The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

Elobixibat alleviates chronic constipation in hemodialysis patients: a questionnaire-based study.

BACKGROUND: Hemodialysis patients are prone to constipation, which can adversely affect their quality of life (QOL). Elobixibat, a highly selective inhibitor of the ileal bile acid transporter, can increase the bile acid level in the colon and, subsequently, enhance colonic motility and secretion. In hemodialysis patients with chronic constipation, it may have a novel action mechanism. However, the effect of elobixibat on such patients' QOL had not been reported. This study aimed to evaluate the effect of elobixibat on the QOL of hemodialysis patients with chronic constipation. METHODS: This was a multicenter, observational study that used the Japanese version of the Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaire on 27 patients (18 men and nine women, age range 47-90 years), who satisfied the Rome 3 diagnostic criteria for functional constipation and were already taking other drugs for constipation. These patients were administered elobixibat 10 mg/day and were asked to respond to the PAC-QOL questionnaire at baseline and after 4 weeks. Bayesian statistics were used to confirm our results. RESULTS: The number of spontaneous bowel movements per week increased significantly from 2.6 ± 1.2 to 4.1 ± 2.1 (p < 0.001), and the Bristol Stool Form Scale score significantly improved from 1.9 ± 0.8 to 3.6 ± 0.7 (p < 0.001). The Cronbach's alpha was 0.95, and the Guttman split-half reliability coefficient was 0.90. There were significant decreases in the physical discomfort scores from 1.94 ± 0.79 to 0.97 ± 0.72 (p < 0.001); psychosocial discomfort from 1.16 ± 0.93 to 0.63 ± 0.58 (p < 0.001); worries/ concerns from 1.84 ± 0.73 to 1.27 ± 0.59 (p < 0.001), and satisfaction from 2.79 ± 0.61 to 1.98 ± 0.77 (p < 0.001). The total PAC-QOL score significantly decreased from 1.83 ± 0.79 to 1.17 ± 0.56 (p < 0.001). Bayesian statistics confirmed the results' significance. CONCLUSIONS: Elobixibat reduced the PAC-QOL scores for hemodialysis patients with chronic constipation and improved the patients' QOL. It may serve as a new option for treating constipation in hemodialysis patients.

In vitro Evaluation of Solute Removal Characteristics in Intermittent Infusion Hemodiafiltration.

BACKGROUND: In a typical hemodialysis (HD) session, excessive water removal sometimes induces peripheral circulatory failure and a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF), a new modality of dialysis therapy, has been developed to improve peripheral circulation by repeated intermittent infusion of dialysate during an HD session. In a typical I-HDF session, we infuse a volume of 200 mL of ultrapure dialysate by backfiltration at 150 mL/min every 30 min. The same volume is alternately removed from the patient's blood by filtration at a constant rate after each infusion. However, solute removal characteristics in I-HDF have not been clarified previously. We therefore conducted an in vitro study to investigate the characteristics of solute removal and the factors affecting such removal. SUMMARY: We used human plasma to evaluate the effects of filtration (QF)/infusion (QI) flow rates on solute clearance (CL) and to estimate the time-averaged solute CL (TACL) values. The CL values for all solutes decreased with increasing QI. For small molecules such as urea, the CL values predominantly decreased with increasing QI because of decreasing diffusive transport. For medium and large solutes such as ß2 microglobulin or larger, CL values predominantly increased with increasing QF because of increasing convective transport. However, the effects of these changes on TACL values were small compared with the CL value in a typical HD session because of the alternate filtration and infusion in I-HDF. Key Messages: Solute removal characteristics in I-HDF do not differ significantly from those in conventional HD treatment.

Validity of Intermittent Infusion Hemodiafiltration.

BACKGROUND: Intermittent infusion hemodiafiltration (I-HDF) has been developed to prevent a rapid drop in blood pressure during a dialysis session and to improve peripheral circulation. In Japan, >10,000 dialysis patients underwent treatment with I-HDF in 2017, and the number of dialysis patients is increasing year by year. I-HDF involves the intermittent infusion of ultrapure dialysis fluid or sterile nonpyrogenic substitution fluid, for example, at a volume of 200 mL and a rate of 150 mL/min by backfiltration every 30 min during treatment. The total infusion volume can therefore be estimated at 200 (mL) × 7 (infusions) or 1.4 L/session. I-HDF may be regarded as online HDF with a very small replacement volume. SUMMARY: Several clinical trials of I-HDF have been conducted in Japan. (1) In a 2007 study, despite there being no differences noted in the volume of water removal between hemodialysis (HD) and I-HDF, a significantly lower rate of reduction in the time-averaged blood volume was seen in I-HDF than in HD, so the plasma refilling rate was greater during I-HDF. (2) In a 2015 study, at 13 weeks after a switch from HD, I-HDF was found to be significantly superior to HD in terms of the incidence of events needing intervention by medical staff. However, significantly lower blood ß2-microglobulin (MG) and α1-MG levels were observed in the predilution online HDF (pre-HDF) group than in the I-HDF group, and the amount of albumin leak was lower in the I-HDF group than in the pre-HDF group. (3) In a 2017 study, compared with HD, I-HDF was associated with a reduced number of interventions for intradialytic hypotension and less severe tachycardia, suggesting less sympathetic stimulation during I-HDF. Key messages: I-HDF is a valid treatment option because it is associated with an increased plasma refilling rate and fewer interventions needed by medical staff.

Relationship between Dose of Bolus Dialysate Infusion and Blood Pressure in Intermittent Infusion Hemodiafiltration.

BACKGROUND: Intermittent infusion hemodiafiltration is a recently developed convective method of renal replacement therapy using cyclic back-filtration infusion. Quick and regular infusion prevents intradialytic hypotension. However, the optimal dose of bolus dialysate infusion required to stabilize blood pressure has not been reported. Here, we investigated the relationship between the dose of bolus dialysate infusion and blood pressure. SUMMARY: A total of 77 patients on maintenance hemodialysis were enrolled in this study. Dialysate was infused rapidly by backward filtration at a rate of 150 mL/min at 30-min intervals using an automated dialysis machine. The effects with two bolus infusion volumes (100 and 200 mL) were compared, each for an observation period of 2 weeks. Systolic blood pressure (SBP) was measured at the start and at the end of each dialysis session, and the highest SBP and lowest SBP measurements were also recorded. Patients were divided according to dry weight into a <52 kg group and a ≥52 kg group, and various parameters were compared between the 100 and 200 mL bolus infusion volumes in each group. Among patients in the <52 kg group, SBP did not vary at any of the time points. However, for patients in the ≥52 kg group, SBP at the end of treatment was significantly lower in the 100-mL group than in the 200-mL group (141 ± 20 vs. 144 ± 21 mm Hg, p = 0.041), and the minimum SBP was also lower in the 100-mL group than in the 200-mL group (127 ± 17 vs. 131 ± 18 mm Hg, p = 0.010). Key Messages: Among patients with a dry weight of ≥52 kg, blood pressure was more stable when a bolus fluid volume of 200 mL was used, compared with a volume of 100 mL. However, for patients with a dry weight of <52 kg, the significance of the difference in bolus fluid volumes disappeared. Thus, the replacement fluid volume might be better determined based on the patient's dry weight. TRIAL REGISTRATION: UMIN 000028145, Registered July 10, 2017.

A Clinical Significance of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared to Hemodialysis: A Multicenter Randomized Controlled Crossover Trial.

BACKGROUND: Intermittent infusion hemodiafiltration -(I-HDF) using repeated infusion of ultrapure dialysis fluid through a dialysis membrane or sterile nonpyrogenic substitution fluid was developed to prevent a rapid decrease in blood pressure by increasing the patient's circulating blood volume, to enhance the plasma refilling rate by improving peripheral circulation, and to enhance solute transfer from the extravascular space to the intravascular space by enhancing the plasma refilling rate. Furthermore, the effect of fouling caused by attachment of proteins to the membrane as a result of ultrafiltration can be reduced by backflushing of the membrane with the purified dialysate in I-HDF. Although there have been several clinical trials of I-HDF, there have been no comparisons of the clinical significance of and indications for -I-HDF with those of conventional hemodialysis (HD). OBJECTIVE: The aim of this multicenter randomized controlled crossover trial was to compare the clinical significance of -I-HDF with that of HD in Japan. METHOD: Patients were randomized to receive HD, I-HDF, and HD (group A) or I-HDF, HD, and I-HDF (group B) in that order for 14 weeks each. The sample size of 70 was determined based on the operability and patient availability. Treatment outcomes were evaluated 5 and 14 weeks after the start of each treatment period. The patients received 4-h treatment sessions with no changes in session duration or anticoagulant therapy during the study. I-HDF was performed using a GC-110N dialysis machine. Two hundred milliliters of ultrapure dialysis fluid were infused at a rate of 150 mL/min by backfiltration every 30 min during treatment. The first and last infusions were performed 30 min after the start and 30 min before the end of treatment, respectively. The total estimated infusion volume per session was 1.4 L (i.e., 200 mL × 7 infusions). I-HDF is a type of online HDF with a small fluid replacement volume. An ABH-P polysulfone membrane hemodiafilter was used for -I-HDF and a class 1 or 2 hemodialyzer with a polysulfone membrane not coated with vitamin E and approved by the Japanese reimbursement system was used for HD. The primary outcomes were the Short Form-36 version 2 summary scores for quality of life and the visual analog scale scores for clinical symptoms. Secondary outcomes were vital signs, number of interventions, and pre-treatment blood test results. These variables were evaluated 1 week before at the start of the study, and at 5 and 14 weeks after the start of each treatment period. The removal characteristics of the various solutes were evaluated when possible on the first day of each treatment period. All patients provided written informed consent to participate. RESULTS: Thirty-two patients in group A and 32 patients in group B completed the trial. There were no differences in the primary or secondary outcomes between I-HDF and HD. Serum α1-microglobulin (MG) levels at 14 weeks were significantly lower for I-HDF than for HD. During treatment, the removal rates for urea and creatinine, which are low molecular weight substances, were significantly lower during I-HDF than during HD. In contrast, the ß2-MG and α1-MG removal rates were significantly higher during I-HDF than during HD. Furthermore, there was significantly less albumin leak during I-HDF than during HD. The solute removal results reflect the difference in pore size between the hemodiafilter used for I-HDF and the hemodialyzer used for HD and the difference in convective transport attributable to filtration between the 2 methods. CONCLUSIONS: These findings show that the removal rates of low molecular weight substances are significantly lower and those of medium to high molecular weight substances are significantly higher with I-HDF than with HD. They also indicate that there is significantly less albumin leak during I-HDF than during HD, meaning that I-HDF may be a particularly suitable dialysis modality for patients with malnutrition and the elderly in Japan.

Carnitine Profile by Tandem Mass Spectrometry and Dialysis Patients.

BACKGROUND: Carnitine deficiency is a common condition in hemodialysis patients. Therefore, abnormalities in fatty acid metabolism and organic acid metabolism are also common in dialysis patients. Tandem mass spectrometry is a standard technique in pediatric and neonatal medicine. However, it could be a new powerful tool in other fields for estimating the state of intracellular fatty acid metabolism. SUMMARY: Tandem mass spectrometry has recently revealed the relationships between carnitine profile and dialysis patients' anemia, reduced physical function, and survival rate. Fatty acid and organic acid metabolism, which could previously only be evaluated qualitatively, can now be quantitatively assessed. Key Message: The applications of tandem mass spectrometry are expected to expand not only in the field of dialysis but also in clinical medicine in general.

Association between 4-year all-cause mortality and carnitine profile in maintenance hemodialysis patients.

BACKGROUND: Patients on dialysis are in a chronic carnitine-deficient state. This condition may be associated with abnormalities of the fatty acid and organic acid metabolisms. Carnitine is required for ß-oxidation of the long-chain fatty acids; therefore, carnitine deficiency decreases the efficiency of ATP synthesis and may incur death. However, the details of this association remain unknown. We examined the relationship between ß-oxidation efficiency represented by the carnitine profile and 4-year all-cause mortality in hemodialysis patients. METHODS: The carnitine profiles of 122 hemodialysis patients were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The associations between the 4-year all-cause mortality and carnitine profile as well as the clinical backgrounds of the patients were investigated. A survival analysis was conducted by the Kaplan-Meier survival method and multivariable Cox proportional hazard analysis. The bootstrap method was performed to confirm the stability and robustness of our model. RESULTS: Of the 122 subjects analyzed, 111 were selected and 24 died during the observation period. Stepwise multivariable Cox regression demonstrated that diabetes state [Hazard ratio (95% confidence interval), 4.981 (2.107-11.77)], age [HR (95% CI), 1.052 (1.014-1.091)], and the acetylcarnitine/(palmitoylcarnitine+octadecenoylcarnitine) [C2/(C16+C18:1)] ratio [HR (95% CI), 0.937 (0.904-0.971)] were independent significant factors of 4-year all-cause mortality. The bootstrap method confirmed the significance of these three factors. CONCLUSION: The 4-year all-cause mortality negatively correlated with the C2/(C16+C18:1) ratio. Improvement of the impaired ß-oxidation state after L-carnitine administration may ameliorate prognosis.

Ferritin: Diversity and Management of Ferritin Measurement Methods.

BACKGROUND: Serum ferritin is one of the most important and widely used markers of iron metabolism, and is a recommended standard index of iron dynamics in guidelines for renal anemia in many countries. However, serum ferritin measurement has several disadvantages. For example, it is prone to being influenced by underlying disease, and there is considerable systematic bias among different methods of measurement. SUMMARY: Systematic bias affects not only the measurement results, but also the therapeutic strategy to be used in accordance with the relevant guidelines, and consequently the cost of medical treatment. Key Messages: Manufacturers should reduce variability in their serum ferritin assay kits. Researchers should take into account propagation of error in the analysis of measurement values, and clinicians should evaluate laboratory data with care.

Intermittent Infusion Hemodiafiltration: The Principle and Its Clinical Application.

The present study aimed to propose a new hemodiafiltration (HDF) method (intermittent infusion HDF) that repeats intermittent infusion during hemodialysis to temporarily enhance peripheral circulation and improves solute removal efficiency through (a) correcting blood distribution (increase in effective vascular surface area), (b) stirring body fluids, and (c) promoting solute removal and examining its clinical effects.

Intensive Hemodialysis: Effects of Treatment Time and Frequency on Time-Averaged Concentrations of Solutes.

Most of chronic renal disease patients receive 4-h hemodialysis (HD) sessions thrice a week. This is the minimum therapy needed to maintain life. This conventional HD therapy protocol is, however, inadequate to prevent dialysis-related complications. On the other hand, some intensive HD therapies, such as "short daily dialysis," "quotidian dialysis," etc., are being adopted in some dialysis institutions for maximizing the beneficial effects of HD on the quality of life/activities of daily living of the patients. In this paper, the effects of dialysis treatment time and frequency on the adequacy of solute removal in these intensive HD therapies protocols were examined by kinetic modeling using a 1-compartment model. In this model, it is presupposed that urea is distributed throughout the total body fluid compartment and ß2-microglobulin (ß2-MG) is distributed throughout the extracellular compartment. The time-averaged concentrations (TACs) of BUN and ß2-MG can be estimated by inputting the body weight, generation rate of the solute, dialyzer clearance for the solute, and the dialysis treatment time and frequency into the model. According to the results, the TACs were strongly dependent on the total dialysis time per week (T) value and to a slightly lesser degree on the dialysis frequency per week (N) value for both solutes. It is concluded that the 1-compartment model introduced in this study is valid for estimating the TACs of BUN and ß2-MG in patients undergoing maintenance HD therapy, and T and N values are important factors influencing the adequacy of solute removal in patients receiving maintenance HD therapy.

Association between resistance to erythropoiesis-stimulating agents and carnitine profile in patients on maintenance haemodialysis.

OBJECTIVE: Patients on dialysis are in a chronic carnitine-deficient state. This condition may be associated with abnormalities in fatty acid and organic acid metabolism; however, the details are unknown. We investigated the association between carnitine profiles before and after dialysis and the erythropoiesis-stimulating agent (ESA) resistance index (ERI), which is a significant prognostic factor in patients on maintenance haemodialysis. METHODS: This was a cross-sectional study. We measured the carnitine profile of 79 patients on maintenance haemodialysis before and after dialysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The associations between the ERI and pre-dialysis carnitine profile, removal rate of various carnitines, and previously-reported ERI-related factors were investigated. Significant factors were determined with stepwise multiple regression analysis and validated with the bootstrap method. SPSS version 22.0 was used for analysis, and P < 0.05 was considered statistically significant. RESULTS: The removal rate of long-chain acylcarnitine with dialysis was lower than that of short-chain or medium-chain acylcarnitines. Stepwise multiple regression analysis (n = 79) demonstrated that 3-hydroxy isovalerylcarnitine (C5-OH, P < 0.001, ß = -0.469) and stearoylcarnitine (C18, P < 0.001, ß = 0.390) were independent significant factors (R2 = 0.239) of ERI. The bootstrap method similarly indicated these two to be significant factors. CONCLUSION: ERI positively correlated with long-chain C18 acylcarnitine and negatively correlated with short-chain C5-OH acylcarnitine. C5-OH and C18 acylcarnitines at baseline might be contributing factors in distinguishing responders from nonresponders after L-carnitine administration.

Double filtration plasmapheresis: Determination of the optimal albumin concentration in the supplementation fluid.

Many kinds of technologies have been introduced and successfully developed for therapeutic apheresis. During the DFPP treatments, the patient's blood volume (BV) often decreases with time due to albumin loss induced by inadequate albumin infusion in a supplementation fluid. We examined the change of BV by a continuous hematocrit (HCT) monitor, CRIT-LINE™, during an in vivo study for nine patients. As a result, albumin loss was fairly occurred in some DFPP treatments. The decrease of patient's BV was induced by an oncotic pressure drop due to albumin loss and often resulted in a blood pressure drop. This is a serious problem for DFPP. We should avoid the patient is suffering from these adverse effects. In order to determine the optimal concentration CS and volume VS values of a supplemented albumin solution, we introduced a variable blood volume model for albumin transport in DFPP.

Clinical Effectiveness of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared with Predilution On-Line Hemodiafiltration.

BACKGROUND: In conventional hemodialysis (HD) treatment, excessive water removal sometimes induces a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF) has been developed to improve patients' peripheral circulation by repeated intermittent infusion during HD treatment. SUMMARY: A prospective, multicenter, parallel group comparative trial examined the clinical effectiveness of I-HDF compared with predilution on-line HDF (pre-HDF), the most popular on-line HDF therapy in Japan. Patients were allocated to 2 groups after matching for age (± 5 years), dry weight (± 5 kg), and presence/absence of diabetes. After informed consent was obtained, 36 patients (18 pairs) participated in the trial. The results showed no difference in clinical condition or quality of life (QOL) scores between the 2 therapy groups. The rate of reduction in systolic blood pressure initially showed no difference between the groups, but decreased slightly as the trial proceeded after changing from HD therapy. There was also no difference in the incidence rate of treatments initially, although this significantly decreased in both groups as the trial proceeded. Rates of ß2-microglobulin removal were significantly higher in the pre-HDF group than in the I-HDF group. At the same time, the amount of albumin leakage during treatment was significantly greater in the pre-HDF group. Key Messages: The clinical condition and QOL of patients receiving I-HDF was not inferior to those receiving pre-HDF. Pre-HDF demonstrated a significantly higher removal rate of middle- and larger-molecular-weight solutes and higher albumin leakage compared with I-HDF.

Optimal Design of Dialyzers.

BACKGROUND: Several types of synthetic dialysis membranes, including polysulfone, polyethersulfone, and polyester polymer alloy membranes, have asymmetrical structures. Dialyzers with these membranes show higher water and solute transport performance because the actual membrane thickness, which is related to the water and solute transfer resistance, is quite small compared with that in membranes with a homogeneous structure. SUMMARY: The performance of a dialyzer depends not only on membrane permeability to water and solutes, but also on flow conditions of the blood and dialysate, which are determined during dialyzer fabrication. Many types of high-flux dialyzers with high-performance membranes have a high internal filtration/backfiltration (IF/BF) flow rate. In the enhanced IF/BF dialyzer, membrane fouling occurs more readily than with the conventional dialyzer because of the high local transmembrane pressure needed to enhance the IF/BF flow rate. To select the optimal enhanced IF/BF dialyzer for individual patients, we need to balance the disadvantage of membrane fouling with the advantage of increased convective transport. Key Messages: The following principles should guide dialyzer development in the near term. (1) Dialyzers should show high performance for the removal of low-molecular-weight proteins related to certain complications under conditions of low albumin and amino acid loss. (2) Dialyzers with biocompatible membranes are required to prevent severe adverse reactions, even though the causal relationship between these reactions and some complications remains to be clarified.

Effects of protein leakage on online monitoring of ultraviolet absorbance in spent dialysate.

Recently, dialysis dose during hemodialysis treatment has been monitored by measuring the concentration of urea-like solutes such as uric acid in spent dialysate using near-ultraviolet (UV) light. The measured absorbance has been shown to have a good correlation with the time course of urea level even if the absorbance does not result from urea. However, the spent dialysate includes various solutes such as uric acid and albumin as well as unknown solutes that also absorb UV light. The effects of these solutes on monitored absorbance values are not clear. In this study, we evaluated the effect of protein leakage on data from the UV monitoring of spent dialysate. Albumin leakage in the earlier stage of the treatment may result in an increase in absorbance greater than the expected value. As a result, there is a possibility that the dialysis dose is overestimated. On the other hand, the quantity of albumin leakage could be estimated by a spent dialysate monitoring technique combined with a protein removal process.

[Roles of and Team Medical Care Involving Clinical Engineers in Blood Purification Therapy].

Progress in medical care strongly depends on the development of pharmaceutical and medical technologies. Multi-disciplinary care by a medical team is required for the diversity of medical care. "Clinical engineering technician (CET) " is one of the national medical licenses in Japan. Many CETs are engaged in blood purification therapies. Team medical care, involving medical doctors, nurses, CETs, etc., in the hemodialysis field is useful for the early detection of complications in dialysis patients and provision of appropriate treatments. In some medical facilities, for example, progressive approaches such as appropriate nutritional guidance by a dietitian or exercise therapy by a physical therapist are practiced in advance. Clinical laboratory technologists (CLTs), furthermore, play an important role in team medical care for dial- ysis therapy. They can use ultrasonic equipment for vascular access management. Based on the results of the ABI and SPP measurements by CLTs, medical doctors can diagnose PAD in dialysis patients. [Review].

Performance evaluation of developed polysulfone membrane hemodiafilters, ABH-F and ABH-P, in post- and pre-dilution hemodiafiltration.

ABH-F and ABH-P have been developed for hemodiafiltration (HDF) therapy. In this study, we evaluated the solute removal characteristics of the hemodiafilters in a bovine blood in vitro study. The hemodiafilters were examined for 120 min at various filtration flow rates (Q F) (31.2-250 mL/min) under a constant blood flow rate of 250 mL/min and constant dialysate flow rates of 500/250 mL/min in pre-dilution HDF (pre-HDF) and post-dilution HDF (post-HDF). Creatinine clearance in pre-HDF was approximately 85% of that in post-HDF because it was removed by molecular diffusion dominantly. The initial clearances of ß2-microglobulin and α1-microglobulin increased with Q F and these values slightly and steeply decreased with time due to membrane fouling. Under a same Q F of 62.5 mL/min, higher clearance values in post-HDF were obtained compared with those in pre-HDF. All clearance values of ABH-P were higher than those of ABH-F under the same Q F. It seems that the ABH-P has a larger pore size of membrane than that in ABH-F. The creatinine and α1-microglobulin clearance values were obtained as highest at post-Q F62.5, the ß2-microglobulin clearance values and transmembrane pressure were obtained as highest at pre-Q F250. Large solute clearances such as α1-microglobulin and albumin decreased with time in all HDF experiments. Time decay of large solute clearance values was observed in the HDF modality that had a higher clearance of the solute at 5 min later after the start of experiment.

The past, present and future of the dialyzer.

Several types of dialysis membranes have been developed in the history of hemodialysis therapy. Regenerated cellulose had been widely used for a long time, since the beginning of dialysis therapy. Regenerated cellulose is strongly hydrophilic, which enables lower membrane thickness and miniaturization of the dialyzer. The cellulose triacetate membrane has greater performance because of the lower thickness of the membrane and its lack of swelling due to high hydrophobicity. Many types of synthetic membranes, such as polysulfone, polyethersulfone and polyester polymer alloy membranes, have asymmetrical structures. Dialyzers with these membranes show higher capacities for water and solute transport because the actual membrane thickness, which is related to the water and solute transfer resistance, is quite small compared to that in membranes with homogeneous structures. The development of highly biocompatible membranes will be required in the future so as to prevent the development of adverse reactions and related complications. The performance of a dialyzer depends not only on the membrane permeability but also on the flow conditions of the blood and dialysate. Many types of dialyzers with high-performance membranes have been developed as a result of advances in membrane and device technologies. Recently, many types of high-flux dialyzers with high-performance membranes with a high internal filtration (IF)/backfiltration (BF) flow rate have been introduced. IF-enhanced hemodialysis using an enhanced IF dialyzer seems to be more convenient than hemodiafiltration therapy because it requires no additional equipment, such as a roller pump. In the near future, dialyzers should be developed with high capacities for the removal of low-molecular-weight proteins (LMWPs) related to complications and with low capacities for the loss of albumin and amino acid. Dialyzers with a sharp cut-off membrane between LMWPs and albumin and dialyzers with a special function, i.e., an adsorptive property for some LMWPs, are required. In addition, dialyzers with biocompatible membranes are necessary to prevent severe adverse reactions, although the causal relationship between these reactions and some complications are yet to be clarified.