training cohort and followed up for 90 days. Serum suPAR level and the clinical relevance with short-term outcome were investigated. The temporal dynamics of suPAR were evaluated in 50 HB-ACLF patients with available serum sequentially at baseline, week 2 and week 4. Another 167 HB-ACLF patients were enrolled to validate the predictive value of suPAR with respect to the prognosis. Results. Serum suPAR level was significantly increased in HB-ACLF patients compared to non-ACLF patients. In the training set of HB-ACLF, we observed higher suPAR level, INR, MELD score, and more complications in nonsurvivors than survivors. Longitudinal analysis revealed an increased trend of suPAR level in nonsurvivors during week 0 to week 4 and the modest decline in survivors. It showed that the synchronous suPAR level was higher in nonsurvivors at all indicated time points. Elevated suPAR level at baseline was identified as a strong predictor of a 90-day mortality of HB-ACLF patients. It was confirmed suPAR>16.26 ng/ml had a positive predictive value of 72.22% and a negative predictive value of 77.88% for poor outcome in the validation cohort. Conclusions. Serum suPAR level increases significantly in HB-ACLF patients and associated with a 90-day mortality. It suggests that suPAR might be a potential biomarker to predict the prognosis of HB-ACLF patients.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rafal N. Wlazel ◽  
Katarzyna Szwabe ◽  
Agnieszka Guligowska ◽  
Tomasz Kostka

Abstract Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker whose clinical value has been tested in various groups of patients. The aim of the present study was to determine the suPAR level in a previously uninvestigated population of 182, generally healthy, community-dwelling seniors aged 74–89 years. In addition to suPAR level, selected laboratory parameters of heart and kidney function, lipid and C-reactive protein levels were determined. A group of 45 younger individuals aged 24–66 years was used for comparison. The seniors had higher suPAR levels than younger controls: 3.79 ng/mL (95% CI 3.64–3.96 ng/mL) vs. 3.16 ng/mL (95% CI 2.86–3.45 ng/mL). These levels increased further with advancing age, and were similar in women and men. A multiple regression model confirmed that biomarker level was related to cardiac function, renal function and inflammation, and this remained after adjusting for age. These correlation patterns were similar in older women and men.


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