Biomarkers of sepsis during continuous dialysis

This is an automatically translated article.

Posted by Dr. Truong Ngoc Hai - Resuscitation Doctor - Emergency Department - Vinmec Central Park International General Hospital

Today, with nearly 180 biomarkers have been identified, many biomarkers are being used by doctors to detect, monitor progress, evaluate prognosis of bacterial infections, sepsis and decided to stop taking antibiotics. However, these biomarkers may be eliminated during continuous dialysis, affecting the confidence in determining the severity of the infection. Until now, experts are still trying to find new biomarkers that are not eliminated by CRRT.

1. The most frequently used biomarkers in clinical practice

1.1. C-reactive Protein

C-reactive Protein (CRP) is mainly present as a monomer (mCRP) in the blood of patients with sepsis [5], which, due to its relatively small molecular weight (22-25 kDa) should be eliminated in all cases. all CRRT methods [4]. In addition, a significant amount of mCRP was also adsorbed on the membrane [2, 6]. Currently, many ICUs use filters with high adsorption capacity to increase mCRP clearance. Plasma concentrations of C-reactive Protein can be artificially low during CRRT, making CRP levels unreliable in the diagnosis or assessment of infection during CRRT [7].

1.2. Procalcitonin (PCT)

In sepsis patients undergoing continuous venous hemodialysis (CVVH), PCT was detected in the ultrafiltration fluid of all patients [10]. Most PCT is eliminated via convection, but the adsorption mechanism also contributes to PCT clearance during the first hours of therapy [10]. The use of filters with high adsorption capacity further increased the clearance of CRP and PCT [6, 11].

1.3. Brain Natriuretic Factors

Biomarkers BNP and NT-proBNP have been applied recently in sepsis. Both biomarkers BNP and NT-proBNP are eliminated very readily by high-flux and low-flux membranes in CRRT due to their low molecular size [13], [14].

2. Cytokine/Chemokine biomarkers in sepsis

2.1. High Mobility Group 1 Protein (HMGB-1)

Although HMGB-1 has a relatively low molecular weight, HMGB-1 could theoretically be eliminated by convection filtration. However, in fact, HMGB-1 is only effectively eliminated via adsorption mechanism by filters with high adsorption capacity, especially acrylonitrile 69 (AN69-ST) surface-treated membranes [15] ].

2.2. Osteopontin

Osteopontin is a negatively charged protein, with a molecular weight of about 32 kDa. There is no convincing evidence that continuous hemodialysis can clear osteopontin from the circulation [16]. However, CRRT uses new types of membranes, such as the AN69-ST membrane – due to its surface covered with a polyethylene biopolymer layer, it has a high positive charge density, in addition to its biocompatibility and high permeability, the membrane It also has a strong adsorption capacity, so it can increase the excretion of Osteopontin [6].

3. Biomarkers in sepsis associated with vascular endothelial damage – Endocan

Endocan is a novel endothelial-derived soluble dermatan sulfate proteoglycan with a molecular mass of about 15-40 kDa [17, 18]. Modern CRRT membranes can remove substances with molecular weights up to 35 kDa. When using a new filter with high adsorption capacity, the elimination of endocan through CRRT is increased [6]. Therefore, the confidence level of endocans in CRRT may be altered.

4. Biomarker in vasodilatation-associated sepsis – Proadrenomedullin (MR-proADM)

The molecular weight of MR-proADM is between 4 and 5.5 kDa, so it can also be removed by CRRT. The study by Mueller et al showed a significant reduction of MR-proADM (45.65%) if high-flux membranes were used [20] (especially with the 35 kDa filtration threshold of existing CRRT membranes). great [6]). More studies are needed to determine whether or not MR-proADM is eliminated by convection in CRRT.

5. Other biomarkers in the acute phase – Pentraxin

Pentraxin-3 (PTX3) is a glycoprotein released by endothelial and inflammatory cells upon activation of cytokines and endotoxins. PTX3 better reflects inflammation of local blood vessels and bacterial load than CRP [23]. Therefore, PTX3 may be a more appropriate marker than CRP in terms of severity and prognosis of necrotizing soft tissue infection. As reported by Hansen, there was a statistically significant association between high PTX3 levels and the occurrence of septic shock, amputation, the need for dialysis, and the risk of death in patients with tissue necrosis infection. soft [23].
In most patients, PTX3 in plasma is monomeric with a molecular weight of about 35 kDa [23] and can therefore theoretically be eliminated by CRRT. Recently, Schilder et al. demonstrated that although PTX3 is slightly adsorbed, the CVVH mode does not eliminate PTX3 by convection, resulting in unchanged plasma PTX3 concentrations [24]. It is necessary to further study the possibility of increasing the elimination of PTX3 with the CVVH method using membranes with high adsorption properties [24, 25].

6. Biomarkers of cell markers in sepsis – Presepsin

Recently, sCD14-ST, also known as presepsin, has been identified as a potential biomarker of sepsis [26]. Presepsin is fragmented from a larger glycoprotein and has a molecular weight of about 13 kDa. The clearance of presepsin may be even higher than expected because the molecule can "stick" to a highly adsorbent filter [6].

7. Biomarkers of blood coagulation in sepsis - Heparin Binding Protein

Heparin Binding Protein (HBP), also known as a positively charged antimicrobial protein, has a molecular weight of 37 kDa [28] and can therefore be eliminated by CRRT via a convection mechanism [6]. Using membranes with high adsorption capacity can enhance HBP removal through adsorption [6].
The following table summarizes all biomarkers described in this review with information on molecular weight, clearance by convection and/or adsorption, noting the available research. and need more research. Thereby showing that all biomarkers can be eliminated via CRRT, especially when using a filter with high adsorption capacity. Therefore, there are no biomarkers that accurately reflect the infection status in patients undergoing CRRT. More studies are needed to evaluate and find new biomarkers that reliably reflect the infection status during CRRT. This task becomes even more complicated when the filter with high adsorption capacity has raised the filtration threshold up to 65 kDa.

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