Reliability of biomarkers of sepsis during extracorporeal therapies: the clinician needs to know what is eliminated and
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EDITORIAL
Open Access
Reliability of biomarkers of sepsis during extracorporeal therapies: the clinician needs to know what is eliminated and what is not Patrick M. Honore*, Sebastien Redant and David De Bels
Keywords: Removal of biomarkers, CRRT, Procalcitonin, Presepsin, MR-pro-ADM, Endocan, Pentraxin-3, Heparin binding protein, Osteopontin
Background The evolution of renal replacement therapy (RRT) techniques, and the increasing number of critically ill patients receiving extracorporeal therapies, has presented clinicians with a significant problem: if biomarkers are removed by RRT, can they still be considered reliable in their role of guiding diagnosis and treatment? The most commonly used RRT techniques in intensive care units (ICUs) can be classified into three categories: continuous renal replacement therapy (CRRT), intermittent hemodialysis (IHD), and hybrid techniques such as those performed with sorbent devices and plasma exchange (PE). These techniques remove substances from the plasma via convection, adsorption, or a combination of the two. Various factors determine the degree of removal, including molecular weight (MW) and charge, and the type of membrane and RRT technique used. IHD has a cut-off of 5 kDa in most cases and the risk of eliminating biomarkers is small. For CRRT, the cut-off value of the membranes is about 35 kDa, and as a result, filtration of a significant number of biomarkers may occur. New highly adsorptive membranes (HAMs), such as the acrylonitrile 69-surface treated (AN69-ST), are being used more frequently in ICUs [1]. This means that biomarkers with a MW above 35 kDa, while not * Correspondence: [email protected] ICU Department, Centre Hospitalier Universitaire Brugmann, Place Van Gehuchtenplein,4, 1020 Brussels, Belgium
removed by convection, may potentially be removed in a significant quantity by adsorption. With hybrid devices like CytoSorb, removal of hydrophobic substances with a MW up to 55 kDa occurs via selective binding [2]. PE has a cut-off of 1000 kDa and removes not only biomarkers but also a range of other substances including clotting factors and immunoglobulins. Clearance of a substance cannot always be predicted from MW and RRT membrane characteristics alone, highlighting the need for further studies to determine biomarker levels pre- and post-device for different CRRT techniques. For example, the relatively small MW (25 kDa) of high mobility group protein B1 (HMGB1), a damage-associated molecular pattern (DAMP) and marker of outcome, in theory does not prohibit its removal by convection. However, HMGB-1 is not eliminated by convection and is only effectively cleared through adsorption by HAMs like AN69-ST [3]. This occurs because it has a flat shape, and this prevents its passage through a CRRT membrane, despite its small MW. The degree of biomarkers removal by RRT, with the consequent effect on their serum levels, is essential information for clinicians (Fig. 1).
Biomarkers eliminated by CRRT and sorbents C-reactive protein (CRP) is the most
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