Assessment of the association between increasing membrane pore size and endotoxin permeability using a novel experimental dialysis simulation set-up

Abstract

Background: 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. Methods: 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 (PVP pre ) and after (PVP post ) 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.

Enhancement of solute clearance using pulsatile push-pull dialysate flow for the Quanta SC+: A novel clinic-to-home haemodialysis system

“…This approach relies on the fact that, when using ultrapure dialysis fluid, any biological contaminants present in the fluid are retained or adsorbed within the ultrastructure of the membrane wall and do not pass into the blood stream. Clinically used polymer membranes have differing adsorptive capacities [23,38,41] and consequently the potential exists for the transfer of endotoxin fragments and other bacterial substances present in the dialysis fluid into the patient's blood either by convective transfer (back filtration) or by movement down the concentration gradient (back diffusion) [41,42]. The long-term clinical relevance of this remains an unexplored aspect of haemodialysis therapy.…”

“…Briefly, such an approach involves the combination of diffusion with convection [18]. This combination may be achieved either by internal filtration [19], haemodiafiltration (HDF) [20], or by the use of a new generation of membranes, such as medium cut-off membranes, in a conventional dialysis setting [21][22][23][24]. One of the unintended consequences of these approaches is enhanced protein removal [25].…”

“…olHDF offers a number of advantages compared to haemodialysis [27]; however, the technique does not fit well with the simplified use and time flexibility associated with HHD. On the other hand, expanded dialysis using dialysers utilizing medium cut off membranes requires nothing more than a change in dialyser [21][22][23].…”

Chronic Microvascular Complications in Prediabetic States—An Overview

“…For some years, evidence for a correlation between an increased risk of chronic kidney disease (CKD) and diabetic kidney disease (DKD) in prediabetes has been recorded [ 35 , 46 ]. Characteristic features found in 14 cohort studies are summarized in Table 2 [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Half of the studies [ 48 , 49 , 50 , 51 , 52 , 53 , 54 ] were designed mainly to assess the relationship between metabolic syndrome and CKD.…”

Membrane innovation: closer to native kidneys

“…The materials used in contemporary membranes retain endotoxins and other bacterial products by adsorption, which offers a size-independent retention mechanism in addition to the size exclusion mechanism of the membrane. The importance of adsorption as a barrier against endotoxin transfer is evident from the observation that membranes with similar chemical composition but different pore sizes show no difference in permeability to endotoxins and other cytokine-inducing substances [ 50 ].…”