Adsorption kinetics of high mobility group box 1 protein in a polyacrylonitrile hemofiltration membrane

Nakamura, Tomoyuki; Moriyama, Kazuhiro; Shimomura, Yoshiharu; Kato, Yu; Kuriyama, Naohide; Hara, Yoshitaka; Yamada, Shingo; Nishida, Osamu

doi:10.1111/1744-9987.13489

Cited by 12 publications

(13 citation statements)

References 26 publications

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“…The adsorption phenomenon by the PMMA membrane is thought to be due to the occlusions of protein molecules in specific sizes into the pore of the membrane micropores [14]. In contrast, the AN69ST membrane is a hydrogel membrane with a strong negative charge layer, and the principle of substance adsorption is ion adsorption between the negative charge of the membrane and the positive charge of the target substance [5,15]. Although the adsorption characteristics of cytokines by these two types of membranes have been clarified [11–16], there have been no reports on myoglobin.…”

Section: Discussionmentioning

confidence: 99%

Comparison of myoglobin clearance in three types of blood purification modalities

et al. 2021

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Myoglobin, which can cause acute kidney injury, has a relatively high molecular weight and is poorly cleared by diffusion. We compared and examined myoglobin clearance by changing the blood purification membrane and modality in patients with a myoglobin blood concentration ≥ 1000 ng/ml. We retrospectively analyzed three patient groups based on the following three types of continuous hemofiltration (CHF): AN69ST membrane, polymethylmethacrylate (PMMA) membrane, and high‐flow hemodiafiltration (HDF) with increased dialysate flow rate using the PMMA membrane. There was no significant difference in clearance in CHF between AN69ST and PMMA membranes. However, the high‐flow HDF group showed the highest myoglobin clearance (p = 0.003). In the PMMA membrane, changing the treatment modality to high‐flow HDF increased clearance above the theoretical value, possibly due to internal filtration. To remove myoglobin by kidney replacement therapy from patients with hypermyoglobinemia, a modality such as high‐flow HDF would be desirable.

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Section: Discussionmentioning

confidence: 99%

Comparison of myoglobin clearance in three types of blood purification modalities

et al. 2021

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“…Additionally, HMGB1 with a molecular weight of approximately 30,000 did not saturate the AN69ST membrane. When HMGB1 was repeatedly added seven times during hemofiltration, a rapid decrease in circulating HMGB1 was observed after every addition, with no signs of saturation [112]. The AN69ST membrane with adsorbed HMGB1 was observed using immunoelectron microscopy.…”

Section: Figurementioning

confidence: 98%

“…Further, continuous hemo(dia)filtration (CH(D)F) has a history of being performed not only to replace renal function, but also to prevent or treat organ damage through the removal of inflammatory mediators in Japan [109]. However, prior to our in vitro study [110][111][112], little was known about the quantity of cytokines adsorbed on the cytokine adsorption membrane and the mechanism of adsorption. In the principle of membrane filtration, only substances smaller than the membrane pores can be removed.…”

Section: Cytokine-adsorbing Hemofiltermentioning

confidence: 99%

“…Even when a high concentration of HMGB1 was adsorbed, HMGB1 was observed on the surface of the membrane and in some bulk layers. Thus, the membrane surface was identified to be too large for saturation to occur [112]. Furthermore, changing the hydrogen ion concentration of the test solution at each step in cytokine adsorption experiments revealed that ionic binding was the mechanism employed for cytokine adsorption by the AN69ST membrane (negatively charged) [111].…”

Section: Figurementioning

confidence: 99%

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Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

Moriyama

Nishida

2021

IJMS

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Sepsis is characterized by a dysregulated immune response to infections that causes life-threatening organ dysfunction and even death. When infections occur, bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns, bind to pattern recognition receptors, such as toll-like receptors, to initiate an inflammatory response for pathogen elimination. However, strong activation of the immune system leads to cellular dysfunction and ultimately organ failure. Damage-associated molecular patterns (DAMPs), which are released by injured host cells, are well-recognized triggers that result in the elevation of inflammatory cytokine levels. A cytokine storm is thus amplified and sustained in this vicious cycle. Interestingly, during sepsis, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. Thus, the concept of blood purification has evolved to include inflammatory cells and mediators. In this review, we summarize recent advances in knowledge regarding the role of lipopolysaccharides, cytokines, DAMPs, and neutrophils in the pathogenesis of sepsis. Additionally, we discuss the potential of blood purification, especially the adsorption technology, for removing immune cells and molecular mediators, thereby serving as a therapeutic strategy against sepsis. Finally, we describe the concept of our immune-modulating blood purification system.

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“…However, there is only limited evidence that high-volume hemofiltration improves outcomes in critically ill patients [8,9]. On the other hand, polyacrylonitrile (AN69) filter membranes have been shown to have a high capacity to adsorb cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and IL-10) and high mobility group box-1, a representative of damage-associated molecular patterns in experimental studies [10][11][12]. The membrane is negatively charged from methallylsulfonate, adsorbing cytokines via ionic bonding between the sulfonate groups and amino groups on the cytokines.…”

Section: Introductionmentioning

confidence: 99%

AN69 Filter Membranes with High Ultrafiltration Rates during Continuous Venovenous Hemofiltration Reduce Mortality in Patients with Sepsis-Induced Multiorgan Dysfunction Syndrome

Lee

Tsai

et al. 2021

Membranes

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Polyacrylonitrile (AN69) filter membranes adsorb cytokines during continuous venovenous hemofiltration (CVVH). Although high-volume hemofiltration has shown limited benefits, the dose-effect relationship in CVVH with AN69 membranes on severe sepsis remains undetermined. This multi-centered study enrolled 266 patients with sepsis-induced multiorgan dysfunction syndrome (MODS) who underwent CVVH with AN69 membranes between 2014 and 2015. We investigated the effects of ultrafiltration rates (UFR) on mortality. We categorized patients that were treated with UFR of 20–25 mL/kg/h as the standard UFR group (n = 124) and those that were treated with a UFR >25 mL/kg/h as the high UFR group (n = 142). Among the patient characteristics, the baseline estimated glomerular filtration rates (eGFR) <60 mL/min/1.73 m2, hemoglobin levels <10 g/dL, and a sequential organ failure assessment (SOFA) score ≥15 at CVVH initiation were independently associated with in-hospital mortality. In the subgroup analysis, for patients with SOFA scores that were ≥15, the 90-day survival rate was higher in the high UFR group than in the standard UFR group (HR 0.54, CI: 0.36–0.79, p = 0.005). We concluded that in patients with sepsis-induced MODS, SOFA scores ≥15 predicted a poor rate of survival. High UFR setting >25 mL/kg/h in CVVH with AN69 membranes may reduce the mortality risk in these high-risk patients.

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Adsorption kinetics of high mobility group box 1 protein in a polyacrylonitrile hemofiltration membrane

Cited by 12 publications

References 26 publications

Comparison of myoglobin clearance in three types of blood purification modalities

Comparison of myoglobin clearance in three types of blood purification modalities

Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

AN69 Filter Membranes with High Ultrafiltration Rates during Continuous Venovenous Hemofiltration Reduce Mortality in Patients with Sepsis-Induced Multiorgan Dysfunction Syndrome

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