Time-resolving characterization of molecular weight retention changes among three synthetic high-flux dialyzers.

BACKGROUND: Toxin removal capacity (i.e., performance) of a dialyzer is not constant but diminishes during treatment, as the adsorption of proteins to the membrane provides an additional barrier to uremic solutes. We investigated time-resolving molecular weight retention changes among synthetic high-flux dialyzers and compared the results with recent data from a randomized controlled trial. METHODS: In plasma recirculation experiments over 240 min, sieving coefficients (SC) for ß2-microglobulin, myoglobin, and albumin were determined for the FX CorAL (Fresenius Medical Care), ELISIO (Nipro), and xevonta (B. Braun). Molecular weight retention (MWR) curves were generated and the shifts over 120 min were characterized. Effective pore radius was determined, and the predicted albumin loss was compared with clinical data. RESULTS: SC decreased over time for all dialyzers (mean relative decrease across all dialyzers: ß2-microglobulin: 8.0% (120 min); myoglobin: 56.6% (240 min); albumin: 94.1% (240 min)). FX CorAL (7.3%, 52.6% and 91.1%) and ELISIO (7.7%, 51.0%, and 93.8%) showed a lower decrease than xevonta (9.0%, 66.2%, and 97.4%). For all dialyzers, MWR curves shifted toward lower molecular weight, with the lowest shift for FX CorAL (by 0.23 nm at SC50%, 120 min) and highest for xevonta (0.50 nm). FX CorAL had the highest slope over time and the smallest decrease in the effective pore radius (2 min: 2.31 nm, 120 min: 2.08 nm). Predicted albumin loss over 4 h was highest for xevonta (609.3 mg) and comparable between ELISIO (283.6 mg) and FX CorAL (313.3 mg). CONCLUSIONS: Substantial differences in the temporal performance profile of dialyzers exist. The present approach allows the characterization of dialyzer permeability changes over time using standard, clinically relevant protein markers.

Complement activation by dialysis membranes and its association with secondary membrane formation and surface charge.

Activation of the complement system may occur during blood-membrane interactions in hemodialysis and contribute to chronic inflammation of patients with end-stage renal disease. Hydrophilic modification with polyvinylpyrrolidone (PVP) has been suggested to increase the biocompatibility profile of dialysis membranes. In the present study we compared the complement activation of synthetic and cellulose-based membranes, including the polysulfone membrane with α-tocopherol-stabilized PVP-enriched inner surface of the novel FX CorAL dialyzer, and linked the results to their physical characteristics. Eight synthetic and cellulose-based dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO, SUREFLUX [Nipro]; xevonta [B. Braun]; FDX [Nikkisio Medical]) were investigated in the present study. Complement activation (C3a, C5a, and sC5b-9) was evaluated in a 3 hours ex vivo recirculation model with human blood. Albumin sieving coefficients were determined over a 4 hours ex vivo recirculation model with human plasma as a surrogate of secondary membrane formation. Zeta potential was measured as an indicator for the surface charge of the membranes. The FX CorAL dialyzer induced the lowest activation of the three complement factors (C3a: -39.4%; C5a: -57.5%; and sC5b-9: -58.9% compared to the reference). Highest complement activation was found for the cellulose-based SUREFLUX (C3a: +154.0%) and the FDX (C5a: +335.0% and sC5b-9: +287.9%) dialyzers. Moreover, the FX CorAL dialyzer had the nearest-to-neutral zeta potential (-2.38 mV) and the lowest albumin sieving coefficient decrease over time. Albumin sieving coefficient decrease was associated with complement activation by the investigated dialyzers. Our present results indicate that the surface modification implemented in the FX CorAL dialyzer reduces the secondary membrane formation and improves the biocompatibility profile. Further clinical studies are needed to investigate whether these observations will result in a lower inflammatory burden of hemodialysis patients.

Hydrophilic Modification of Dialysis Membranes Sustains Middle Molecule Removal and Filtration Characteristics.

While efficient removal of uremic toxins and accumulated water is pivotal for the well-being of dialysis patients, protein adsorption to the dialyzer membrane reduces the performance of a dialyzer. Hydrophilic membrane modification with polyvinylpyrrolidone (PVP) has been shown to reduce protein adsorption and to stabilize membrane permeability. In this study we compared middle molecule clearance and filtration performance of nine polysulfone-, polyethersulfone-, and cellulose-based dialyzers over time. Protein adsorption was simulated in recirculation experiments, while ß2-microglobulin clearance as well as transmembrane pressure (TMP) and filtrate flow were determined over time. The results of this study showed that ß2-microglobulin clearance (-7.2 mL/min/m2) and filtrate flow (-54.4 mL/min) decreased strongly during the first 30 min and slowly afterwards (-0.7 mL/min/m2 and -6.8 mL/min, respectively, for the next 30 min); the TMP increase (+37.2 mmHg and +8.6 mmHg, respectively) showed comparable kinetics. Across all tested dialyzers, the dialyzer with a hydrophilic modified membrane (FX CorAL) had the highest ß2-microglobulin clearance after protein fouling and the most stable filtration characteristics. In conclusion, hydrophilic membrane modification with PVP stabilizes the removal capacity of middle molecules and filtration performance over time. Such dialyzers may have benefits during hemodiafiltration treatments which aim to achieve high exchange volumes.

Hemodiafiltration: Technical and Medical Insights.

Despite the significant medical and technical improvements in the field of dialytic renal replacement modalities, morbidity and mortality are excessively high among patients with end-stage kidney disease, and most interventional studies yielded disappointing results. Hemodiafiltration, a dialysis method that was implemented in clinics many years ago and that combines the two main principles of hemodialysis and hemofiltration-diffusion and convection-has had a positive impact on mortality rates, especially when delivered in a high-volume mode as a surrogate for a high convective dose. The achievement of high substitution volumes during dialysis treatments does not only depend on patient characteristics but also on the dialyzer (membrane) and the adequately equipped hemodiafiltration machine. The present review article summarizes the technical aspects of online hemodiafiltration and discusses present and ongoing clinical studies with regards to hard clinical and patient-reported outcomes.

Impact of Hydrophilic Modification of Synthetic Dialysis Membranes on Hemocompatibility and Performance.

The dialyzer is the core element in the hemodialysis treatment of patients with end-stage kidney disease (ESKD). During hemodialysis treatment, the dialyzer replaces the function of the kidney by removing small and middle-molecular weight uremic toxins, while retaining essential proteins. Meanwhile, a dialyzer should have the best possible hemocompatibility profile as the perpetuated contact of blood with artificial surfaces triggers complement activation, coagulation and immune cell activation, and even low-level activation repeated chronically over years may lead to undesired effects. During hemodialysis, the adsorption of plasma proteins to the dialyzer membrane leads to a formation of a secondary membrane, which can compromise both the uremic toxin removal and hemocompatibility of the dialyzer. Hydrophilic modifications of novel dialysis membranes have been shown to reduce protein adsorption, leading to better hemocompatibility profile and performance stability during dialysis treatments. This review article focuses on the importance of performance and hemocompatibility of dialysis membranes for the treatment of dialysis patients and summarizes recent studies on the impact of protein adsorption and hydrophilic modifications of membranes on these two core elements of a dialyzer.

Randomized comparison of three high-flux dialyzers during high-volume online hemodiafiltration-the comPERFORM study.

Background: Dialyzers should be designed to efficiently eliminate uraemic toxins during dialysis treatment, given that the accumulation of small and middle molecular weight uraemic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for performance during online hemodiafiltration (HDF) in a clinical setting. Methods: comPERFORM was a prospective, open, controlled, multicentric, interventional, crossover study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600 (Fresenius Medical Care Deutschland), xevonta Hi 15 (B. Braun) and ELISIO 150H (Nipro) each for 1 week. The primary outcome was ß2-m removal rate (ß2-m RR) during online HDF. Secondary endpoints were RR and/or clearance of ß2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 versus comparators were tested. Results: Fifty-two patients were included and analysed. FX CorAL 600 showed the highest ß2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its comparators was statistically significant (P = 0.0216 and P < 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 minutes and its sieving properties changed less over time than with comparators. Conclusions: FX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in ß2-m RR. Albumin sieving kinetics point to reduced formation of a secondary membrane.

Polyvinylpyrrolidone in hemodialysis membranes: Impact on platelet loss during hemodialysis.

INTRODUCTION: Hydrophilic modification with polyvinylpyrrolidone (PVP) increases the biocompatibility profile of synthetic dialysis membranes. However, PVP may be eluted into the patient's blood, which has been discussed as a possible cause for adverse reactions rarely occurring with synthetic membranes. We investigated the content of PVP and its elution from the blood-side surface from commercially available dialyzers, including the novel FX CorAL, with PVP-enriched and α-tocopherol-stabilized membrane, and link the results to the level of platelet loss during dialysis as a maker of biocompatibility. METHODS: Six synthetic, PVP containing, dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO [Nipro]; xevonta [B. Braun]) were investigated in the present study. The content of PVP on blood-side surface was determined with X-ray photoelectron spectroscopy (XPS). The amount of elutable PVP was measured photometrically after 5 h recirculation. The level of platelet loss was evaluated in an ex vivo recirculation model with human blood. FINDINGS: Highest PVP content on the blood-side surface was found for the polysulfone-based FX CorAL (26.3%), while the polyethersulfone-based THERANOVA (15.6%) had the lowest PVP content. Elution of PVP was highest for the autoclave steam-sterilized THERANOVA (9.1 mg/1.6 m2 dialyzer) and Polyflux (9.0 mg/1.6 m2 dialyzer), while the lowest PVP elution was found for the INLINE steam sterilized FX CorAL and FX CorDiax (<0.5 mg/1.6 m2 dialyzer, for both). Highest platelet loss was found for xevonta (+164.4% compared to the reference) and the lowest for the FX CorAL (-225.2%) among the polysulfone-based dialyzers; among the polyethersulfone-based dialyzers, THERANOVA (+95.5%) had the highest and ELISIO (-52.1%) the lowest platelet loss. DISCUSSION: Polyvinylpyrrolidone content and elution differ between commercially available dialyzers and were found to be linked to the membrane material and sterilization method. The amount of non-eluted PVP on the blood-side surface may be an important determinant for the biocompatibility of dialyzers.

Computer designed and milled porcelain esthetic resin-bonded fixed partial denture.

A promising method of fabricating porcelain esthetic resin-bonded pontics is proposed. CAD-CAM crown software in the CEREC system is edited and modified to mill the replacement for a missing lower incisor out of a block of porcelain.

The mechanically enhanced phase separation of sprayed polyurethane scaffolds and their effect on the alignment of fibroblasts.

This paper reports a method to fabricate anisotropic scaffolds of tunable porosity and mechanical properties. Scaffolds were fabricated using a computer controlled sprayed phase separation technique. Following fabrication, the sheets were elongated 0, 35 or 70% of their original length to induce varying degrees of scaffold alignment and anisotropy. The nonsolvent used in the phase separation was shown to affect porosity and the elastic modulus. Mouse embryo NIH-3T3 fibroblasts were cultured on the scaffolds to investigate cell response to the anisotropy of the scaffold. A 2D FFT method was used to quantify cellular alignment. Cells were shown to align themselves with the scaffold. This sheet-like scaffold material can be used in single plys or can be laminated to form porous 3D composite scaffolds.

Design and characterization of a modified T-flask bioreactor for continuous monitoring of engineered tissue stiffness.

Controlling environmental conditions, such as mechanical stimuli, is critical for directing cells into functional tissue. This study reports on the development of a bioreactor capable of controlling the mechanical environment and continuously measuring force-displacement in engineered tissue. The bioreactor was built from off the shelf components, modified off the shelf components, and easily reproducible custom built parts to facilitate ease of setup, reproducibility and experimental flexibility. A T-flask was modified to allow for four tissue samples, mechanical actuation via a LabView controlled stepper motor and transduction of force from inside the T-flask to an external sensor. In vitro bench top testing with instrumentation springs and tissue culture experiments were performed to validate system performance. Force sensors were highly linear (R(2) > 0.998) and able to maintain force readings for extended periods of time. Tissue culture experiments involved cyclic loading of polyurethane scaffolds seeded with and without (control) human foreskin fibroblasts for 8 h/day for 14 days. After supplementation with TGF-beta, tissue constructs showed an increase in stiffness between consecutive days and from the acellular controls. These experiments confirmed the ability of the bioreactor to distinguish experimental groups and monitor tissue stiffness during tissue development.