Effects of reduced dialysis fluid flow in hemodialysis.

BACKGROUND: Hemodialysis is a treatment in which uremic toxins and excess water content are removed from the blood with a dialyzer and dialysis fluid. The efficiency of hemodialysis is strongly influenced by the following 3 parameters: the blood flow rate (QB), the dialysis fluid flow rate (QD), and the overall mass transfer area coefficient (K0A), an index of a dialyzer's performance. The flow ratio (QB : QD) to obtain a well-balanced dialysis efficiency is generally said to be 1 : 2. In Japan, the QB is controlled independently (from 200 to 250 mL/min) depending on individual conditions. However, the QD is usually set at around 500 mL/min regardless of the QB. MATERIALS AND METHODS: To investigate the effect on dialysis efficiency of decreasing the QD from 500 to 400 mL/min, 12 patients were divided into two groups: one in which the QB was 150 mL/min, with 1.3-m(2) membranes; and another in which the QB was 200 mL/min, with 1.6-m(2) membranes. We defined the conditions with the QD of 500 mL/min as condition A, and that with the QD of 400 mL/min as condition B. Each operating condition was assigned for 2 weeks as crossover trials. To evaluate solute removal, we calculated clearance, reduction rate, removal amount, clear space, the clear space rate, and albumin leakage. Furthermore, when dialysis efficiency decreased in condition B, we performed a supplementary test: we calculated the QB with the K0A equation to achieve a dialysis efficiency equivalent to that in condition A, defined as condition B', as the operating condition with the calculated QB and a QD of 400 mL/min, and re-evaluated. RESULTS: In condition B, a QB of 150 mL/min had no effect on the dialysis efficiency;whereas with a QB of 200 mL/min, slight yet significant differences were observed in the clearance of small molecular weight solutes. Condition B' (QB=210 mL/min) showed an equivalent or greater dialysis efficiency and demonstrated an association with theoretical values. CONCLUSIONS: In hemodialysis, the flow ratio (QB : QD) should be maintained at 1 : 2 to obtain a well-balanced dialysis efficiency. The present study has shown that the QD can be decreased while maintaining this flow ratio. A well-balanced QD setting can be financially and environmentally conscious. In addition, use of the K0A equation is a highly effective method to calculate a QB that allows an expected dialysis efficiency to be achieved in case the QD needs to be decreased uniformly, as when dialysis fluid is in short supply during times of disaster.

Use of ultrasonic cleansing in managing the couplers of dialyzer systems.

Dialysis-related complications have become a major concern as the number of patients receiving long-term maintenance dialysis increases. One cause of complications is contamination of the dialysis fluid. When dialysis fluid contaminated by bacteria or endotoxin (ET) or both has been used for a long time, cytokine production in vivo is enhanced and can lead to such complications as dialysis amyloidosis. The rate of dialysis-related complications might be reduced with a hemopurification method that uses a large amount of dialysis fluid as a substitution fluid (on-line hemodiafiltration) or an efficient dialyzer with enhanced internal filtration in which the dialysis fluid returns to the body as a replacement fluid; however, at the same time, there is an increased risk of ET entering the body because the dialysis fluid might be contaminated. Therefore, the dialysis fluid must be made aseptic, and the dialysis fluid line must be properly managed to prevent contamination of the dialysis fluid. A half-opened line is at great risk of contamination by living microbes, which can grow in dead spaces and where the flow of dialysis fluid is interrupted. The management of couplers is an important measure for maintaining cleanliness at the end of the dialysis fluid flow. We attempted to separate and regularly clean the main body of the coupler with ultrasonic equipment as a method of managing the conventional coupler. Using improved types of coupler, the water quality of the postcoupler flow was maintained at a level as high as that of the precoupler flow for the duration of the evaluation period without separate cleansing being done. Although separate once-a-week cleansing of the conventional coupler was able to keep ET values less than the detection limit, viable cell counts were unstable. On the other hand, twice-a-week ultrasonic cleansing eliminated almost all viable cells. No definite difference in ET values or viable cell counts was found between the cleansing groups, and ultrasonic cleansing was able, by itself, to provide a sufficient cleansing effect. We conclude that ultrasonic cleansing of conventional couplers is a useful method for maintaining the water quality of the postcoupler flow because the cleansing of the coupler twice or more a week is sufficient to keep the water quality of the postcoupler flow as high as that of the precoupler flow.

The performance evaluation of endotoxin retentive filters in haemodialysis.

BACKGROUND: Hemodialysis is a method for removing uremic toxins and water directly from the blood into a dialysis fluid through an artificial semipermeable membrane called a dialyzer. The ability of the dialyzer to remove uremic toxins has steadily improved, but the likelihood has also increased that bioactive substances, such as bacterial endotoxin (ET) fragments, can be transferred from the dialysis fluid into the patient's blood through the phenomena of back-diffusion and back-filtration in the dialyzer. Therefore, further efforts to improve the quality of water are required. In 2008, the Committee of Scientific Academy of the Japanese Society for Dialysis Therapy presented its new recommendations for the quality standards of dialysis fluid, but achieving and maintaining these standard values would seem difficult without installing an ET-retentive filter (ETRF). In the present study, we evaluated whether the standards for ultrapure dialysis fluid of the Japanese Society for Dialysis Therapy can be achieved and maintained by installing 3 types of ETRF for a period of 12 months. METHODS: To evaluate the quality of dialysis fluid, ET values were measured with nephelometry, and viable cell counts were determined with the membrane filter method. Changes in the basic performance of the ETRFs were evaluated by measuring their water permeability, ET-retentive capacity, and hollow-fiber membrane intensity. Moreover, the hollow-fiber membrane surfaces of the ETRFs were observed with scanning electron microscopy, and the elements of the adherent substances were identified by means of energy dispersive X-ray spectrometry. RESULTS: The ET concentrations were less than the limit of detection during the evaluation period for samples obtained at post-ETRF sites. The viable cell counts for pre-ETRF sites were approximately 10 colony-forming units/mL. However, colonies had not formed in samples obtained from the post-ETRF sites. The substances adhering to hollow fibers included the silicon from the dialysate powder, the iron from the fluid path, and the elements derived from stainless steel. Scanning electron microscopy of the ETRF hollow fibers showed no substances except the hollow fibers and the elements derived from the dialysis fluid. CONCLUSION: Installation of an ETRF is useful for achieving and maintaining the quality standards for ultrapure dialysis fluid and for preventing the entry into the blood of ETs, viable cells, and such substances as silicon and metals.

A critical role of TRPM2 in neuronal cell death by hydrogen peroxide.

A brief exposure to hydrogen peroxide (H2O2) induces severe deterioration of primary cultured neurons in vitro. We have investigated a link between the H2O2-induced neuronal death and Ca2+-permeable TRPM2 channels regulated by ADP-ribose (ADPR). In cultured cerebral cortical neurons from fetal rat, TRPM2 proteins were detected at cell bodies and neurite extensions. Application of H2O2 to the cultured neurons elicited an increase in intracellular Ca2+ concentration ([Ca2+]i) caused by Ca2+ influx and the Ca2+-dependent neuronal death in a similar concentration range. Molecular cloning of TRPM2 cDNA from rat brain revealed several differences in amino acid sequences within the Nudix box region as compared with those of human and mouse TRPM2. ADPR-induced current responses, H2O2-induced Ca2+ influx, and H2O2-induced cell death were induced in human embryonic kidney cells heterologously expressing rat TRPM2. Treatment of cultured neurons with small interfering RNA against rat TRPM2,which efficiently suppressed immunoreactive TRPM2 content and the H2O2-induced Ca2+ influx,significantly inhibited H2O2-induced neuronal death. These results suggest that TRPM2 plays a pivotal role in H2O2-induced neuronal death as redox-sensitive Ca2+-permeable channels expressed in neurons.