Hiroshi Tsukao

Evaluation of the Biocompatibility of Dialysis Membranes

Background: Improvements in the biocompatibility of dialysis membranes have reduced biological responses elicited by blood-membrane interactions. In this article, recent technological developments in dialysis membranes with regard to biocompatibility and recent progress in the evaluation of the biocompatibility of dialysis membranes are reviewed. Summary: The focus of investigation into dialysis membranes in recent years has focused on not only membrane materials, but also their surface textures, which have been changed, for example, by coating with vitamin E or by changing the amount and type of hydrophilizing agents used. Research and development is directed at altering the chemical and physical properties of membrane surfaces to suppress biological responses that are particularly elicited as a result of platelet activation. To develop membranes with excellent biocompatibility, biocompatibility should be evaluated on a like-for-like basis under conditions that are similar to those in clinical settings. Evaluation using actual dialyzers can be performed using porcine blood, platelet-rich plasma isolated from porcine blood (and platelet-rich plasma with leukocytes), or suspension of neutrophils isolated from porcine blood or cultured human monocytes. Key Messages: Highly biocompatible dialysis membranes can be developed when the overall correlations among biological reactions are examined by integrating all data on biological responses elicited by blood-membrane interactions or mutual interactions among blood cells.

Activation of platelets upon contact with a vitamin E-coated/non-coated surface

The purpose of this study was to determine the effects of a vitamin E-coated surface on platelet activation, focusing on the interactions among the vitamin E-coated surface, platelets and leukocytes. Platelet-rich plasma (PRP) or PRP containing leukocytes (LPRP) was used. No difference was observed in platelet activation between PRP and LPRP for a vitamin E-coated membrane, meaning that platelet activation triggered by leukocytes was suppressed in plasma coming in contact with a vitamin E-coated membrane, while the membrane itself directly induced platelet activation. The antioxidant capacity of the vitamin E-coated membrane in contact with PRP or LPRP was partially reduced, but sufficient residual capacity remained. The in vitro experiments using an oxidized vitamin E-coated surface revealed that P-selectin expression and superoxide anion production in the platelets and platelet adhesion were induced by contact with the oxidized vitamin E-coated surface. We conclude that contact with a vitamin E-coated surface reduces platelet activation mediated by superoxide anions, probably by reducing superoxide anions, but during the process of the reduction, the vitamin E-coated surface itself becomes oxidized, which again causes platelet activation. The beneficial effects of a vitamin E-coated dialyzer in respect of platelet activation were counteracted by the formation of oxidized vitamin E.

Urea concentrating ability of artificial renal tubule based on countercurrent multiplier system using electrodialysis, dialysis and filtration

Countercurrent multiplier systems have been found in various organs of various animal species. In a mammalian kidney, countercurrent multiplier system plays an important role in the process of urine concentration. An artificial renal tubule which can concentrate urea is one of the key elements to develop a wearable artificial kidney for the patients currently undergoing intermittent hemodialysis therapy. The objective of the present study was to develop a biomimetic artificial renal tubule based on the countercurrent multiplier system. We mimicked active transport of NaCl at ascending limbs of the Henle loop by electrodialysis and mimicked passive transport of the solute and water transport via water channel at descending limbs and collecting ducts by dialysis and filtration. The membranes used for electrodialysis, dialysis and filtration were placed parallel to each other to establish countercurrent configuration. We examined urea concentrating ability of the fabricated prototype module of artificial renal tubule based on the countercurrent multiplier system. The fabricated prototype module was capable of concentrating urea approximately 1.3 fold. These results indicate that the countercurrent multiplier system is useful to develop an artificial renal tubule.

Internal filtration induces severe concentration of blood cells inside hollow-fiber dialysis membrane at the start of postdilution hemodiafiltration

The hydraulic permeability of the dialysis membrane used for hemodiafiltration (HDF) is high, so that a large amount of internal filtration occurred in addition to ultrafiltration required for water removal and fluid replacement. Especially for the period immediately after the start of HDF, severe concentration of blood cells by internal filtration is likely to occur. The aims of this study was, using a mathematical simulation, to evaluate the amount of internal filtration and resulting blood cell concentration inside the hollow fiber and to develop a strategy to avoid the severe hemoconcentration during postdilution HDF. To this end, we calculated maximum internal filtration rate, and maximum hematocrit at varying blood flow rate, dialysate flow rate, and ultrafiltration rate. We found that at the start of the HDF, severe concentration of blood cells can occur where maximum hematocrit reached over 60%, even the dialyzer was designed to ensure minimal internal filtration. The hemoconcentration was not actually severe after membrane fouling occurred. To prevent the initial severe concentration of blood cells during HDF, at the start of the treatment the blood and dialysate flow rate should be below 100 ml/min and no ultrafiltration should be performed.

Evaluation of a newly developed continuous protein separation system based on a difference in the isoelectric points of the proteins

Several advanced glycation end products (AGEs) were identified as potential uremic toxins, which were accumulated in patients with end-stage renal disease. Current blood purification technology, however, can not provide a method for separating AGE-modified proteins from normal proteins. The aim of this study was to develop a continuous protein separation system capable of separating AGE-modified proteins from normal proteins. We focused on the change in the isoelectric point of AGE-modified proteins and evaluated a manufactured prototype device based on a free flow electrophoresis. We use myoglobin (isoelectric point: 7.35) solution as a test solution. Protein concentration and pH were measured at varying flow rates (1.3, 3.4, 7.2 mL/min) and voltages (10 and 50 V).When the voltage = 50 V, pH gradient was formed in the electrophoretic chamber after 15 min and myoglobin concentration increase at the center of the electrophoretic chamber. Myoglobin was focusing on sample outlet where the pH of the solution near the isoelectric point. Concentration ratio (maximum / average) was 1.25 -1.30 and had a maximum value at a flow rate of 3.4 mL/min. This newly developed device for continuous protein separation was capable of concentrating myoglobin at the specific position in the electrophoretic chamber and continuously collecting the concentrated myoglobin. However, the concentration ratio of myoglobin was low. The optimization of the operating condition required to improve the selectivity.