Abstract
BackgroundMembranes 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.MethodsDialysis 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.ResultsThe 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.ConclusionsA 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.
Highlights
Membranes with increasing pore size are introduced to enhance removal of large uremic toxins with regular hemodialysis
Compatibility of PVP dissolved in PBS (PVPPBS) with both the Limulus Amebocyte Lysate (LAL)-assay and THP-1 assay was evaluated per se and in combination with LPS in comparison to PBS
Assay compatibility of PVP PVP dissolved in PBS (PVPPBS) at a concentration of 12.5 g/L was evaluated for its possible interference with both the LAL-assay and the THP-1 assay
Summary
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. Membranes with a steeper cut-off at a lower molecular weight level than the HCO membranes, the so-called medium cutoff (MCO) membranes, have been introduced [17] These membranes can even remove large toxins such as kappa and lambda free light chains [18], two compounds associated with inflammatory markers and mortality in CKD [19,20,21,22]. In this study, ultrapure dialysate was used [23]
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