Membranes with increasing pore size are introduced to enhance removal of large uremic toxins with regular hemodialysis. These membranes might theoretically have higher permeability for bacterial degradation products. In this paper, permeability for bacterial degradation products of membranes of comparable composition with different pore size was investigated with a new in vitro set-up that represents clinical flow and pressure conditions.
Dialysis was simulated with an AK200 machine using a low-flux, high-flux, medium cut-off (MCO) or high cut-off (HCO) device (n = 6/type). A polyvinylpyrrolidone-solution (PVP) was recirculated at blood side. At dialysate side, a challenge solution containing a filtrated lysate of two water-borne bacteria (Pseudomonas aeruginosa and Pelomononas saccharophila) was infused in the dialysate flow (endotoxin ≥ 4EU/ml). Blood and dialysate flow were set at 400 and 500 ml/min for 60 min. PVP was sampled before (PVPpre) and after (PVPpost) the experiment and dialysate after 5 and 55 min. Limulus Amebocyte Lysate (LAL) test was performed. Additionally, samples were incubated with a THP-1 cell line (24 h) and IL-1β levels were measured evaluating biological activity.
The LAL-assay confirmed presence of 9.5 ± 7.4 EU/ml at dialysate side. For none of the devices the LAL activity in PVPpre vs. PVPpost was significantly different. Although more blood side PVP solutions had a detectable amount of endotoxin using a highly sensitive LAL assay in the more open vs traditional membranes, the permeability for endotoxins of the 4 tested dialysis membranes was not significantly different but the number of repeats is small. None of the PVP solutions induced IL-1β in the THP-1 assay.
A realisitic in vitro dialysis was developed to assess membrane translocation of bacterial products. LAL activity on the blood side after endotoxin exposure did not change for all membranes. Also, none of the PVPpost solutions induced IL-1β in the THP-1 bio-assay.
Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Intl. 1999;55(2):648–58. CrossRef
Vanholder R, De Smet R, Hsu C, Vogeleere P, Ringoir S. Uremic toxicity: the middle molecule hypothesis revisited. Semin Nephrol. 1994;14(3):205–18. PubMed
Haase M, Bellomo R, Baldwin I, Haase-Fielitz A, Fealy N, Morgera S, et al. Beta2-microglobulin removal and plasma albumin levels with high cut-off hemodialysis. Int J Artif Organs. 2007;30(5):385–92. PubMed
Girndt M, Fiedler R, Martus P, Pawlak M, Storr M, Bohler T, et al. High cut-off dialysis in chronic haemodialysis patients. Eur J Clin Investig. 2015;45(12):1333–40. CrossRef
Kirsch AH, Lyko R, Nilsson LG, Beck W, Amdahl M, Lechner P, et al. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol Dial Transplant. 2017;32(1):165–72. PubMed
Quality of dialysis fluid for haemodialysis and related therapies. ISO 11663:2014(E) 2014.
Hulko M, Gekeler A, Koch I, Dietrich V, Krause B. Dialysis membrane pore size does not determine LPS retention. Nephrol Dial Transplant. 2015;30(suppl 3)
Lowe GD, Lee AJ, Rumley A, Price JF, Fowkes FG. Blood viscosity and risk of cardiovascular events: the Edinburgh artery study. Br J Haemat. 1997;96(1):168–73. CrossRef
Eloot S, De Wachter D, Vienken J, Pohlmeier R, Verdonck P. In vitro evaluation of the hydraulic permeability of polysulfone dialysers. Int J Artif Organs. 2002;25(3):210–6. PubMed
Ogden TL. Handling results below the level of detection. Ann Occup Hyg. 2010;54(3):255–6. PubMed
Convention USP: General Chapter <85> Bacterial Endotoxins Test. In: United States Pharmacopeia [USP]. edn.
Gong D, Ji D, Zhang K, Huang X, Huang G, Xu B, Liu Z. Endotoxemia after high cutoff hemodialysis for treatment of patient with multiple myeloma can be prevented by using ultrapure dialysate: a case report. Hemodial Int. 2013;17(4):618–23. PubMed
Ronco C. Fluid mechanics and Crossfiltration in hollow-fiber Hemodialyzers. In: Ronco C, Canaud B, Aljama P, editors. Hemodiafiltration, vol. 158. Basel: Karger; 2007. p. 34–49. CrossRef
Schneditz D, Zierler E, Vanholder R, Eloot S. Internal filtration, filtration fraction, and blood flow resistance in high- and low-flux dialyzers. Clin Hemorheol Microcirc. 2014;58(3):455–69. PubMed
Vanholder R. Biocompatibility issues in hemodialysis. Clinical. Mater. 1992;10(1–2):87–133.
- Assessment of the association between increasing membrane pore size and endotoxin permeability using a novel experimental dialysis simulation set-up
Wim Van Biesen
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II