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

Azam, Tariq U.; Shadid, Husam; Blakely, Pennelope; O’Hayer, Patrick; Berlin, Hanna; Pan, Michael; Zhao, Peiyao; Zhao, Lili; Pennathur, Subramaniam; Pop‐Busui, Rodica; Altintas, Izzet; Tingleff, Jens; Stauning, Marius Ahm; Andersen, Ove; Adami, Maria‐Evangelia; Solomonidi, Nicky; Tsilika, Maria; Tober‐Lau, Pinkus; Αrnaoutoglou, Eleni; Keitel, Verena; Tacke, Frank; Chalkias, Athanasios; Loosen, Sven H.; Giamarellos‐Bourboulis, Evangelos J.; Eugen‐Olsen, Jesper; Reiser, Jochen; Hayek, Salim S.

doi:10.1681/asn.2020060829

Cited by 118 publications

(123 citation statements)

References 69 publications

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“…Soluble urokinase plasminogen activator receptor (suPAR) seems to be such a screening tool. We and others, recently demonstrated that suPAR concentrations above 6 μ g/l herald worsening to SRF 14 days earlier 4,5 . The positive predictive value for the early prediction of SRF was as high as 85.9%.…”

Section: Introductionmentioning

confidence: 67%

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Anakinra To Prevent Respiratory Failure In COVID-19

Kyriazopoulou¹,

Panagopoulos

Metallidis

et al. 2020

Preprint

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Introduction The management of pneumonia caused by SARS-CoV-2 should rely on early recognition of the risk for progression to severe respiratory failure (SRF) and its prevention. We investigated if early suPAR (soluble urokinase plasminogen activator receptor)-guided anakinra treatment could prevent COVID-19-assocated SRF. Methods In this open-label prospective trial, 130 patients admitted with SARS-CoV-2 pneumonia SARS-CoV-2 and suPAR levels ≥6 μg/l were assigned to subcutaneous anakinra 100mg once daily for 10 days. The primary outcome was the incidence of SRF at day 14. Secondary outcomes were 30-day mortality, changes in sequential organ failure assessment (SOFA) score, of cytokine-stimulation pattern and of circulating inflammatory mediators. Equal number of propensity score-matched comparators for comorbidities, severity on admission and standard-of care (SOC) were studied. Results The incidence of SRF was 22.3% (95% CI, 16.0-30.2%) among anakinra-treated patients and 59.2% (95% CI, 50.6-67.3%; P: 4.6 x 10-8) among SOC comparators (hazard ratio, 0.30; 95%CI, 0.20-0.46). 30-day mortality was 11.5% (95% CI, 7.1-18.2%) and 22.3% (95% CI, 16.0-30.2%) respectively (hazard ratio 0.49; 95% CI 0.25-0.97%; P: 0.041). Anakinra treatment was associated with decrease in SOFA score and in circulating interleukin (IL)-6, sCD163 and sIL2-R; the serum IL-10/IL-6 ratio on day 7 was inversely associated with the change in SOFA score. Duration of stay at the intensive care unit and at hospital was shortened compared to the SOC group; the cost of hospitalization was decreased. Conclusions Early suPAR-guided anakinra treatment is associated with decrease of the risk for SRF and restoration of the pro- /anti-inflammatory balance.

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Section: Introductionmentioning

confidence: 67%

“…An important point of the SAVE study is the strategy to select for early anakinra treatment using the predictive biomarker suPAR. In previous studies in COVID-19 and in sepsis, this marker turned out to be able to predict the likelihood for unfavourable outcome 4,5,8,9 .…”

Section: Discussionmentioning

confidence: 95%

Anakinra To Prevent Respiratory Failure In COVID-19

Kyriazopoulou¹,

Panagopoulos

Metallidis

et al. 2020

Preprint

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“…None of the patients with suPAR < 4.60 ng/ml required dialysis. The highest suPAR tertial was strongly associated with incident AKI (aOR: 9.15; 95%CI: 3.64−22.93) 158 . In view of these results, suPAR might be used as a potential biomarker for AKI and COVID‐19 severity.…”

Section: Complicationsmentioning

confidence: 88%

Risk factors for severe and critically ill COVID‐19 patients: A review

Gao

Ding

Dong

et al. 2020

Allergy

1,166

864

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The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.

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“…A pilot clinical study has also shown high levels of soluble urokinase-type plasminogen activator receptor (suPAR) in COVID-19 patients [76]. COVID-19 patients with high suPAR levels are at higher risk of developing severe respiratory failure [76] and acute kidney injury [77], which confirms the importance of fibrinolysis in the severity of the disease. There is therefore a need for research focusing on the role of fibrinolysis and its components in the pathogenesis of 10…”

Section: Accepted Manuscriptmentioning

confidence: 91%

Hemostasis in Coronavirus Disease 2019—Lesson from Viscoelastic Methods: A Systematic Review

2021

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Haemostatic unbalance is often observed in patients with coronavirus disease 2019 (COVID-19), and patients with severe disease are at high risk of developing thromboembolic complications. Viscoelastic methods (VEMs), including thrombelastography (TEG) and thromboelastometry (TEM), provide data on the nature of haemostatic disturbance. In this systematic review, we assessed the performance of TEG and TEM in the assessment of blood coagulation and fibrinolysis in patients with COVID-19. PubMed, Scopus, Web of Science Core Collection, medRxiv and bioRxiv were systematically searched for clinical studies evaluating TEG and/or TEM variables in COVID-19 individuals. Ten studies, with a total of 389 COVID-19 patients, were included, and VEMs were performed in 292 of these patients. Most patients (90%) presented severe COVID-19 and required mechanical ventilation. TEG and TEM variables showed that these patients displayed hypercoagulability and fibrinolysis shutdown, despite the use of appropriate thromboprophylaxis. However, the mechanism underlying these phenomena and their clinical significance in COVID-19 patients who developed thrombosis, is still not clear. Further studies are warranted if VEMs might help to identify those at highest risk of thrombotic events and who therefore may derive the greatest benefit from antithrombotic therapy.

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

Cited by 118 publications

References 69 publications

Anakinra To Prevent Respiratory Failure In COVID-19

Anakinra To Prevent Respiratory Failure In COVID-19

Risk factors for severe and critically ill COVID‐19 patients: A review

Hemostasis in Coronavirus Disease 2019—Lesson from Viscoelastic Methods: A Systematic Review

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