Clinical benefits of ultrapure dialysis fluid for hemodialysis

Ultrapure dialysis fluid contains less than 0.1 CFU/mL and 0.03 EU/mL and can be prepared by ultrafiltration of standard‐quality dialysis fluid. Today, the use of ultrapure dialysis fluid is widely recommended based on our awareness of potential transfer of bacterial products across dialysis membranes. Early observations associated improved fluid quality with reduced incidence of the carpal tunnel syndrome, but provided no proof of mechanism. Recent clinical studies in hemodialysis patients have shown that the introduction of ultrapure dialysis fluid brings about significant improvements in a number of inflammation‐related parameters. Levels of C‐reactive protein and IL‐6 are reduced, anemia management is achieved using less EPO or reaching higher hemoglobin levels, nutritional indices are improved, and β₂‐microglobulin levels have been observed to decline, when ultrapure dialysis fluid is used in comparison with standard‐quality fluid. In addition, some studies have documented reduced levels of advanced glycation end products and delayed decline of residual renal function in patients using ultrapure dialysis fluid. Although further evidence is needed before we can assess the long‐term benefits associated with improved fluid quality, there should be sufficient data available today to support our efforts toward gradual improvement of the microbiological quality of dialysis fluid.     

Endotoxemia after high cutoff hemodialysis for treatment of patient with multiple myeloma can be prevented by using ultrapure dialysate: A case report

To report endotoxemia presented in a case with multiple myeloma (MM) treated by high cutoff hemodialysis (HCO‐HD) being prevented by using ultrapure dialysate. A female inpatient with MM received six times HCO‐HD (HCO 2100 dialyzer) within 3 weeks after initiation of a chemotherapy based on vincristine + epirubicin + dexamethasone protocol. Conventional dialysate was used in the first three times and then changed to ultrapure dialysate due to elevation of body temperature after HCO‐HD. Free light chains (FLC) and endotoxin levels in blood and dialysate were monitored. After six times HCO‐HD, her serum FLC λ decreased from 4689 mg/L to 492.7 mg/L, with a trend of decline of serum creatinine. The clearance, reduction ratio, and removal amount of FLC λ was 38.4 mL/min, 71.0–85.2%, and 9.06–18.02 g, respectively, in the setting of dialysate flow rate 500 mL/min, while in the setting of dialysate flow rate 200 mL/min, the removal efficacy of FLC λ was lower than the former. A rise of body temperature up to 38.5°C after treatment and endotoxemia (endotoxin levels 0.122 EU/mL) was found when using conventional dialysate (endotoxin levels 0.112–0.145 EU/mL), but not seen after changing to ultrapure dialysate. Combined with appropriate chemotherapy, HCO‐HD can effectively remove and reduce blood FLC. Attention should be paid to the endotoxemia and the rise of temperature after treatment when conventional dialysate is used, which can be prevented by using ultrapure dialysate.     

Impact of advanced dialysis technology on the prevalence of dialysis‐related amyloidosis in long‐term maintenance dialysis patients

Dialysis‐related amyloidosis (DRA) is a unique type of amyloidosis (beta‐2 microglobulin) predominantly in end‐stage renal disease. Its clinical manifestations add to increased morbidity and reduced quality of life. There seems to be a relative risk reduction in DRA manifestations when hemodialysis (HD) patients are treated with advanced HD technology, but changes of the course of DRA are uncertain. The aim of our investigation was to evaluate the prevalence and severity of carpal tunnel syndrome (CTS) in long‐term dialysis patients receiving either conventional or high‐flux, online‐produced ultrapure dialysis fluid. The cross‐sectional study included 147 HD patients (at least 10 years). The definitive diagnosis of CTS was made histologically or by the coexistence of CTS with other radiological DRA manifestations (bone cysts, arthropathies). The two HD patient groups did not differ significantly in age at start of HD, gender, major co‐morbid diseases, anuria, and dialysis vintage. The conventional HD group had significantly higher circulating beta‐2 microglobulin and C‐reactive protein (CRP) levels. The prevalence of DRA was 68% for the conventional HD group and 28% for the advanced HD group. Duration of dialysis treatment was the only significant risk factor for the development of clinical DRA manifestations in both study groups, but CTS, bone cysts, or arthropathies occurred significantly earlier in conventional HD patients. The prevalence and severity of DRA have decreased with advances in dialysis technology during the last two decades, although its occurrence is simply delayed.     

Dialysate saving by automated control of flow rates: comparison between individualized online hemodiafiltration and standard hemodialysis

Cost reduction and quality improvement seem to be conflicting issues. However, online hemodiafiltration (oHDF) with new automatic functions offers a cost‐efficient therapy compared to hemodialysis (HD). Seven dialysis centers conducted a randomized clinical trial with cross‐over design: high‐flux HD vs. postdilutional oHDF with functions coupling both dialysate and substitution flow rates to blood flow rates. During the 6 weeks of the study, all treatment parameters remained unchanged for HD and oHDF, apart from dialysate and substitution flow rate. Treatment data were recorded during each treatment, and predialytic and postdialytic concentrations of urea were recorded at the end of each study phase. The analysis involved 956 treatments of 54 patients. The mean dialysate consumption was 123.2 ± 6.4 l for HD and 113.4 ± 14.9 l for oHDF (p < 0.0001), the mean dialysis dose was 1.42 ± 0.23 for HD and 1.47 ± 0.26 for oHDF (p < 0.0001); oHDF resulted in a lower dialysate consumption (8.0% less) and a slightly increased dialysis dose (Kt/V 3.5% higher) compared to HD. oHDF with the investigated automatic functions offers substantial savings in dialysate consumption without decreasing dialysis dose.     

Beyond ultrapure hemodialysis: A necessary and achievable goal

Survival of chronic hemodialysis patients is worse than that of many patients with cancers or severe infections. An important cause of chronic inflammation is impurities infused into patients during dialysis. Definitions of dialysis purity have been narrow and focused on metals in dialysate water and on bacterial contaminants. There is no standard for priming fluids or toxins released directly into blood from inside the extracorporeal circuit. We propose a much broader standard of dialysis purity that also includes phthalate metabolites, bisphenols, spalled particles, and other contaminants from dialysis machines, filters, and bloodlines. Standards must include new methods for measuring bacteriological contaminants in addition to colony‐forming units and endotoxin determinations. These include the sensitive silkworm larva plasma test that detects peptidoglycan that is missed by endotoxin tests and standards for newly detected small molecular bacterial detritus. Current levels for “standard” bacteriological contaminants are woefully inadequate and should be increased. New standards for contamination with plasticizers and spallation are also necessary. Studies with ultrapure dialysis have shown almost immediate patient benefits with increased well‐being and stabilization of the cardiovascular system during and between dialyses. Intermediate effects include lower C‐reactive protein levels, better response to erythropoietin, increased appetite, and improved nutrition. Over the years, amyloidosis and carpal tunnel syndrome have become less common and cardiovascular deaths have decreased. Standards for dialysis purity must be sharpened and expanded and this becomes even more urgent with daily and long nightly hemodialysis. All contaminants received by patients, whether biological, chemical, or physical, must be considered.     

Determination of the critical absolute blood volume for intradialytic morbid events

The reduction of blood volume below a critical threshold is assumed to trigger intradialytic morbid events (IME). Recently, we presented a simple method to determine the absolute blood volume during routine hemodialysis (HD) carried out without blood sampling and without injection of dyes or radiolabeled markers. Such information could be used to detect excessive volume reduction during HD and to prevent IME. Therefore, we performed a pilot study in IME‐prone patients to identify the absolute blood volume at which they developed clinical symptoms. A volume of 240 mL of ultrapure dialysate was automatically infused into the extracorporeal circulation using the bolus function of a commercial online hemodiafiltration machine incorporating a blood volume monitor (BVM). The increase in relative blood volume (RBV) caused by the infusion was measured and used to determine the absolute blood volume at that time. The blood volume per kilogram body mass at the time of symptomatic IME was also determined. All IME‐prone patients of a single‐dialysis center were included in the study. Ten out of 12 patients became symptomatic at a specific blood volume between 65 and 56 mL/kg (mean 62 mL/kg) whereas RBV showed a wide scatter (82–97%). A specific blood volume of 65 mL/kg seems to represent the threshold for IME by this method. The technique could be completely automated without altering the hardware of the dialysis device. Present feedback systems for automated blood volume‐controlled ultrafiltration could be adapted to maintain absolute blood volume above this critical volume to safely prevent volume‐dependent IME.     

Management of hypophosphatemia in nocturnal hemodialysis with phosphate-containing enema: a technical study

Hypophosphatemia is observed in patients undergoing nocturnal hemodialysis. Phosphate is commonly added to the dialysate acid bath, but systematic evaluation of the safety and reliability of this strategy is lacking. The objectives of this study were 4‐fold. First, we determined whether predictable final dialysate phosphate concentrations could be achieved by adding varying amounts of Fleet^® enema. Second, we assessed the stability of calcium (Ca) and phosphate dialysate levels under simulated nocturnal hemodialysis conditions. Third, we assessed for Ca‐phosphate precipitate. Finally, we evaluated whether dialysate containing Fleet^® enema met the current sterility standards. We added serial aliquots of enema to 4.5 L of dialysate acid concentrate and proportioned the solution on Gambro and Althin/Baxter dialysis machines for up to 8 hours. We measured dialysate phosphate, Ca, pH, and bicarbonate concentrations at baseline, and after simulated dialysis at 4 and 8 hours. We evaluated for precipitation visually and by assessing optical density at 620 nm. We used inoculation of agar to detect bacteria and Pyrotell reaction for endotoxin. For every 30 mL of Fleet^® (1.38 mmol/mL of phosphate) enema added, the dialysate phosphate concentration increased by 0.2 mmol/L. There were no significant changes in dialysate phosphate, Ca, pH, and bicarbonate concentrations over 8 hours. No precipitate was observed in the dialysate by optical density measures at 620 nm for additions of up to 90 mL of enema. Bacterial and endotoxin testing met sterility standards. The addition of Fleet^® enema to dialysate increases phosphate concentration in a predictable manner, and no safety problems were observed in our in vitro studies.     

Endotoxins and inflammation in hemodialysis patients

Long‐term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so‐called MIA syndrome. Circulating soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C‐reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM‐1 was estimated using enzyme‐linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (<6.0 mg/L). A statistically significant correlation was found between endotoxin and CRP levels (r = 0.47, P = 0.001). The mean pre‐HD level of VCAM was 1851.00 ng/mL, while the mean post‐HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post‐HD rise in sVCAM‐1.     

Quality of water in hemodialysis centers in Baghdad,Iraq

Dialysis water quality is one of the important parameters all over the world because of its direct influence on the health of kidney patients. In Iraq, there are more than 20 dialysis centers; most of them contain identical units for the production of dialysis water. In this work, the quality of water used for dialysis in six dialysis centers located within Baghdad hospitals was evaluated. Samples of product water from each of the six dialysis centers were examined for total heterotrophic bacteria, endotoxin, and chemical contaminants. Endotoxin was measured on‐site using a portable instrument. Bacteriological and chemical examinations were done in the laboratory after collecting samples from each dialysis center. The results showed a fluctuation in the produced water quality that makes the produced water unaccepted when compared with international standards. Bacterial counts for 60% of the analyzed samples were above the action level (50 colony‐forming units[CFU]/mL), while five out of the six dialysis centers showed values higher than the maximum value (100 CFU/mL). Chemical analysis showed that the dialysis water quality suffers from elevated aluminum concentration for all dialysis centers. All hemodialysis centers need thorough monitoring and preventive maintenance to ensure good water quality. In addition, it is important to revise the design of the water treatment units according to the feed and product water quality.     

Intensive dialysis and blood pressure control: A review

The prevalence of hypertension in hemodialysis (HD) patients has increased over the years. In the early days of maintenance HD blood pressure (BP) control was achieved in most patients. As sessions were shortened, the prevalence of hypertension increased. Yet, in principle, dialysis is able to control hypertension. Today, in programs using long HD, most patients are normotensive without antihypertensive medication. The same is true for patients on daily dialysis, but not for those on short thrice‐weekly HD. In all studies reporting BP normalization, dry weight is regularly achieved. Why the poor control of hypertension now? At first sight the shortened session duration is the culprit. This is suggested by several epidemiologic observations and strongly supported by a prospective experience of changing the HD schedule (short to long HD or conversely) in the same group of patients. Recent studies, however, using strict volume control show that BP normalization can be obtained in conventional 3 x 4 hr/week dialysis with relatively low delivered Kt/V_urea. Therefore, prolonging the dialysis time and/or increasing the dialysis dose are not required to achieve BP control. Intensive dialysis most probably normalizes BP by getting the extracellular volume and the amount of sodium in the body back to normal. It acts in conjunction with a moderate dietary sodium restriction and the use of reasonably low dialysate sodium. With this approach improved BP control can be achieved in the vast majority of HD patients.     

Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end‐stage renal disease (ESRD) patients treated by hemodialysis (HD). Although traditional risk factors are common in dialysis patients, they may not alone be sufficient to account for the unacceptable high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor that is commonly observed in HD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The cause(s) of inflammation in HD patients is multifactorial and includes both dialysis‐related (such as graft and fistula infections, bioincompatibility, impure dialysate, and back‐filtration) and dialysis‐unrelated factors. Although inflammation may reflect underlying CVD, an acute‐phase reaction may also be a direct cause of vascular injury. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there is not yet any recognized, or even proposed, targeted treatment for ESRD patients with chronic inflammation; it would be of considerable interest to study the long‐term effect of various anti‐inflammatory treatment strategies on nutritional and cardiovascular status as well as outcome in these patients.     

A study of 8 hour long night dialysis with the Aksys PHD dialysis system

The Aksys PHD system is designed for short quotidian dialysis employing a 52‐liter batch of ultrapure dialysate and up to 30 in situ hot water reuses of the entire extracorporeal circuit including a 40‐liter physical cleaning before each dialysis. Methods:  We studied the effect of the 52‐liter tank during 108 long 5–8 hour dialysis 3.5–6 times/week in 5 patients and one 50‐liter patient simulator for 4 weeks. Phosphate (PO₄), beta‐2 microglobulin (b‐2), urea (BUN), and creatinine (creat) were measured pre‐, during, and post‐dialysis 86 times and in total dialysate 74 times during long dialysis. Tank saturation, Kt/V, and monthly chemistries were also measured. Results:  Patient weight 76 ± 2 kg, QB 234 ± 23 ml/min, QD 498 ± 13 ml/min. Dialysate was recirculated 4.8 times during 8 hours.  

     

Microbial quality of hemodialysis water,a survey of six centers in Lagos,Nigeria

Patients with end‐stage kidney disease (ESRD) on maintenance hemodialysis (HD) are usually exposed to large volumes of dialysate, which is separated from patients' blood only by thin membrane of dialyzer. It is therefore essential to frequently monitor the quality of HD water to ensure that it meets the recommended standards. The objective of this study was to evaluate the microbial quality of HD water in Lagos, Nigeria. Four sets of pre‐ and post‐treatment water samples, 20 mL each, were collected from six HD centers in Lagos and tested for microbial contamination using the molten Tryptic soy agar in accordance with Association for Advancement of Medical Instrumentation (AAMI) and European Best Practice Guidelines (EBPG). Pyrogen tests were also conducted on pre‐ and post‐treatment samples using standard technique. Information on water treatment modalities, maintenance practices and quality control measures in each center were obtained using a questionnaire. All centers use treated water for HD purpose. None of the HD centers met EBPG/AAMI guidelines for microbial contaminants as the mean levels of Escherichia coli in both feed and treated water were 441.7 ± 87.90 and 168.5 ± 64.03, respectively. E. coli was the commonest organism isolated in both feed and treated water in all the centers. HD water quality is still a neglected problem in our environment and more efforts are required to ensure good water quality for HD purpose.     

Calculation of the clearance requirements for the development of a hemodialysis‐based wearable artificial kidney

Wearable artificial kidney (WAK) has been considered an alternative to standard hemodialysis (HD) for many years. Although various novel WAK systems have been recently developed for use in clinical applications, the target performance or standard dose of dialysis has not yet been determined. To calculate the appropriate clearance for a HD‐based WAK system for the treatment of patients with end‐stage renal disease with various dialysis conditions, a classic variable–volume two‐compartment kinetic model was used to simulate an anuric patient with variable target time‐averaged creatinine concentration (TAC), daily water intake volume, daily dialysis pause time, and patient body weight. A 70‐kg anuric patient with a HD‐based WAK system operating for 24 h required dialysis clearances of creatinine of at least 100, 50, and 25 mL/min to achieve TACs of 1.0, 2.0, and 4.0 mg/dL, respectively. The daily water intake volume did not affect the clearance required for dialysis under various conditions. As the pause time per day for the dialysis increased, higher dialysis clearances were required to maintain the target TAC. The present study provided theoretical dialysis doses for an HD‐based WAK system to achieve various target TACs through relevant mathematical kinetic modeling. The theoretical results may contribute to the determination of the technical specifications required for the development of a WAK system.     

Comparison of techniques for culture of dialysis water and fluid

Introduction: Microbiological culture of dialysis water and fluid is a routine safety measure. In the United States (U.S.), laboratories perform these cultures on trypticase soy agar at 35–37°C for 48 h (TSA‐48h), not on the tryptone glucose extract agar or Reasoner's 2A agar at 17–23°C for 7 days (TGEA‐7d and R2A‐7d, respectively) recommended by international standards. We compared culture methods to identify samples exceeding the accepted action level of 50 CFU/mL. Methods: Dialysis water and fluid samples collected from 41 U.S. dialysis programs between 2011 and 2014 were cultured at two U.S. laboratories. Each sample was cultured using (1) either TGEA‐7d or R2A‐7d and (2) TSA‐48h. We compared proportions exceeding the action level by different methods and test characteristics of TSA‐48h to those of TGEA‐7d and R2A‐7d. Findings: The proportion of water samples yielding colony counts ≥50 CFU/mL by TGEA‐7d was significantly different from the proportion by TSA‐48h (P = 0.001; difference in proportion 4.3% [95%CI 1.3–7.3%]). The proportions of dialysis fluid samples ≥50 CFU/mL by TGEA‐7d and TSA‐48h were not significantly different; there were no significant differences for comparisons of R2A‐7d to TSA‐48h. Discussion: In dialysis fluid, TSA‐48h was comparable to TGEA‐7d and R2A‐7d in identifying samples as having bacterial counts ≥50 CFU/mL. In dialysis water, TSA‐48h was comparable to R2A‐7d in identifying samples ≥50 CFU/mL, but TGEA‐7d did yield significantly more results above 50 CFU/mL. Nonetheless, the negative predictive value of a TSA‐48h result of <50 CFU/mL in dialysis water exceeded 95%.     

Metformin intoxication requiring dialysis

Metformin (MTF) is one of the most common oral agents used to treat diabetes mellitus. Intoxication is associated with lactic acidosis and has significant clinical consequences. We report 12 cases requiring dialytic intervention. Twelve patients were analyzed from 2005 to 2010; 10 of these patients were treated with dialysis. Conventional hemodialysis (HD) and continuous veno-venous hemodialysis treatments with bicarbonate dialysis were used, and the results were presented as mean and standard deviation. The results are as follows: 33% of the patients were male, hospital stay was 9.3 (± 12) days, average MTF dose 1.7 g/day, mortality was 25%. Baseline glomerular filtration rate for these patients was 51.5?mL/min, with an average age of 64 (± 11) years. On presentation, all had acute kidney injury with blood urea nitrogen/creatinine 75 (± 30)/8.1 (± 3.7) mg/dL, lactic acid 12.4 (± 8.1) mmol/L, pH?7.04 (± 0.19), bicarbonate 7.2 (± 4.5) mmol/L. Metformin level was 25 (± 17) μg/mL; anion gap was 28 (± 9), and serum potassium was 5.4 (± 1.3) mEq/L. Seventy percent of patients were treated with conventional HD. Patients required 4 (± 5) dialysis treatments at blood flow QB 330 (± 53), dialysis flow QD 571 (± 111) for 305 (± 122) minutes. Postdialysis, the acidosis parameters improved: bicarbonate 19.2 (± 4.1) mmol/L, lactic acid 6 (± 4) mmol/L and MTF levels decreased 8.9 (± 5.7) μg/mL. Metformin percentage removal was calculated to be 60% (± 24). No difference was found between HD and continous veno-venous hemodialysis. The only difference between survivors was the age 53 (± 7) vs. 78 (± 10) (P?相似文献   

Solute kinetics with short-daily home hemodialysis using slow dialysate flow rate

"NxStage System One^™" is increasingly used for daily home hemodialysis. The ultrapure dialysate volumes are typically between 15 L and 30 L per dialysis, substantially smaller than the volumes used in conventional dialysis. In this study, the impact of the use of low dialysate volumes on the removal rates of solutes of different molecular weights and volumes of distribution was evaluated. Serum measurements before and after dialysis and total dialysate collection were performed over 30 times in 5 functionally anephric patients undergoing short-daily home hemodialysis (6 d/wk) over the course of 8 to 16 months. Measured solutes included β₂ microglobulin (β₂M), phosphorus, urea nitrogen, and potassium. The average spent dialysate volume (dialysate plus ultrafiltrate) was 25.4±4.7 L and the dialysis duration was 175±15 min. β₂ microglobulin clearance of the polyethersulfone dialyzer averaged 53±14 mL/min. Total β₂M recovered in the dialysate was 106±42 mg per treatment (n=38). Predialysis serum β₂M levels remained stable over the observation period. Phosphorus removal averaged 694±343 mg per treatment with a mean predialysis serum phosphorus of 5.2±1.8 mg/dL (n=34). Standard Kt/V averaged 2.5±0.3 per week and correlated with the dialysate-based weekly Kt/V. Weekly β₂M, phosphorus, and urea nitrogen removal in patients dialyzing 6 d/wk with these relatively low dialysate volumes compared favorably with values published for thrice weekly conventional and with short-daily hemodialysis performed with machines using much higher dialysate flow rates. Results of the present study were achieved, however, with an average of 17.5 hours of dialysis per week.