Effects of Different Levels of Endotoxin Contamination on Inflammatory Cytokine Production by Peripheral Blood Mononuclear Cells after High-Flux Hemodialysis

Praditpornsilpa, Kearkiat; Tiranathanagul, Khajohn; Susantitaphong, Paweena; Katavetin, Pisut; Trakarnvanich, Thananda; Townamchai, Natavudh; Kanjanabuch, Talerngsak; Avihingsanon, Yingyos; Tungsanga, Kriang; Eiam‐Ong, Somchai

doi:10.1159/000324394

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…Many different contaminants are formed as a result of bacterial degradation and not all are detectable using the LAL assay. Nevertheless, LPS contamination of dialysis fluid of between up to 2 EU/mL and up to 7.68 EU/mL has been detected using the LAL assay 9,16 . A combined method using LAL and silkworm larvae plasma has detected PG levels of between 4.1 and 20 ng/mL in dialysis fluid from a central supply system 17 and individual units 9 .…”

Section: Discussionmentioning

confidence: 99%

Pyrogen retention: Comparison of the novel medium cut-off (MCO) membrane with other dialyser membranes

Hulko

Dietrich

Koch

et al. 2019

Sci Rep

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Haemodialysis effectively removes small solutes and smaller-sized middle molecules from the blood; however, the clearance of larger middle molecules, which have been associated with negative effects, is poor. The novel medium cut-off (MCO) dialysis membrane has larger pore sizes and a more open structure than other high-flux membranes, providing improved removal of larger middle molecules while retaining albumin. However, larger pore sizes may potentially increase permeability to pyrogens, including endotoxins and other bacterial contaminants, that could be present in the dialysis fluid. In this study, we tested the capacity of low-flux, high-flux, MCO and high cut-off dialyser membranes with different pore sizes to prevent pyrogens crossing from dialysate to the blood side in a closed-loop test system, differentiating among lipopolysaccharides, peptidoglycans and bacterial DNA using a toll-like receptor assay. Even though the bacterial contamination levels in our test system exceeded the acceptable pyrogen dose for standard dialysis fluid, levels of lipopolysaccharides, peptidoglycans and bacterial DNA in the blood-side samples were too low to identify potential differences in pyrogen permeability among the membranes. Our results suggest that MCO membranes are suitable for haemodialysis using ISO standard dialysis fluid quality, and retain endotoxins at a similar level as other membranes.

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Section: Discussionmentioning

confidence: 99%

Pyrogen retention: Comparison of the novel medium cut-off (MCO) membrane with other dialyser membranes

Hulko

Dietrich

Koch

et al. 2019

Sci Rep

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“…The microbiological quality of the water in the dialysate used in hemodialysis treatment has been suggested as a major contributor to the inflammatory status in this group of patients with the background idea that microbiologic contaminants in the dialysate and level of endotoxin might induce inflammation and resistance to ESA in dialysis patients. [ 10 , 11 ]…”

Section: Discussionmentioning

confidence: 99%

“…They stated that chronic inflammation in HD is strongly associated with water quality and can be assessed by measuring the concentrations of endotoxin in the dialysate. [ 11 ]…”

Section: Discussionmentioning

confidence: 99%

Impact of water treatment on anemia in hemodialysis patients

El-Sharabasy,

Hassan,

Hebah

et al. 2023

Indian J Nephrol

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Introduction: The microbiological quality of water in the dialysate used in hemodialysis has been suggested as a contributor to inflammation, and a link between dialysate purity, inflammation, and responsiveness to erythropoietin therapy has been suggested in many studies. The level of endotoxin might induce inflammation and resistance to erythropoietin therapy in dialysis patients. We aimed to compare the effect of using the central dialysis fluid delivery system (CDDS) versus the single-patient dialysis fluid delivery system (SPDDS) on anemia in prevalent hemodialysis patients. Methods: In a prospective cohort study, 100 adult prevalent hemodialysis patients with T-SAT ≥20% were divided into two equal groups: CDDS and SPDDS. Endotoxin in water sample and routine investigations (hemoglobin, serum Ca+, serum Po4−, PTH, and urea level) were done. CRP, erythropoietin resistivity index (ERI), and erythropoietin stimulating agents (ESAs) doses were assessed repeatedly to assess inflammatory and anemia states. Results: Endotoxin level in the dialysis fluid of the CDDS group was significantly lower compared to the SPDDS group (0.05 vs. 0.11 EU/ml, P = 0.001). CRP level decreased significantly after 3 months in the CDDS group ( P < 0.001) compared to the SPDDS group ( P = 0.54), with significant improvement in the hemoglobin level and ERI at 3 months in the CDDS group and decrease in ESA requirements. Conclusion: Improvement in dialysis liquid purity reduces inflammatory markers in prevalent hemodialysis patients, improves ERI, and decreases ESA requirements in renal anemia.

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“…THP1 and U937 cell lines were obtained from American Type Culture Collection, Manassas, VA, USA. PBMCs were isolated from the peripheral blood of 4 healthy male donors using a Ficoll gradient as described [ 18 , 19 ]. Cells were cultured in RPMI-1640 (Biolot, Saint-Petersburg, Russia) supplemented using 20% fetal bovine serum (FBS) (GE Healthcare Life Sciences, Russia), 100 units/mL penicillin, and 100 µg/mL streptomycin (Biolot, Russia) at 37 °C, 5% CO 2 in humidified atmosphere.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes

Kokinos,

Tsymbal,

Galochkina

et al. 2023

Viruses

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Hyperactivation of the immune system remains a dramatic, life-threatening complication of viral and bacterial infections, particularly during pneumonia. Therapeutic approaches to counteract local and systemic outbreaks of cytokine storm and to prevent tissue damage remain limited. Cyclin-dependent kinases 8 and 19 (CDK8/19) potentiate transcriptional responses to the altered microenvironment, but CDK8/19 potential in immunoregulation is not fully understood. In the present study, we investigated how a selective CDK8/19 inhibitor, Senexin B, impacts the immunogenic profiles of monocytic cells stimulated using influenza virus H1N1 or bacterial lipopolysaccharides. Senexin B was able to prevent the induction of gene expression of proinflammatory cytokines in THP1 and U937 cell lines and in human peripheral blood-derived mononuclear cells. Moreover, Senexin B substantially reduced functional manifestations of inflammation, including clustering and chemokine-dependent migration of THP1 monocytes and human pulmonary fibroblasts (HPF).

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Effects of Different Levels of Endotoxin Contamination on Inflammatory Cytokine Production by Peripheral Blood Mononuclear Cells after High-Flux Hemodialysis

Cited by 8 publications

References 28 publications

Pyrogen retention: Comparison of the novel medium cut-off (MCO) membrane with other dialyser membranes

Pyrogen retention: Comparison of the novel medium cut-off (MCO) membrane with other dialyser membranes

Impact of water treatment on anemia in hemodialysis patients

Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes

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