Michio Mineshima

The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age

Most published reports indicate that intensified hemodialysis results in better pregnancy outcomes. Here we studied clinical characteristics and the outcomes of 28 pregnant women receiving hemodialysis. We found an association between maternal blood data and birth weight, and gestational age and outcomes. There were 18 surviving infants who were followed up for one year. In the others there were 4 spontaneous abortions, 1 stillbirth, 3 neonatal deaths and 2 deaths after birth. Analysis of blood chemistry for 20 pregnancies from 12 weeks of gestation until delivery showed that the average hemoglobin level was significantly higher in the group that successfully delivered than in the unsuccessful group. There were significant negative relationships between the blood urea nitrogen (BUN) level and the birth weight or gestational age in the latter cohort. A birth weight equal to or greater than 1500 g or a gestational age equal to or exceeding 32 weeks corresponded to BUN levels of 48-49 mg/dl or less. Whether the low BUN is the direct cause of the improved outcome remains to be examined.

Standard on Microbiological Management of Fluids for Hemodialysis and Related Therapies by the Japanese Society for Dialysis Therapy 2008

The Committee of Scientific Academy of the Japanese Society for Dialysis Therapy (JSDT) proposes a new standard on microbiological management of fluids for hemodialysis and related therapies. This standard is within the scope of the International Organization for Standardization (ISO), which is currently under revision. This standard is to be applied to the central dialysis fluid delivery systems (CDDS), which are widely used in Japan. In this standard, microbiological qualities for dialysis water and dialysis fluids are clearly defined by endotoxin level and bacterial count. The qualities of dialysis fluids were classified into three levels: standard, ultrapure, and online prepared substitution fluid. In addition, the therapeutic application of each dialysis fluid is clarified. Since high‐performance dialyzers are frequently used in Japan, the standard recommends that ultrapure dialysis fluid be used for all dialysis modalities at all dialysis facilities. It also recommends that the dialysis equipment safety management committee at each facility should validate the microbiological qualities of online prepared substitution fluid.

Effects of internal filtration on the solute removal efficiency of a dialyzer.

To improve solute removal efficiency, several types of dialyzers with enhanced internal filtration were introduced for clinical application. In these dialyzers, enhanced internal filtration increased convective transport of the solute, in addition to diffusive transport. In this study, the effects of internal filtration on solute removal efficiency were examined by both analytic and experimental studies. Internal filtration is affected by blood (QB) and dialysate (QD) flow rates; the patient’s hematocrit and plasma level of total protein; and the effective length (Leff), inner diameter (D), and density ratio (DR) of the hollow fibers. An analytic model was introduced for the estimation of the changes in mass and momentum along the dialyzer. It clarified the effects of these parameters on maximum internal filtration flow rate (QIF) and clearance (K) of urea (60 daltons), vitamin B12 (1,355), and myoglobin (17,000). As a result of the analytic study, QIF was increased, resulting in a smaller D, a longer Leff, and a larger DR value. Several types of dialyzers with the same cellulose triacetate membrane, produced by Toyobo Co, Ltd., Ohtsu, Japan, and Nissho Corporation, Kusatsu, Japan, were used for the experimental study. An in vitro evaluation using myoglobin solution showed the same trends as found in the analytic study. For example, a dialyzer with 150 &mgr;m of D has a 72.0 ml/min myoglobin K value, much higher than that of 53.7 ml/min for a dialyzer with 200 &mgr;m of D under constant QB (300 ml/min) and DR (50%) values. Development of a dialyzer with enhanced internal filtration, however, should take the patient’s safety into account, and hemolysis and endotoxin invasion from the dialysate to the patient should be avoided.

Solute removal characteristics of continuous recirculating peritoneal dialysis in experimental and clinical studies.

Continuous recirculating peritoneal dialysis (CRPD) was introduced to enhance solute removal efficiency in conventional peritoneal dialysis (PD) therapies such as continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a portion of the dwell dialysate in the patients peritoneal cavity is drained through a double-lumen catheter and purified by an extracorporeal dialyzer. In this study, solute removal characteristics and safety of CRPD are examined in ex vivo and clinical studies. Recirculation dialysis experiments using nine dogs (13.6 +/- 2.5 kg of body weight) were carried out for 240 min in the ex vivo study, whereas another seven dogs (12.1 +/- 2.8 kg) received conventional peritoneal dialysis (CPD) (120 min dwelling x 2) and six additional dogs (11.9 +/- 2.7 kg) received a Tidal PD (20 min dwelling x 12; 50% of tidal volume ratio) as controls. The ex vivo study revealed that CRPD has a higher efficiency for solute removal than CPD and is equivalent to Tidal PD. In the BUN reduction rate, the 19.4 +/- 5.5% in 240 min CRPD (n = 9) was significantly higher (p < 0.05) than the 3.5 +/- 3.6% in 240 min CPD (n = 7) and equivalent to the 17.3 +/- 4.7% in 240 min Tidal PD (n = 6). Continuous recirculating peritoneal dialysis maintained a low UN level in the peritoneal cavity due to dialysis with an extracorporeal dialyzer. This tendency was also seen in creatinine removal. In the clinical study, CRPD (n = 10) and CPD (n = 5) treatments were used in three renal failure patients. Higher solute removal efficiency was shown in CRPD than in CPD treatments, and the urea peritoneal clearance was 14.1 +/- 4.4 ml/min in CRPD (n = 10), significantly higher (p < 0.05) than the 7.3 +/- 2.1 ml/min in CPD (n = 5). No fibrin formation occurred during CRPD treatments.

Japanese Society for Dialysis Therapy Clinical Guideline for “Maintenance Hemodialysis: Hemodialysis Prescriptions”

Yuzo Watanabe, Hideki Kawanishi, Kazuyuki Suzuki, Shigeru Nakai, Kenji Tsuchida, Kaoru Tabei, Takashi Akiba, Ikuto Masakane, Yoshiaki Takemoto, Tadashi Tomo, Noritomo Itami, Yasuhiro Komatsu, Motoshi Hattori, Michio Mineshima, Akihiro Yamashita, Akira Saito, Hidemune Naito, Hideki Hirakata, and Jun Minakuchi, for “Maintenance Hemodialysis: Hemodialysis Prescriptions” Guideline Working Group, Japanese Society for Dialysis Therapy

Development of continuous recirculating peritoneal dialysis using a double lumen catheter.

Continuous recirculating peritoneal dialysis (CRPD) was newly introduced to improve solute removal efficiency in conventional dialysis therapies such as hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a part of the dialysate in the peritoneal cavity was drained through a double-lumen catheter and purified by an extracorporeal dialyzer. Urea removal characteristics in CRPD were examined in a canine study. In this study, a recirculation-dialysis experiment using a dog weighing 9.0 kg was carried out under 100 and 200 ml/min of flow for recirculating and delivered dialysates, respectively. An FB-50H (Nipro Medical Industries, Ltd., Osaka, Japan) composed of cellulose diacetate membrane with 0.5 m2 of surface area and Dianeal-1.5 (Baxter Limited Laboratories, Tokyo, Japan) containing urea were used as the extracorporeal dialyzer and dialysate. Urea peritoneal and dialyzer dialysances (DBP and DBD) were 3.05 and 33.3 ml/min by computer simulation using a compartment model for CRPD. This DBP value can be estimated as 20.3 ml/min for a 60 kg human. From this result, time-averaged value for BUN over an 8 hr/day CRPD, combined with three exchanges/day as CAPD is estimated to be 34.3 mg/dl, which is much lower than 45.2 mg/dl for a 12 hr/week HD, or 53.0 mg/dl for conventional CAPD.

Validity of Internal Filtration-Enhanced Hemodialysis as a New Hemodiafiltration Therapy

In order to improve solute removal efficiency, several types of dialyzers with enhanced internal filtration (IF) were introduced for clinical applications. In these dialyzers, enhanced IF increased convective transport of the solute in addition to diffusive transport. Internal filtration-enhanced hemodialysis (IFEHD) defined as hemodialysis therapy using the enhanced IF dialyzer seems to be more convenient in comparison with conventional hemodiafiltration therapies because of no additional equipments such as a roller pump. In this paper, the validity of IFEHD was examined during several types of experimental studies. As a result, the experimental study with several types of enhanced IF dialyzers indicated values of relative solute clearance in an aqueous solution that were higher than unity compared to the conventional dialyzer. The K values obtained for myoglobin as a larger molecule were more than twice as high. The value of IF flow rate (QIF) was evaluated by pulsed Doppler ultrasonography. The blood flow velocity at a cross-sectional plane of the dialyzer was directly measured along the dialyzer during a bovine in vitro study using a newly developed probe slider. Doppler ultrasonography is a useful method as a bedside monitoring of the QIF value in a dialyzer because it is noninvasive for the patient. Time course of the QIF value was examined for 6 h during a bovine in vitro study. The QIF decreased within 45 min after the start of the experiment and reached constant values after that. Although creatinine and β2-microglobulin K values remained constant with time during the experiment, α1-microglobulin K values gradually and albumin K value steeply decreased with time. This is because these solutes transfer through the membrane strongly affected by fouling. The validity of IFEHD was clarified during the experimental studies. Development of a dialyzer with enhanced IF, however, should take account of the patient’s safety. Contaminations such as endotoxin invasion from the dialysate to the patient should be avoided.

In vitro Study of Removal of Protein-Bound Toxins

Protein-bound toxins are not efficiently removed by conventional hemodialysis techniques. In order to improve the removal of protein-bound toxins, we performed an in vitro study to evaluate the effects of dilution and pH change on the dissociation of protein-bound toxins from albumin. Human plasma harvested by therapeutic apheresis treatment was diluted with saline or isotonic NaHCO3 solution, and the amounts of the free fractions of indoxyl sulfate (IS) and homocysteine were determined. The results suggested that IS was dissociated easily from albumin by dilution and pH change; higher dilution was associated with more effective removal and a greater increase of the free fraction of IS. However, these methods did not facilitate dissociation of homocysteine from albumin. Effective removal of some protein-bound toxins may be achieved by applying dilution and pH change methods to blood purification techniques, such as pre-dilution on-line hemodiafiltration.

2011 JSDT standard on the management of endotoxin retentive filter for dialysis and related therapies.

The contamination of the fluids for dialysis therapy is an important factor that deteriorates the biocompatibility of HD and related therapies. In particular, microbiological contamination is considered to be an important factor that causes dialysis amyloidosis and malnutrition due to the strong physiological activity of endotoxin (ET) (1). High-performance dialyzers are more frequently used in Japan than in other countries; hence, dialysis facilities in Japan are particularly affected by the bacterial contamination of dialysis fluid when it occurs. Moreover, most of the dialysis facilities in Japan use central dialysis fluid delivery systems (CDDSs), which are considered to be less effective in suppressing microbiological contamination than systems used in other countries, which adopt single-patient dialysis machines. Although ET retentive filters (ETRFs) are indispensable for increasing the microbiological quality of dialysis fluid, they may be a source of contamination if not appropriately handled (2). Therefore, the installation of an ETRF, which is the final safety step in the purification of dialysis fluid, does not always guarantee the purity of the final fluid. Rather, it is important to manage the quality of dialysis fluid that passes through the ETRF. In 2008, the Japanese Society for Dialysis Therapy (JSDT) established the Microbiological Quality Standard for Dialysis Fluid, which merely states that users of ETRFs should handle them according to the manufacturer’s instructions (3). To date, however, no consistent standard for handling ETRFs has been given by the Japan Medical Devices Manufacturers Association. ETRFs from different manufacturers have been deployed in various dialysis facilities using procedures at the discretion of each facility. Considering this situation, the JSDT has recommended that the management of ETRFs should be standardized and has formulated the JSDT original standard for managing ETRFs with the aim of supplying safe and stable dialysis fluid. The Working Group on the Development of the ETRF Management Standard consisted of members of the JSDT Subcommittee of Scientific Academy for the Function and Efficiency of Blood Purification Therapy as well as representatives of the Japan Medical Devices Manufacturers Association and the Japan Association for Clinical Engineers. To the best of our knowledge, there are few reports with high-level evidence regarding ETRF management. Moreover, CDDSs are predominantly used in Japan and rarely used in the US and Europe, so that makes it extremely difficult to refer to overseas evidence and standards on ETRF management. Therefore, we summarized the opinion of experts based on the results of joint research with related societies, including the Japan Association for Clinical Engineers and the Japanese Society for Hemodiafiltration, as well as the standards presented by the Japan Medical Devices Manufacturers Association and the dialysisrelated International Organization for Standardization (ISO) standards. We then formulated the ETRF Management Standard through a Consensus Conference at the 55th Annual Meeting of the JSDT. Received October 2012. Address correspondence and reprint requests to Dr. Ikuto Masakane, Yabuki Hospital, 1-6-17 Honcho, Yamagata City, Yamagata 990-0885, Japan. Email: imasakan.aipod@seieig.or.jp bs_bs_banner

Development of Intermittent Infusion Hemodiafiltration Using Ultrapure Dialysis Fluid with an Automated Dialysis Machine

To reduce the potential occurrence of hypotension during a dialysis treatment, intermittent infusion hemodiafiltration (I-HDF) using back filtration with an ultrapure dialysis fluid was developed. Under typical I-HDF treatment conditions, some 200-300 ml of ultrapure dialysis fluid was infused into the blood component through the dialyzer at a rate of 100 ml/min, every 30 min. A multicenter clinical trial was carried out to evaluate the clinical effectiveness of I-HDF compared with standard hemodialysis (SHD). The peripheral blood flow rate of each patient as detected with a laser flow meter increased for each I-HDF infusion. A significantly lower value for averaged blood volume reduction was obtained with I-HDF compared with SHD in spite of there being no difference in the total amount of water removal. The amount of normalized solute removal, cleared space for inorganic phosphate and α1-microglobulin (α1-MG) during a treatment were higher with I-HDF. Moderate α1-MG K reduction was found in I-HDF due to the prevention of membrane fouling by intermittent back filtration of the dialysis fluid. I-HDF using an automated dialysis machine was effective for improvement of the peripheral circulation of dialysis patients.