Protein-bound uraemic toxins (PBUTs) cause various deleterious effects in end-stage kidney disease patients, because their removal by conventional haemodialysis (HD) is severely limited by their low free fraction in plasma. Here we provide an experimental validation of the concept that the HD dialytic removal of PBUTs can be significantly increased by extracorporeal infusion of PBUT binding competitors. The binding properties of indoxyl sulfate (IS), indole-3-acetic acid (IAA) and hippuric acid (HIPA) and their binding competitors, ibuprofen (IBU), furosemide (FUR) and tryptophan (TRP) were studied in uraemic plasma. The effect of binding competitor infusion on fractional removal of PBUT was then quantified in an ex vivo single-pass HD model using uraemic human whole blood. The infusion of a combination of IBU and FUR increased the fractional removal of IS from 6.4 ± 0.1 to 18.3 ± 0.4%. IAA removal rose from 16.8 ± 0.3 to 34.5 ± 0.7%. TRP infusion increased the removal of IS and IAA to 10.5 ± 0.1% and 27.1 ± 0.3%, respectively. Moderate effects were observed on HIPA removal. Pre-dialyzer infusion of PBUT binding competitors into the blood stream can increase the HD removal of PBUTs. This approach can potentially be applied in current HD settings.

High-flux dialysis membranes used with bicarbonate dialysis fluid increase the risk of back diffusion of bacterial endotoxin into the blood during hemodialysis. Endotoxin transfer of various synthetic fiber membranes was tested with bacterial culture filtrates using an in vitro system testing both diffusive and convective conditions. Membranes were tested in a simulated dialysis mode with endotoxin challenge material (approximately 420 EU/mL) added to the dialysis fluid, with saline used to model both blood and dialysis fluid. Samples were taken of both blood and dialysis fluid, and analyzed using a kinetic turbidimetric Limulus amoebocyte lysate assay. Endotoxin was found in all of the blood circuit samples, except for the Fresenius Optiflux F200NR(e) and thick-wall membranes. All membranes tested removed approximately 95% of the endotoxin from solution, with the residual approximately 5% recirculating within the dialysis fluid compartment. Endotoxin distribution through the fiber membrane was examined using a fluorescent-labeled endotoxin conjugate. Fluorescence images indicate that adsorption occurs throughout the membrane wall, with the greatest concentration of endotoxin located at the inner lumen. Contact angle analysis was able to show that all membranes exhibit a more hydrophilic lumen and a more hydrophobic outer surface except for the polyethersulfone membranes, which were of equal hydrophobicity. Resulting data indicate that fiber geometry plays an important role in the ability of the membrane to inhibit endotoxin transfer, and that both adsorption and filtration are methods by which endotoxin is retained and removed from the dialysis fluid circuit.

BackgroundConventional peritoneal dialysis fluids (PDFs) consist of ready-to-use solutions with an acidic pH. Sterilization of these fluids is known to generate high levels of glucose degradation products (GDPs). Although several neutral-pH, low-GDP PD solutions have been developed, none are commercially available in the United States. We analyzed pH and GDPs in Delflex Neutral pH (Fresenius Medical Care North America, Waltham, MA, USA), the first neutral-pH PDF to be approved by the US Food and Drug Administration.MethodsWe evaluated whether patients (n = 26; age range: 18 - 78 years) could properly mix the Delflex Neutral pH PDF after standardized initial training. We further analyzed the concentrations of 10 different glucose degradation products in Delflex Neutral pH PDF and compared the results with similar analyses in other commercially available biocompatible PDFs.ResultsAll pH measurements (n = 288) in the delivered Delflex Neutral pH solution consistently fell within the labeled range of 7.0 ± 0.4. Analysis of mixing errors showed no significant impact on the pH results. Delflex Neutral pH, Balance (Fresenius Medical Care, Bad Homburg, Germany), BicaVera (Fresenius Medical Care), and Gambrosol Trio (Gambro Lundia AB, Lund, Sweden) exhibited similar low total GDP concentrations, with maximums in the 4.25% solutions of 88 μmol/L, 74 μmol/L, 74 μmol/L, and 79 μmol/L respectively; the concentration in Physioneal (Baxter Healthcare Corporation, Deerfield, IL, USA) was considerably higher at 263.26 μmol/L The total GDP concentration in Extraneal (Baxter Healthcare Corporation) was 63 μmol/L, being thus slightly lower than the concentrations in the 4.25% glucose solutions, but higher than the concentrations in the 1.5% and 2.5% glucose solutions.ConclusionsThe new Delflex Neutral pH PDF consistently delivers neutral pH with minimal GDPs.

Sterilized hollow-fiber membranes are used in hemodialysis, ultrafiltration, bioprocessing, and tissue engineering applications that require a stable and biocompatible surface. In this study, we demonstrated significant changes in the fiber physicochemical properties with different methods of sterilization. Commercial polysulfone (PS) hollow fibers containing poly(vinyl pyrrolidone) were subjected to standard ethylene oxide (ETO), sodium hypochlorite (bleach), and electron-beam (e-beam) sterilization techniques followed by analysis of the surface hydrophilicity, morphology, and water-retention ability. E-beam sterilization rendered more hydrophilic fibers with water contact angles near 47 compared to the ETO-and bleachtreated fibers, which were each near 56. Atomic force microscopy revealed lumen root mean square (rms) roughness values near 19 nm for all three sterilization methods;however, e-beam-sterilized and bleach-treated fibers had significantly higher ($ 106 nm) rms values for the outer wall compared to the ETO-sterilized fibers ($ 39 nm). The increased hydrophilicity and surface area of the e-beamsterilized fiber were reflected by a greater water evaporation rate than that of the ETO-treated fiber. These results demonstrate that common sterilization methods may significantly and distinctly alter the polymer membrane physicochemical properties, which may, in turn, impact the performance and, in particular, surface fouling. For tissue engineering and bioprocessing applications, these changes may be leveraged to promote cell adhesion and spreading.

During hemodialysis bacterial lipopolysaccharide (LPS) in contaminated dialysate solution may translocate across the hollow fiber membrane (HFM) to a patient's blood, resulting in fever and possible systemic shock. This study investigates LPS transfer across, and adsorption within, native and modified Fresenius Optiflux® F200NRe polysulfone (PS)/polyvinyl pyrrolidone (PVP) HFMs. Modifications include varied PVP content, addition of a PS‐poly(ethylene glycol) copolymer (PS‐PEG), and bleach sterilization. Under clinically relevant flow conditions LPS from >400 EU mL−1 spiked dialysate is not detected (<0.1 EU mL−1) in the lumens of native fibers, but is detected to varying degrees (0.2–15 EU mL−1) in the lumens of the modified fibers. Fluorescently labeled LPS predominantly adsorbs near the lumen of all membranes except the PS‐PEG containing membrane, where LPS localizes on the outer wall. Thus, addition of PS‐PEG may entrap LPS in the HFM spongy matrix, away from the blood‐contacting fiber lumen. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41550.