Flow balance optimization and fluid removal accuracy with the Quanta SC+ hemodialysis system.

BACKGROUND: Fluid management is integral to hemodialysis, both to correct abnormalities in a patient's plasma composition and to maintain fluid balance. Consequently, accurate net fluid removal during treatment is a critical design element of hemodialysis machines. As dialyzers have evolved, with increased ranges of ultrafiltration coefficients available, it has become more challenging for dialysis machines to minimize errors in flow balance and net fluid removal. RESEARCH DESIGN AND METHODS: This paper describes the design, evaluation and experimental performance of the flow balance and ultrafiltration module of the SC+ system to deliver clinically specified fluid removal with both passive and active control measures, in laboratory conditions designed to simulate a wide range of therapies. RESULTS: The use of passive and active control allows the errors to be minimized across a wider dynamic range of conditions. For the SC+ system, the average flow balance error was 1 mL/hr with an SD of 19 mL/hr and with ultrafiltration it was 13 mL/hr and an SD of 20 ml/hr across all conditions. CONCLUSIONS: This paper demonstrates that the SC+ hemodialysis system, a small, simple and versatile CE marked device, operates within the limits required by international standards across a wide range of experimental conditions.

Enhancement of solute clearance using pulsatile push-pull dialysate flow for the Quanta SC+: A novel clinic-to-home haemodialysis system.

BACKGROUND AND OBJECTIVE: The SC+ haemodialysis system developed by Quanta Dialysis Technologies is a small, easy-to-use dialysis system designed to improve patient access to self-care and home haemodialysis. A prototype variant of the standard SC+ device with a modified fluidic management system generating a pulsatile push-pull dialysate flow through the dialyser during use has been developed for evaluation. It was hypothesized that, as a consequence of the pulsatile push-pull flow through the dialyser, the boundary layers at the membrane surface would be disrupted, thereby enhancing solute transport across the membrane, modifying protein fouling and maintaining the surface area available for mass and fluid transport throughout the whole treatment, leading to solute transport (clearance) enhancement compared to normal haemodialysis (HD) operation. METHODS: The pumping action of the SC+ system was modified by altering the sequence and timings of the valves and pumps associated with the flow balancing chambers that push and pull dialysis fluid to and from the dialyser. Using this unique prototype device, solute clearance performance was assessed across a range of molecular weights in two related series of laboratory bench studies. The first measured dialysis fluid moving across the dialyser membrane using ultrasonic flowmeters to establish the validity of the approach; solute clearance was subsequently measured using fluorescently tagged dextran molecules as surrogates for uraemic toxins. The second study used human blood doped with uraemic toxins collected from the spent dialysate of dialysis patients to quantify solute transport. In both, the performance of the SC+ prototype was assessed alongside reference devices operating in HD and pre-dilution haemodiafiltration (HDF) modes. RESULTS: Initial testing with fluorescein-tagged dextran molecules (0.3 kDa, 4 kDa, 10 kDa and 20 kDa) established the validity of the experimental pulsatile push-pull operation in the SC+ system to enhance clearance and demonstrated a 10 to 15% improvement above the current HD mode used in clinic today. The magnitude of the observed enhancement compared favourably with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session) with the same dialyser and marker molecules. Additional testing using human blood indicated a comparable performance to pre-dilution HDF; however, in contrast with HDF, which demonstrated a gradual decrease in solute removal, the clearance values using the pulsatile push-pull method on the SC+ system were maintained over the entire duration of treatment. Overall albumin losses were not different. CONCLUSIONS: Results obtained using an experimental pulsatile push-pull dialysis flow configuration with an aqueous blood analogue and human blood ex vivo demonstrate an enhancement of solute transport across the dialyser membrane. The level of enhancement makes this approach comparable with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session). The observed enhancement of solute transport is attributed to the disruption of the boundary layers at the fluid-membrane interface which, when used with blood, minimizes protein fouling and maintains the surface area.

Evaluation of one year of frequent dialysis on fluid load and body composition using calf bioimpedance technique.

OBJECTIVE: The primary aim of this study was to evaluate the effect of increased frequency of dialysis (FHD) on change in fluid status and body composition using segmental bioimpedance. APPROACH: Twelve stable HD patients were switched from 3 times/week to 6 times/week HD (FHD). Systolic blood pressure (SBP), body mass and body mass index (BMI) were measured pre- and post-HD. Calf resistance (R 5) at 5 kHz was measured using a multifrequency bioimpedance device (Hydra 4200). Calf resistivity (ρ = R 5 * area/length), normalized resistivity (CNR = ρ/BMI) and calf extracellular volume (cECV) were calculated. Fat mass was measured by Futrex body composition analyzers (Futrex 6100, Futrex Tech, Inc.). All measurements were performed at baseline (BL) and monthly for up to one year. MAIN RESULTS: Nine patients completed one year of FHD. Compared to BL, body weight and cECV decreased, and CNR increased significantly by the first month but did not change thereafter. SBP pre-HD decreased significantly by the end of the first month with further reduction until month 12. Additionally, antihypertensive medication decreased significantly from baseline by month 4 and remained stable from month 6 throughout the rest of the study. The post-HD CNR in five of nine patients reached the range of normal (>18.5 10-2 * Ohm * m3 kg-1 for males and >19.1 10-2 * Ohm * m3 kg-1 for females) after 1 year FHD. In patients who returned to 3 times/week dialysis, CNR decreased significantly in the first week, and this was associated with increases in body weight and SBP. SIGNIFICANCE: Reduction of fluid overload with no alteration of body composition was observed in this study. Accordingly, improving fluid status was confirmed by reducing BP and use of antihypertensive drugs together with increase in CNR. Measurement of fluid status by CNR in hemodialysis patients is a new method to quantitatively assess hydration potentially creating a target for volume of fluid removal.

Fluids for continuous renal replacement therapy--an evaluation of microbial integrity.

PURPOSE: We have previously demonstrated widespread microbial contamination in the dialysis and replacement fluid circuits of bicarbonate-buffered, continuous renal replacement therapies (CRRTs). It is not known whether different CRRT fluids have an impact on bacterial activity. METHODS: In this study the in vitro growth and biofilm formation associated with seven strains of bacteria (Burkholderia cepacia, Escherichia coli, Staphylococcus aureus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Pseudomonas fluorescens, and Staphylococcus epidermidis) in five CRRT fluids (Prismocitrate, Monosol S, Accusol 35, tri-sodium citrate and Ci-Ca K2) were studied. The fluids were each inoculated with light and heavy concentrations of each of the bacterial strains and incubated at 22 or 37°C for up to 72 h with and without bacterial growth medium. Bacterial growth was assessed by spectrophotometry. Biofilm formation was assessed by a standard microtiter plate assay. RESULTS: Unsupplemented fluids did not support bacterial growth or biofilm formation after 72 h incubation. When supplemented with bacterial growth medium, some fluids, in particular Accusol 35, Ci-Ca K2, and tri-sodium citrate, had an inhibitory effect on bacterial growth, although none suppressed growths across the panel of tested organisms. CONCLUSIONS: Different CRRT fluids have different impacts on bacterial growth and biofilm formation, but all remain susceptible to extrinsic contamination.

Transfer of low-molecular weight single-stranded DNA through the membrane of a high-flux dialyzer.

PURPOSE: Microbial contamination is often present in dialysate used for hemodialysis. Small single-stranded bacterial DNA sequences are capable of activating human inflammatory pathways, through mechanisms that include the Toll-like-receptor 9, and dialysis patients frequently show severe inflammation. Since these molecules have been found in dialysate and in patients' bloodstreams, we studied the potential of low-molecular weight DNA sequences, of the same structure as found in bacteria, to cross from the dialyzer circuit to the blood circuit of a dialysis filter. METHODS: The mass transfer of DNA fragments across a high-flux dialyzer was evaluated with an in vitro dialysis model, in both conventional dialysis and pure convection mode. Measurement of DNA was performed by HPLC. RESULTS: In dialysis mode, these mass transfer coefficients were calculated for different single-stranded DNA chain lengths: 5-bases = 28.5%, 9-bases = 20.5%, 20-bases = 9.4%, 35-bases = 2.4%, 50-bases and 100-bases, no transfer detected. In convection mode, these sieving coefficients were calculated: 5-bases = 1.0, 9-bases = 1.0, 20-bases = 0.68, 35-bases = 0.40, 50-bases = 0.17, 100-bases, no convective transfer detected. The physical size of DNA molecules could be the major factor that influences their movement through dialyzer pores. CONCLUSIONS: This study establishes that significant transfer across the dialyzer may occur with single-stranded DNA in the size range of 20-bases or less. These findings need to be confirmed with an in vitro whole blood model and with clinical investigations. Previous studies have described the clinical benefits of achieving high-purity dialysate. Precautions are warranted to minimize the presence of these DNA compounds in fluids utilized for hemodialysis treatment.

Hospitalization and mortality in hemodialysis patients: association with hemoglobin variability.

BACKGROUND/AIMS: Hemodialysis patients show complications associated with low or high hemoglobin (Hb), which occur frequently in clinical practice. We sought to determine the clinical importance of these changes in Hb levels. METHODS: From our clinic cohorts, we identified 1,634 who met inclusion criteria for analysis of hospitalization frequency and 1,953 analysis of mortality; many patients were in both groups. Hb excursions outside the target range (11-12.5 g/dl) were studied in relation to patient outcomes. RESULTS: Hb measures below range were associated with more frequent hospitalization (p < 0.001), increased length of stay (p < 0.001), and increased mortality (p < 0.01), whereas Hb above range was associated with a reduced frequency of hospitalization (p < 0.01) and shorter length of stay (p < 0.01), and tended to be associated with reduced mortality. CONCLUSIONS: Excursions below range were associated with negative outcomes, but excursions above range were either beneficial or neutral. Our findings indicate that clinicians should focus on low Hb as a negative indicator of patient status, whereas transient Hb above range is a marker for patient health and well-being.

Perspectives in home hemodialysis therapy.

Currently, there is renewed interest in home hemodialysis. However, home hemodialysis is not for every patient--the majority will continue to need treatment away from their home in hospital or satellite units. Those who are capable of undertaking treatment at home should be strongly encouraged to do so. Treatment at home permits improved quality of life and rehabilitation, and is cost-effective. However, it needs nephrologists versed in the techniques and benefits of home hemodialysis as well as nursing staff capable of undertaking the training, underpinned by a well-functioning predialysis program geared towards identifying and recruiting patients suitable for home hemodialysis well before dialysis is required. This review explores the origins, decline and reawakened interest in this treatment modality, and discusses novel technological approaches to ease the patient's treatment burden.

Water for haemodialysis and related therapies: recent standards and emerging issues.

Dialysis is a well-established and widely used procedure. For a number of years, the focus has been on ensuring that water used in the preparation of dialysis fluid meets the required chemical and microbiological quality and complies with national or international standards which have recently been updated. Continued vigilance is required, in particular when new chemicals such as silver-stabilized hydrogen peroxide and chlorine dioxide are used to prevent growth of Legionella bacteria in hospital water systems, since residues are harmful to patients receiving dialysis. To achieve the required quality, large volumes of water are processed, and a substantial portion is sent to waste via the municipal sewer systems with little attempt to reuse such water on site. In view of concern about global warming and climate change, there is a need to adopt a more environmentally conscious attitude requiring dialysis providers to focus on this aspect of water usage.

How do changes in water quality and dialysate composition affect clinical outcomes?

Dialysis relies upon the transfer of waste products and electrolytes across a semi-permeable membrane contained in the dialyser facilitated by the dialysis fluid, a fast-flowing electrolyte solution prepared continuously by the mixing of treated water with a concentrated electrolyte solution. Both the water, the buffer and electrolyte composition play important roles in modulating complications associated with treatment. With respect to water, historically the focus was on chemical contaminant content, but more recently has shifted to microbiological quality due to the role that such quality plays in the pro-inflammatory state. The composition of the dialysis fluid is crucial in normalization of electrolyte composition of plasma water, homeostasis and acid-base balance, and should be individualized to the patients' requirements in the same way as blood and dialysate flow rates are individualized to ensure optimal comfort and minimal complications associated with the procedure.

Disinfection of the hospital water supply: a hidden risk to dialysis patients.

Water suitable for drinking is unsuited for use in the preparation of haemodialysis fluid and undergoes additional treatment. The primary component of the additional treatment is reverse osmosis, which does not remove low-molecular-weight contaminants, and the water treatment system must contain carbon beds or filters to ensure effective removal of such contaminants. The recent article by Bek and colleagues highlights an unrecognised issue with respect to chemicals that may be added to the water within hospitals to ensure that the distribution network is free of pathogens (for example, Legionella, pseudomonas, and mycobacteria) and underlines the need for personnel responsible for dialysis in a renal or intensive care setting to be aware of any potential effects that disinfection of the hospital water treatment system may have on the product water used in the preparation of dialysis fluid. Such awareness requires communication and the sharing of information between clinical and facilities staff.

A microbiological survey of bicarbonate-based replacement circuits in continuous veno-venous hemofiltration.

OBJECTIVE: The potential for clinically significant transfer of pyrogen-inducing material in dialysate and substitution fluids is well recognized in the setting of chronic hemodialysis and hemodiafiltration and has led to the establishment of strict standards for microbiological purity. Preliminary evidence has indicated the potential for fluid contamination in continuous renal replacement therapy, and although the scale of the problem in contemporary, industry-standard equipment is unclear. We aimed to define the microbial integrity of modern continuous veno-venous hemofiltration (CVVH) replacement fluid circuitry. DESIGN: Twenty-four CVVH replacement fluid circuits (mean lifespan, 34.2 hours; range, 4-86) were studied at completion of therapy. SETTING: The integrated critical care unit and cardiothoracic intensive care unit of the Freeman Hospital, Newcastle upon Tyne, United Kingdom, between January and August 2007. SUBJECTS: Patients with renal failure receiving treatment with CVVH. INTERVENTIONS: Nil. MEASUREMENTS: Culture and endotoxin assays of replacement fluid, culture of endoluminal swabs, and electron microscopy of harvested tubing. MAIN RESULTS: Of the 24 replacement fluid cultures, nine (mean lifespan 32.8 hours, range 5-79) breached European Pharmacopoeia standards for ultrapure water (<0.1 colony-forming units/mL). One of 24 endotoxin measurements breached European Pharmacopoeia standards (<0.03 endotoxin units/mL). Internal tubing cultures were negative, but electron microscopy revealed 13 of the 24 collected tubing samples to be contaminated with biofilm. Only seven of the 24 studied circuits proved to be free from microbial contamination. CONCLUSIONS: We have confirmed frequent breaches of microbial integrity in industry-standard, bicarbonate-based CVVH, indicating the potential for added risk to the vulnerable, critically ill patient. These findings are of particular concern given the need for systemic infusion of replacement fluid. Measures to reduce the levels of contamination and their impact are discussed.

Water treatment for dialysis: technology and clinical implications.

The dialytic process utilizes high volumes of water in the preparation of the dialysis fluid. Improvements in water treatment equipment have resulted in improvements in chemical quality. Awareness that endotoxin and bacterial fragments present in the water distribution loop within the dialysis, are able to cross the dialyser membrane, has resulted in an increased focus on this aspect of water quality. Practically, the age of many water treatment plants, extensions of distribution systems and suboptimal cleaning procedures have prevented the achievement of optimal microbiological quality on a routine basis. When achieved and maintained, clear benefits to the patient have been demonstrated. Hemodialysis patients are also subject to increased oxidative stress which may also contribute to their morbidity and mortality. Recent clinical studies using dialysis fluid made with electrolytereduced water have demonstrated benefits to antioxidant status of dialysis patients, offering a further technological solution to the problem of increased cardiovascular disease in dialysis patients.

Impact of water quality and dialysis fluid composition on dialysis practice.

An essential but frequently neglected aspect of dialysis treatment is the dialysis fluid produced by blending treated tap water with concentrated solutions containing electrolytes and buffer. Chemical and microbiological contaminants as well as the electrolyte and buffer composition of the dialysis fluid play major roles in the induction or modulation of morbidity associated with regular dialysis therapy.

Differential effects of dialysis and ultrafiltrate from individuals with CKD, with or without diabetes, on platelet phosphatidylserine externalization.

Individuals with chronic kidney disease (CKD) and/or diabetes mellitus (DM) are at increased risk of cardiovascular events and have elevated externalization of phosphatidylserine (PS; which propagates thrombus formation) in a small subpopulation of platelets. The purpose of this study was to examine the effect of 1) removing uremic toxins by hemodialysis on PS externalization in patients with either CKD or CKD and DM and 2) ultrafiltrate (UF) from these individuals on PS externalization in healthy platelets. PS externalization was quantified by a fluorescence-activated cell sorter using annexin V in platelet-rich plasma. PS externalization was elevated threefold in CKD patients and returned to basal values during 3-h hemodialysis. In contrast, it was elevated fivefold in individuals with CKD and DM and was still threefold above control after 3-h treatment. UF significantly increased PS externalization in a small subpopulation of platelets from healthy controls. The effect of UF from individuals with CKD and DM was significantly greater than that from patients with CKD alone, and the responses were partially inhibited by the protein kinase Cdelta (PKCdelta) inhibitor rottlerin and the 5-hydroxytryptamine (5-HT)(2A/2C) receptor antagonist ritanserin. The data suggest that uremic toxins present in UF mediate PS externalization in a small subpopulation of platelets, at least in part, via the 5-HT(2A/2C) receptor and PKCdelta and demonstrate that DM further enhances platelet PS externalization in CKD patients undergoing hemodialysis. This may explain, at least in part, the additional increase in vascular damage observed in CKD patients when DM is present.

Membranes and filters for haemodiafiltration.

Online haemodiafiltration is an extracorporeal technique, utilizing highly permeable and highly biocompatible membranes, which permits the combination of convective and diffusive solute removal from the blood and offers increased removal of medium-weight uraemic solutes, compared to the more frequently used low-and high-flux haemodialysis. The objective of this chapter is to review the membranes and filters available for haemodiafiltration and to discuss factors that influence their performance during clinical use.

Advanced glycation end products elicit externalization of phosphatidylserine in a subpopulation of platelets via 5-HT2A/2C receptors.

Advanced glycation end products (AGE) are substantially elevated in individuals with diabetes and/or chronic kidney disease (CKD). These patients are at greatly increased risk of cardiovascular events. The purpose of this study was to investigate the novel hypothesis that AGE elicit externalization of the platelet membrane phospholipid phosphatidylserine (PS). This contributes to hemostasis through propagation of the coagulation cascade leading to thrombus formation. Platelet-rich plasma (PRP) was prepared by differential centrifugation, and PS externalization was quantified by a fluorescence-activated cell sorter using annexin V-FITC. Human serum albumin (HSA)-AGE was generated by incubating HSA with glucose for 2, 4, or 6 wk, and total HSA-AGE was assessed by fluorescence intensity. The 2-wk HSA-AGE preparation (0-2 mg/ml) stimulated a concentration-dependent increase in PS externalization in a subpopulation of platelets that was threefold at 2 mg/ml. In contrast, the 4- and 6-wk preparations were maximal at 0.5 mg/ml and fivefold in magnitude. These effects mirrored the change in total HSA-AGE content of the preparations. The PS response was maximal at 10 min and inhibited by the PKC-delta inhibitor rottlerin and the serotonin [5-hydroxytryptamine (5-HT)](2A/2C) receptor antagonist ritanserin in a dose-dependent manner. Moreover, the 5-HT(2A/2C) receptor agonist 1,2,5-dimethoxy-4-iodophenyl-2-aminopropane mimicked the effect of HSA-AGE on PS externalization. These data demonstrate, for the first time, that HSA-AGE stimulates PS externalization in a subpopulation of platelets via the 5-HT(2A/2C) receptor. This may have important consequences for platelet involvement in inflammatory responses and the increased cardiovascular risk observed in individuals with diabetes and/or CKD.