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Dooley MA, Manzi S, Ramsey-Goldman R, Nived O, Steinsson K, Zoma AA, Ruiz-Irastorza G, Lim SS, Kalunian KC, Inanc M, van
Vollenhoven RF, Ramos-Casals M, Kamen DL, Jacobsen S, Peschken CA, Askanase A, Stoll T, Bruce IN, Wetterö J, Sjöwall C. Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus. J Autoimmun. 2020 Jan;106:102340. doi: 10.1016/j.jaut.2019.102340. Epub 2019 Oct 17. PMID 31629628.
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Rovina, Nikoletta; Akinosoglou, Karolina; Eugen-Olsen, Jesper; Hayek, Salim; Reiser, Jochen; Giamarellos-Bourboulis, Evangelos J. (2020-04-30). "Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia". Critical
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Enocsson H, Idoff C, Gustafsson A, Govender M, Hopkins F, Larsson M, Nilsdotter-Augustinsson Å, Sjöwall J. Soluble
Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19. Front Med (Lausanne). 2021 Dec 2;8:791716. doi:
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Enocsson H, Wirestam L, Dahle C, Padyukov L, Jönsen A, Urowitz MB, Gladman DD, Romero-Diaz J, Bae SC, Fortin PR, Sanchez-Guerrero J, Clarke AE, Bernatsky S, Gordon C, Hanly JG, Wallace DJ, Isenberg DA, Rahman A, Merrill JT, Ginzler E, Alarcón GS, Chatham WW, Petri M, Khamashta M, Aranow C, Mackay M,
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In the general population, the suPAR level is higher in females than in males. The median suPAR level for men and women in blood donors is 2.22 ng/mL and 2.54 ng/mL, respectively. In general, women have slightly higher suPAR than men. suPAR levels are higher in serum than in plasma for the
170:
In the kidneys, suPAR plays a role in regulating the permeability of the glomerular filtration barrier. An elevated suPAR level is associated with chronic renal diseases, the future incidence of chronic renal diseases, and declining eGFR. A high level is significantly associated with mortality and
153:
In COVID-19, an early elevation of suPAR, e.g. in patients that present with symptoms of SARS-CoV-2 infection, is associated with an increased risk of severe COVID-19 development, which may lead to respiratory failure, acute kidney injury, and death. Clinical relevant cut-offs have been identified
144:
In the emergency departments, suPAR can aid in the triage and risk assessment of patients. This allows for many patients can be discharged rather than admitted. This also ensures that the most ill patients are prioritised first and put under careful observation without delay. A suPAR level below
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The suPAR level can be measured using the suPARnostic® product line. suPARnostic® is a CE-IVD certified antibody-based product range applied for quantitative measurements of suPAR in the clinical setting. Three product formats are available: 1) TurbiLatex, validated for clinical chemistry
429:
Oulhaj A et al. Admission levels of
Soluble Urokinase Plasminogen Activator Receptor (suPAR) are Associated with the Development of Severe Complications in Hospitalised COVID-19 Patients: A Prospective Cohort Study. Int J Infect Dis. 2021 Apr 20;107:188-194. doi: 10.1016/j.ijid.2021.04.026.
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The molecular weight of suPAR varies between 24–66 kDa due to variations in posttranslational glycosylations. Additional isoforms generated by alternative splicing have been described on the RNA level, but whether these are transcribed and their possible roles remain unclear.
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uPAR has cleavage sites for several proteases in the linker region (chymotrypsin, elastase, matrix metalloproteases, cathepsin G, plasmin, urokinase plasminogen activator (uPA, or urokinase), and in the GPI anchor (phospholipase C and D, cathepsin G, plasmin).
232:
systems currently including the Roche
Diagnostics cobas c501/2 and c701/2 systems; the Siemens ADVIA XPT and Atellica systems, and the Abbott Architect c and Alinity systems. 2) Quick Triage, which is a platform that is applied at the Point-Of-Care. 3) ELISA.
295:
Sjöwall, C; Martinsson, K; Cardell, K; Ekstedt, M; Kechagias, S (2014). "Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in non-alcoholic fatty liver disease". Translational
Research. 165 (6):
51:. Therefore, suPAR is a marker of disease severity and aggressiveness and is associated with morbidity and mortality in several acute and chronic diseases. suPAR levels have been observed to increase with age. suPAR is present in
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M. Huang, A. P. Mazar, G. Parry, A. A.-R. "Higazi, A. Kuo and D. B. Cines. Crystallisation of soluble urokinase receptor (suPAR) in complex with urokinase amino-terminal fragment (1-143)". Acta
Crystallographica (2005): D61 (6),
46:
and
Vitronectin. The soluble version of uPAR, called suPAR, results from the cleavage and membrane-bound uPAR during inflammation or immune activation. The suPAR concentration is positively correlated to the activation level of
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Chew-Harris J, Appleby S, Richards AM, Troughton RW, Pemberton CJ. Analytical, biochemical and clearance considerations of soluble urokinase plasminogen activator receptor (suPAR) in healthy individuals. Clin
Biochem (2019)
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Botha S, Fourie CM, Schutte R, Eugen-Olsen J, Pretorius R, Schutte AE. Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population. Int J Cardiol.
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Rovina N, Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Crit Care. 2020 Apr 30;24(1):187. doi: 10.1186/s13054-020-02897-4.
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Stephens RW, Pedersen AN, Nielsen HJ, Hamers MJAG, Høyer-Hansen G, Rønne E, Dybkjær E, Danø K, Brünner N. ELISA determination of soluble urokinase receptor in blood from healthy donors and cancer patients. Clin Chem (1997)
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Enocsson, Helena; Wetterö, Jonas; Skogh, Thomas; Sjöwall, Christopher (2013). "Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus". Translational
Research. 162 (5):
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binding. When uPA is bound to the receptor, a cleavage between the GPI-anchor and D3 forms suPAR. Of the three suPAR forms: suPAR1-3, suPAR2-3, and suPAR1, suPAR2-3 is the chemotactic agent for promoting the immune system.
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Eugen-Olsen J, Andersen O, Linneberg A, et al. Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J Intern Med.
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Musetti C, Quaglia M, Cena T et al. Circulating suPAR levels are affected by glomerular filtration rate and proteinuria in primary and secondary glomerulonephritis. J Nephrol 2015 Jun;28(3):299-305.
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Eugen-Olsen, J. et al. "Circulating
Soluble Urokinase Plasminogen Activator Receptor Predicts Cancer, Cardiovascular Disease, Diabetes and Mortality in the General Population."Journal of Internal Medicine
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Eugen-Olsen, J. et al. "Circulating Soluble Urokinase Plasminogen Activator Receptor Predicts Cancer, Cardiovascular Disease, Diabetes and Mortality in the General Population."Journal of Internal Medicine
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4 ng/mL indicates a good prognosis in acute medical patients and supports discharge. In contrast, patients presenting with a suPAR level above 6 ng/mL have a high risk of a negative outcome.
529:
Wei C, Li J, Adair BD, Zhu K, Cai J, Merchant M, Samelko B, Liao Z, Koh KH, Tardi NJ, et al. uPAR isoform 2 forms a dimer and induces severe kidney disease in mice. J Clin Invest (2019) 129:1946–1959
305:
Hahm, E; et al. (December 2016). "Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease". Nature Medicine. 23 (1): 100–106.
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Arnold DT et al. Predicting outcomes of COVID-19 from admission biomarkers: a prospective UK cohort study. Emerg Med J. 2021 May 21;emermed-2020-210380. doi: 10.1136/emermed-2020-210380.
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Enocsson, Helena; Sjöwall, Christopher (April 2015). "Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?". Clinica Chimica Acta. 444: 234–241
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The suPAR level is elevated in patients with cardiovascular diseases compared to healthy individuals. suPAR is a predictor of cardiovascular morbidity and mortality in the general population.
477:
Lyngbaek S, Marott JL, Sehestedt T, et al. Cardiovascular risk prediction in the general population with use of suPAR, CRP, and Framingham Risk Score. Int J Cardiol. 2013;167(6):2904-2911.
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Haastrup E, Grau K, Eugen-Olsen J, Thorball C, Kessing LV, Ullum H. Soluble urokinase plasminogen activator receptor as a marker for use of antidepressants. PLoS One (2014) 9
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with a suPAR below 4 ng/mL indicating low risk of adverse outcomes and a suPAR above 6 ng/mL for high risk of negative outcomes such as severe respiratory failure.
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reflecting the level of activity of the immune system in response to an inflammatory stimulus. suPAR levels positively correlate with pro-inflammatory biomarkers, including
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Meijers B, Poesen R, Claes K et al. Soluble urokinase receptor is a biomarker of cardiovascular disease in chronic kidney disease. Kidney Int 2015 Jan;87(1):210-216.
35:
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Wlazel R, Szwabe K, Guligowska A, Kostka T. Soluble urokinase plasminogen activator receptor level in individuals of advanced age. Sci Rep. 2020; 10: 15462
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42:. uPAR is expressed mainly on immune cells, endothelial cells, and smooth muscle cells. uPAR is a membrane-bound receptor for uPA, also known as
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113:
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Altintas, I., et al. suPAR Cut-Offs for Risk Stratification in Patients With Symptoms of COVID-19. Biomark Insights 2021 Aug 15;16
104:. suPAR is also associated with organ damage in various diseases. Elevated levels of suPAR are associated with increased risk of
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Hayek S, Sever S, Ko Y et al. Soluble urokinase receptor and chronic kidney disease. N Engl J Med. 2015 Nov 12; 373(20):1916-25.
257:
Thunø, Maria; Macho, Betina; Eugen-Olsen, Jesper (2009). "SuPAR: The Molecular Crystal Ball". Disease Markers. 27 (3–4): 157–72
187:. It consists of the three homologous domains D1, D2, and D3. Comparing cDNA sequences, D1 differs from D2 and D3 in its
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Azam et al. Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI J Am Soc Nephrol. 2020 Nov;31(11):2725-2735.
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suPAR is mainly measured in serum and plasma isolated from human venous blood.
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Accession no. AAK31795) is a protein and the soluble form of
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10.3389/fmed.2021.791716. PMID 34926532; PMCID: PMC8674575.
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structure, causing its distinct ligand binding properties.
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links uPAR to the cell membrane making it available for
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incidence of cardiovascular diseases in these patients.
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suPAR has a secondary structure of 17 anti-parallel
28:Soluble urokinase plasminogen activator receptor
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106:systemic inflammatory response syndrome
100:(CRP) and other parameters, including
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566:Clusters of differentiation
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175:Molecular characteristics
541:"suPARnostic® Products"
219:Plasma and serum levels
158:Cardiovascular diseases
94:tumor necrosis factor-α
140:Acute medical patients
118:cardiovascular disease
84:Clinical significance
468:2010;268(3):296-308.
126:infectious diseases
69:cerebrospinal fluid
98:C-reactive protein
75:General population
458:2015;184:631-636.
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539:ViroGates.
376:ViroGates.
88:suPAR is a
571:Biomarkers
555:Categories
236:References
227:Technology
204:GPI-anchor
166:Nephrology
337:69:36–44.
185:α-helices
134:mortality
90:biomarker
44:urokinase
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286:287–296.
193:tertiary
181:β-sheets
149:COVID-19
108:(SIRS),
315:(2010).
296:658–66.
189:primary
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366:(2010)
132:, and
110:cancer
67:, and
53:plasma
65:serum
61:blood
57:urine
32:suPAR
18:SuPAR
202:The
191:and
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40:uPAR
36:NCBI
208:uPA
130:HIV
34:) (
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