Since Thomas Graham discovered the principle of diffusion in 1854 and Dow Chemical began mass production of hollow fiber blood purification membranes in 1968, blood purification technology has made great progress to date. Among them, the progress of blood purification membranes is notable, especially the progress involving industrial chemistry such as polymer synthesis and hollow fiber membrane production technology has been evolved into a major medical device industry. Furthermore, evaluation methods such as microscopic observation techniques were established, and in parallel, membrane permeation theory based on theoretical and quantitative approaches evolved. Such membrane science and practical application technologies are preceded by USA, Germany and Japan, but recently by China, India and the Middle East countries have been caught up. The innovation of blood purification membranes was the advent of hollow fiber membranes and polysulfone membranes. This review paper describes the advent of blood purification membranes and their subsequent evolution. I would like to evaluate the latest technology of the blood purification membrane from two viewpoints of biocompatibility and membrane permeation theory, and also to touch on future sustainable and disruptive innovation.

The continuous blood purification device used in the intensive care area has achieved remarkable development in safety and operation. However, we have not yet eradicated the medical incidents associated with these devices. In order to prevent such medical accidents, it is important not only to create an environment where medical institutions and manufacturing and retailers cooperate, but it is also important to establish a system for daily inspection so that the original performance of the device can be maintained. This article focuses on the man-machine interface between the operator and the device in the history of blood purification device development in the intensive care area and reevaluates the operability and safety from an ergonomic point of view. And we also present future-oriented functions and prospects required for blood purification devices in next generation.

Devices used for continuous renal replacement therapy (CRRT) are required to (1) be usable for a long time, (2) have superior bio (blood) compatibility, and (3) have superior permeability performance and water removal performance. Excelflo has sharp molecular weight fractionation characteristics and high water permeability performance through giving a gradient structure to polysulfone hollow fiber that has superior biocompatibility. In addition, compared with a dialyzer, hollow fibers with a large inside diameter are placed in a low length over diameter (L/D) ratio container to keep down pressure loss and reduce the stimulation of blood cells. Furthermore, in order to realize long-term treatment, we have made improvements such as suppression of blood retention in the header structure and urethane surface as a CRRT-dedicated treatment device. In this paper, we introduce the design concept and features with physical characteristics, etc., and report on the optimal CRRT filter considered by us.

In the present study, we identified the predictive biomarkers of circuit coagulation in continuous blood purification therapy, and evaluated the efficacy of our circuit coagulation predictive method during continuous blood purification therapy. Twenty-seven samples were obtained from the patients underwent AN69ST-CHDF for sepsis or septic DIC were examined during the period from April 2017 to January 2018. We divided into two groups (coagulated and non-coagulated groups) depending on the circuit coagulation within twenty-four hours from continuous blood purification therapy started. Significant differences were found in thrombin-antithrombin complex (TAT), prothrombin fragment 1＋2 (F1＋2), and AKIN classification between the two groups. Our findings suggest that TAT and F1＋2 are able to predict the process of circuit coagulation during continuous blood purification therapy.

We retrospectively investigated the vancomycin (VCM) prescription, estimated from the pre-calculated clear space ratio of our ICU patients under a sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA). Patients with sepsis who received 1.0 g of vancomycin every 6 hours were analyzed. Median blood concentrations of VCM at 0 hours, 6 hours, and 12 hours were 20.5μg/mL (13.9-22.6) , 18.4μg/mL (17.1-22.3), and 19.7μg/mL (16.4-21.4), respectively. Patients with maintained renal function or dialysis dependency were included in the analysis as it was suggested that estimated VCM prescription during SHEDD-fA could maintain blood concentration at a constant dose regardLess of patients’own residual renal function. This result also applies to the case of hemodiafiltration (HDF) or sustained low-efficiency daily diafiltration (SLEDD) with blood purification equivalent to that of SHEDD-fA.

The present study aimed to investigate the ability of HEpatic failure, LactatE, NorepInephrine, medical Condition, and Creatinine (HELENICC) score to predict long-term mortality. The association of Sequential Organ Failure Assessment (SOFA), SOFA for each organ, and HELENICC scores with 28- and 90-day mortality rates of 94 patients with continuous blood purification (CBP) treatment was investigated. Liver failure, coagulation failure, and circulatory failure were associated with 28-day mortality；coagulation failure and circulatory failure were associated with 90-day mortality. Receiver operating characteristic curve analysis found that both scores had a moderate ability to predict mortality, with no significant difference in the areas under the curve. Liver failure, coagulation failure, and circulatory failure had a poor prognosis in patients with CBP; the HELENICC score may be predictive of long-term mortality.

Aim：The relationship between recombinant thrombomodulin (rTM) and the membrane- and blood circuit-related problems of disseminated intravascular coagulation (DIC) patients who received continuous hemodiafiltration using an AN69ST membrane was examined. Methods: Forty-two patients with an acute-stage DIC score ≥4 points and using nafamostat mesilate were divided into an “rTM-administration group” and “non-rTM-administration group”. Then, we investigated the prevalence of: (i) membrane- and blood circuit-related problems; (ii) achievement of the target treatment time. We also investigated the lifetime of the AN69ST membrane. Results: In the rTM-administration group, the prevalence of membrane circuit-related problems was significantly lower, and achievement of the target treatment time was significantly higher, than that of the non-rTM-administration group. Conclusion: Use of rTM as treatment for DIC may be effective for avoiding membrane- and blood circuit-related problems.

Hemofilters (polymethylmethacrylate, AN-69ST) used for continuous blood purification therapy against septic shock exhibit high adsorption ability of cytokines due to their negative charges. However, this high adsorption ability, often results in filter clotting with platelets, which severely restricts their long-term treatments. In the study, we explored anti thrombotic materials for more useful hemofilters. The phospholipid structure of 2-methacryloxethyl phosphorylcholine (MPC) is similar to that of the vascular endothelium and a co-polymerized with acrylonitrile (AN) to prepare a polyacrylonitrile (PAN)-MPC polymer. The obtained PAN-MPC polymer was coated on a commercial PAN (AN 69) film. The coated PAN membrane was immersed in rabbit whole blood for 24 h and subsequently analyzed for antithrombotic activity using a scanning electron microscope. The results clearly showed a high antithrombotic activity of the PAN-MPC coated PAN membrane.

AN69ST membrane hemofilters have a high adsorption ability for cytokines, but concerns exist regarding their adsorption and removal abilities for antibiotics to use for treatment. Therefore, we examined the effect of the adsorption of meropenem (MEPM), pazufloxacin (PZFX), cefozopran (CZOP), vancomycin (VCM), and teicoplanin (TEIC) onto AN69ST membranes via in vitro experiments. The adsorption ability was evaluated by measuring the absorbance of each antibiotic solution added to the AN69ST membranes over time. We observed that the content rates of TEIC, PZFX, and VCM decreased compared with those of the solution that was not added to the AN69ST membranes；however, the content rates of MEPM and CZOP showed no decrease. Therefore, our results suggest that TEIC, PZFX, and VCM were adsorbed and removed by the AN69ST membranes. Thus, while using AN69ST membranes, it is crucial to set the antibiotic dose for administration by considering the decrease in the blood level.

Blood purification is based on the principles of dialysis, filtration, and adsorption. The molecular weight of myoglobin (Mgb) is 17800 Da, making it a medium-sized molecular compound ; thus, it cannot be separated using the principles of dialysis. With a focus on the principles of filtration, methods using a high cut-off membrane have been developed for Mgb removal; however, albumin loss is a problem with this method. The principle of adsorption is based on the interaction between the membrane material and solute ; thus, if the membrane adsorption characteristics match Mgb, Mgb removal may be possible with this method. However, no study has focused on the principle of adsorption for Mgb removal. In this study, we performed continuous hemofiltration using an AN69ST membrane (AN-CHF) and sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) with a polymethylmethacrylate (PMMA) membrane for a patient with high blood Mgb levels and calculated the Mgb clearance. The Mgb level was 197328ng/ml, indicating a marked increase. AN-CHF (QB: 150ml/min, QF: 1000ml/h) was started, and then the method was switched to SHEDD-fA (QB : 150ml/min, QD : 300ml/min, QF : 1250ml/h). The AN-CHF blood clearance was 9.1ml/min, while SHEDD-fA was 37.9 ml/min. The theoretical filtration clearance limit of SHEDD-fA was 20.8ml/min, and the blood clearance of SHEDD-fA is extremely high, even for substances with a sieving coefficient of 1.0. The involvement of the principle of adsorption was considered in view of the molecular weight of Mgb.

In neonatal hyperammonemia, it is necessary to rapidly lower the blood ammonia level. Although acute blood purification therapy is an effective tool, it is difficult to ensure sufficient blood flow in neonates, and the optimal conditions are unknown. According to the principle of blood purification, in order to obtain sufficient clearance, it is necessary to secure a sufficient blood flow rate (Qb) and a dialysate flow rate (Qd) that is twice or more than the Qb. For two neonates who had hyperammonemia due to inborn errors of metabolism, we were able to perform continuous hemodialysis (CHD) safely with gradually increasing efficiency, while maintaining the ratio of Qb to Qd (Qb：Qd＝1：2). The efficiency in reducing the blood ammonia level was increased with a Qb of 3.57 mL/kg/min and Qd of 1200 mL/h (7.14 mL/kg/h) in case 1 and a Qb of 4.55 mL/kg/min and Qd of 1800 mL/h (9.09 mL/kg/min) in case 2. For neonatal hyperammonemia, a CHD that secures a Qb of at least 3.5 mL/kg/min or more and Qd that is double its Qb may be effective in lowering the blood ammonia level.

Endotoxin adsorption therapy is used to treat severe sepsis. In recent years, adsorption columns have been developed to treat neonatal sepsis, of which polymyxin B-immobilized fiber (PMX) columns can even be used for low-birth-weight neonates. The infant was born at 36 weeks gestation, weighing 2504 g. Within 4 hours after birth, respiratory insufficiency due to Group B Streptococcus infection was observed. Blood pressure was stabilized after antibiotic and nitric oxide (NO) treatments; however, procalcitonin concentrations were high and symptoms of sepsis were observed. Blood purification therapy including PMX, was administered on the third day after birth. Improvement in respiration and circulation was observed after the introduction of blood purification therapy. As a result, the administration of NO and catecholamine preparations was gradually reduced, and blood purification therapy was discontinued after 53 hours. The infant was discharged about 2 months later. The development of low-dose PMX-01R has made it possible to implement the safe treatment of sepsis in newborns.

A reverse osmosis (RO) water circulation unit was developed to decrease endotoxin (ET) activity and viable bacteria count in an individual dialysis system. The system along with the RO unit was introduced to a ward with four beds for severe patients, where the equipment necessary for an intensive care unit (ICU) was available (i.e., a functional ICU). This system, which chiefly comprises an RO tank and a circulation pump, receives RO feed water from an individual RO unit and supplies RO water to the loop pipe. In the present study, we determined ET activity and viable bacterial count in RO water in the circulation line of the system. Samples were collected from the water feed line, water supply line, and RO tank. We found that ET activity and viable bacteria count were maintained at ＜0.0001 EU/mL (which is below the measurement sensitivity) and 0–0.03 CFU/mL, respectively. Therefore, we consider that this RO water circulation unit is beneficial for use with an individual dialysis system because it facilitates a stable supply of high quality RO water.