The significance of serum urokinase plasminogen activation receptor (suPAR) in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies

Kaya, Selçuk; Köksal, İftihar; Menteşe, Ahmet; Sönmez, Mehmet; Sümer, Ayşegül; Yıldırım, Seval Sönmez; Yılmaz, Gürdal

doi:10.1016/j.ijid.2013.04.004

Cited by 11 publications

(5 citation statements)

References 16 publications

(9 reference statements)

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“…Furthermore, mean plasma suPAR levels in patients were significantly different from mean suPAR levels found in healthy controls (2.7 ng/ml) from time point ER onwards ( Figure 1A). The concentrations we found in samples from healthy controls were similar to those found in healthy controls in previous studies [17][18][19].…”

Section: Plasma Supar Concentrations After Traumasupporting

confidence: 90%

Soluble urokinase-type plasminogen activator levels are related to plasma cytokine levels but have low predictive value for mortality in trauma patients

Timmermans

Vaneker

Scheffer

et al. 2015

Journal of Critical Care

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Section: Plasma Supar Concentrations After Traumasupporting

confidence: 90%

Soluble urokinase-type plasminogen activator levels are related to plasma cytokine levels but have low predictive value for mortality in trauma patients

Timmermans

Vaneker

Scheffer

et al. 2015

Journal of Critical Care

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“…Although neutrophils appeared to represent the major source of suPAR in ICU patients in vivo, suPAR might be released from other cells, including non-circulating cells, as well. This would, for instance, explain why suPAR serum levels can be elevated in neutropenic patients with infections [42]. In fact, the cellular origin of suPAR may substantially differ in organ-specific disease settings, and such mechanisms may additionally contribute to circulating suPAR in ICU patients with organ failure(s).…”

Section: Discussionmentioning

confidence: 99%

Neutrophils are a main source of circulating suPAR predicting outcome in critical illness

et al. 2019

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Background: Circulating levels of soluble urokinase plasminogen activation receptor (suPAR) have been proposed as a prognostic biomarker in patients with critical illness and sepsis. However, the origin of suPAR in sepsis has remained obscure. We investigated the potential cellular sources of suPAR by analyzing membrane-bound urokinase plasminogen activator receptor (uPAR, CD87) and evaluated its clinical relevance in critically ill patients. Methods: We studied 87 critically ill patients (44 with sepsis, 43 without sepsis) from the medical intensive care unit (ICU) in comparison to 48 standard care patients with infections and 27 healthy controls in a prospective single-center noninterventional cohort study. Cellular uPAR expression of different immune cell subsets (by flow cytometry from peripheral blood) and corresponding serum suPAR concentrations were determined upon ICU admission and at day 3. Furthermore, we analyzed the effects of serum from sepsis patients on the activation and uPAR cleavage of primary human neutrophils and macrophages in vitro. Results: In healthy controls, uPAR (CD87) expression was detected on nearly all blood neutrophils and monocytes, but only scarcely on lymphocytes. While uPAR expression on monocytes was maintained in ICU patients, only 58% of neutrophils from critically ill patients expressed uPAR, which was significantly lower than in healthy controls or standard care patients. Concomitantly, serum suPAR levels were significantly increased in ICU patients. We noted a clear inverse correlation between low neutrophilic uPAR and high serum suPAR in standard care and ICU patients, indicating that shedding of uPAR from activated neutrophils represents a main source of suPAR in systemic inflammation. Both low uPAR and high suPAR were closely associated with mortality in critically ill patients. Furthermore, serum from sepsis patients induced uPAR protein expression and subsequent receptor shedding on isolated primary neutrophils, but not on macrophages, in vitro. Conclusions: The inverse correlation between low uPAR surface expression on neutrophils and high serum suPAR in critically ill patients supports that neutrophils are a main source of shed suPAR proteins in systemic inflammation. Furthermore, high suPAR levels and low neutrophilic uPAR expression predict mortality in ICU patients.

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“…Among the 17 eligible studies, 9 studies including 1237 patients reported the usefulness of suPAR for diagnosing infections131415161718192021, and 10 studies including 3041 patients reported its usefulness for predicting mortality14212223242526272829. The characteristics of the studies are presented in Table S1.…”

Section: Resultsmentioning

confidence: 99%

Serum soluble urokinase-type plasminogen activator receptor as a biological marker of bacterial infection in adults: a systematic review and meta-analysis

Han

Zhao

et al. 2016

Sci Rep

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The serum concentration of soluble urokinase-type plasminogen activator receptor (suPAR) reflects immune activation. We performed a meta-analysis to evaluate the usefulness of suPAR for the diagnosis and prognosis of bacterial infections. PubMed, Embase and Cochrane Library databases were searched for studies reporting the detection of suPAR in adult patients with bacterial infections. Seventeen studies were selected from 671 studies. The pooled sensitivity and specificity of suPAR for diagnosing infection were 0.73 and 0.79, respectively, and the area under the summary receiver operating characteristic curve (AUC) was 0.82. Subgroup analyses revealed suPAR showed similar AUC values for diagnosing sepsis and bacteremia, but the AUC for differentiating sepsis from systemic inflammatory response syndrome (SIRS) was only 0.68. Elevated suPAR levels were significantly associated with a high risk of death, with a pooled risk ratio of 3.37 (95% confidence interval, 2.60–4.38). The pooled sensitivity and specificity for predicting mortality were 0.70 and 0.72, respectivfely, with an AUC of 0.77. Serum suPAR could be a biomarker for the diagnosis and prognosis of bacterial infection, but it is relatively ineffective for differentiating sepsis from SIRS. Further investigation is required to evaluate whether using of suPAR in combination with other biomarkers can improve diagnostic efficacy.

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The significance of serum urokinase plasminogen activation receptor (suPAR) in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies

Cited by 11 publications

References 16 publications

Soluble urokinase-type plasminogen activator levels are related to plasma cytokine levels but have low predictive value for mortality in trauma patients

Soluble urokinase-type plasminogen activator levels are related to plasma cytokine levels but have low predictive value for mortality in trauma patients

Neutrophils are a main source of circulating suPAR predicting outcome in critical illness

Serum soluble urokinase-type plasminogen activator receptor as a biological marker of bacterial infection in adults: a systematic review and meta-analysis

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