Analytical, biochemical and clearance considerations of soluble urokinase plasminogen activator receptor (suPAR) in healthy individuals

Soluble urokinase plasminogen activator receptor (suPAR) is an emerging marker of cardiovascular disease burden. Appropriate assessment of assay performance and reference interval are required to enable interpretation of results to facilitate its clinical application. suPAR was measured using the su...

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Bibliographic Details
Published in:Clinical biochemistry Vol. 69; pp. 36 - 44
Main Authors: Chew-Harris, Janice, Appleby, Sarah, Richards, A. Mark, Troughton, Richard W., Pemberton, Christopher J.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.07.2019
Subjects:
Adult
Chromatography, Gel - methods
Chromatography, High Pressure Liquid - methods
Clearance
Enzyme-Linked Immunosorbent Assay
Female
Healthy Volunteers
Humans
Limit of Detection
Male
Middle Aged
Molecular Weight
Receptors, Urokinase Plasminogen Activator - blood
Receptors, Urokinase Plasminogen Activator - chemistry
Reference interval
Reference Standards
suPAR
Reference interval
Clearance
suPAR
Molecular weight
ISSN:0009-9120, 1873-2933, 1873-2933
Online Access:Get full text
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Summary:Soluble urokinase plasminogen activator receptor (suPAR) is an emerging marker of cardiovascular disease burden. Appropriate assessment of assay performance and reference interval are required to enable interpretation of results to facilitate its clinical application. suPAR was measured using the suPARnostic® ELISA in 155 healthy volunteers. Assay performance was assessed for anticoagulant effect, recovery, interference, linearity and cross-reactivity. The identity of immunoreactive suPAR was confirmed by size-exclusion HPLC. To establish anatomical sites of release and uptake, we measured suPAR in regional samples from subjects undergoing cardiac catheterization. The median concentration of suPAR was 2.1 ng/mL (IQR:1.7–2.3) in health. In comparison with EDTA, suPAR measurements were affected by lithium heparin (>10% change) and increased with serum usage. suPAR reactivity also increased in the presence of haemolysis (10 g/L), but was suppressed with urokinase and lipids (4 g/L). In multiple regression analyses, suPAR associated independently with body weight, NT-proBNP and MR-proADM (P = .03) for healthy individuals. Regional plasma sampling showed lower suPAR concentrations in the coronary sinus and renal vein compared with concentrations in femoral arterial samples. Immunoreactive circulating suPAR species had Mr of 10–39 kDa. The suPARnostic® assay performs acceptably for a clinical assay but is limited in the presence of high levels of hemolysis, lipids and urokinase. We provide the first evidence for the heart and kidneys as organs of suPAR clearance in humans. Additional investigations are warranted to determine whether there is a need to compare the marker performance of differing circulating forms of suPAR.
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ISSN:0009-9120
1873-2933
1873-2933
DOI:10.1016/j.clinbiochem.2019.05.010