Novel substitution technique in intermittent infusion hemodiafiltration (I-HDF) therapy using back filtration as substitution.

An infusion of dialysate into the blood compartment across the membrane using back filtration in dialysis therapy provides a stabilizing blood pressure and a membrane flushing during treatment. We devised a method to flush the membrane effectively and tried to find the optimum infusion patterns for intermittent infusion hemodiafiltration (I-HDF) from the aspect of solute removal by computing the pressure distribution in a diafilter. Bovine blood experiments were performed under following three modes: control HD in which no intentional filtration was involved, and two I-HDF in which back filtration was made either under counter current or under parallel flow. The inner surface of the hollow fiber before and after the experiment was observed using FE-SEM. According to the computation of the pressure distribution, a large amount of normal filtration occurs near the blood inlet in control HD. In addition, when the back filtration is performed under parallel flow, the amount of backfiltration near the blood inlet is 3.43 times higher than that in the case of counter current. Clearance (CL) of inulin remained at the highest level when the back filtration was performed under parallel flow. Near the blood inlet where the fouling was significantly formed, many macropores remained on the membrane when the backfiltration was performed under parallel flow. The degree of fouling showed a distribution along with the blood flow and the pressure distribution. Furthermore, the more effective recovery of CL can be expected by introducing the backfiltration under parallel flow to which fouling was significantly formed.

Replication of fouling in vitro in hollow fiber dialyzers by albumin immobilization.

For designing and evaluating the dialyzer and investigating the optimal therapeutic conditions, in vitro studies bring us many useful findings. In hemodialysis, however, the membrane fouling due to protein molecules reduces solute removal performance. Therefore, we investigated a method for replicating the fouling in dialyzers in aqueous experiments. After the albumin solution was circulated in the test circuit with a dialyzer, a glutaraldehyde solution was pumped into the dialyzer to immobilize albumin on the hollow fiber membrane. Under various immobilization conditions, the permeability of creatinine and vitamin B12 was evaluated by dialysis experiments. The creatinine clearance after immobilization of albumin was decreased, suggesting pore plugging by our fouling replication method. The glutaraldehyde crosslinked albumin molecules that adhered them to the membrane firmly. Moreover, the degree of fouling may be controlled by changing the concentration of albumin solution and the volume of glutaraldehyde solution used for immobilization. Our fouling replication method was applied to three types of polyester polymer alloy (PEPA) dialyzers and one polysulfone (PSf) dialyzer. This method enables to evaluate the permeability of various dialyzers with fouling in vitro that will be of great help in collecting data for designing dialyzers.

Effect of Membrane Surface Area on Solute Removal Performance of Dialyzers with Fouling.

In a clinical situation, since membrane fouling often causes the reduction of solute removal performance of the dialyzer, it is necessary to evaluate the performance of the dialyzer, considering the effects of fouling even in aqueous in vitro experiments that are useful for the better design of dialyzers. We replicated the membrane fouling by immobilizing albumin on the membrane in a dialyzer using glutaraldehyde as a stabilizer. The modules of various membrane surface areas with and without replication of the fouling were used for performance evaluation of solute (creatinine, vitamin B12, and inulin) removal in dialysis experiments in vitro. Clearances for these solutes in the modules with fouling were lower than those without fouling. Furthermore, the smaller the surface area, the larger the fouling effect was observed in all solutes. Calculated pressure distribution in a module by using a mathematical model showed that the solute removal performance might be greatly affected by the rate of internal filtration that enhances the solute removal, especially for larger solutes. The increase in the rate of internal filtration should contribute to improving the solute removal performance of the dialyzer, with a higher effect in modules with a larger membrane surface area.