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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Breath ethane in dialysis patients and control subjects.

Oxidant stress may play a role in the accelerated pathology of patients on dialysis, especially in the development of cardiovascular disease, which is a frequent condition in end-stage renal disease (ESRD) patients. Measurement of hydrocarbons can be employed to assess oxidant stress since breath hydrocarbons have been directly traced to in vivo breakdown of lipid hydroperoxides. We undertook to measure ethane, a major breath hydrocarbon, in 15 control subjects, 13 patients on peritoneal dialysis (PD), and 35 patients on hemodialysis (HD). Within the HD group, we separately examined 12 diabetic and 23 nondiabetic patients. Breath samples were collected after patients had breathed purified air for 4 min, and ethane content was measured by GC and expressed as pmoles/kg-body weight-minute (pmol/kg-min). As the data for the hemodialysis patients appeared skewed, nonparametric statistical techniques were employed to analyze these data, which are reported as median and interquartile range (IQR). Ethane levels were similar in 15 control subjects (median, 2.50 pmol [1.38-3.30]/kg-min] and 13 PD patients (median, 2.51 pmol [1.57-3.17]/kg-min). Breath ethane was significantly elevated in a portion (18 of 35 patients, 52%) of the HD patients (median, 6.16 pmol [4.46-8.88]/kg-min) (p <.001 vs. control, Mann-Whitney U test). Two of the diabetic HD patients showed extremely high values of breath ethane. Breath ethane was not altered by a single hemodialysis session, suggesting that long-term metabolic processes contribute to its elevation. Measurement of breath ethane may provide insight into severity of oxidant stress and metabolic disturbances, and provide guidance for optimal therapy and prevention of pathology in patients on long-term hemodialysis.

Measurement of intraperitoneal volume by segmental bioimpedance analysis during peritoneal dialysis.

BACKGROUND: Currently, ultrafiltration during peritoneal dialysis is determined from direct measurement of weight differences between the initial filling and final draining volumes. A new technique based on segmental bioimpedance analysis (SBIA) has been developed to accurately measure intraperitoneal volume continuously during peritoneal dialysis. METHODS: Twenty-two peritoneal dialysis patients were studied in a supine position during peritoneal dialysis consisting of 4 tidal exchanges (TPD). For bioimpedance measurements, 4 electrodes were placed, 1 on each hand and foot, to inject an alternating current. Sensing electrodes were placed on the lower ribs and the buttocks on both sides of the body. Calibration of the SBIA method was performed by first filling a known volume of dialysate to establish the relationship between change in resistance and a known fluid volume in the peritoneal cavity. The increase of fluid volume in the peritoneal cavity during dwell time was considered to be equal to net ultrafiltration volume occurring during this period. These measurements were compared with those obtained by the difference in weight between the total filling and draining volumes. RESULTS: The change in intraperitoneal volumes measured by differences in weight (0.39 +/- 0.29 L) did not differ significantly from those established from SBIA (0.41 +/- 0.31 L). Bland-Altman analysis yielded limits of agreement of 0.12 L. CONCLUSION: The SBIA technique provides a continuous noninvasive approach to the measurement of changes in intraperitoneal fluid volume.

Clinical characterization of a new polymeric membrane for use in renal replacement therapy.

Renal replacement therapy makes extensive use of semi-permeable membranes, ideal requirements for such membranes are good solute transport characteristics and a low reactivity with blood. Membranes manufactured from synthetic polymers fulfil these requirements. Such membranes have asymmetric and anisotropic structures characterized by a dense layer with which the blood is in contact supported by a thicker solid structure with containing interlinked voids, providing support. The nature of the structures are critically dependent upon the polymer blend and the control of parameters during manufacture such as the temperature or additive concentrations. In this prospective study, we have evaluated the clinical performance of a new membrane manufactured from a blend of polyamide, polyarylethersulfone and polyvinylpyrrolidone (Polyflux, Gambro GmbH, Hechingen, Germany), and compared it with that of polysulfone blended with polyvinylpyrrolidone (Fresenius Polysulfone, Fresenius Medical Care, Bad Homburg, Germany), a material widely acknowledged as providing an optimal biocompatibility in terms of solute removal and complement activation. The clearance of small molecules (urea, creatinine, phosphate) for both membranes was comparable. Both membranes removed beta2 microglobulin during treatment (50.2% reduction with Polyflux and 54.5% reduction with polysulfone. This removal due to the non-selectivity of the membranes was associated with protein loss during therapy which was similar for both the membranes (7.7 g). The biocompatibility profiles of the membranes indicated slight neutropenia and platelet adhesion and minimal C3a, C5a and SC5b-9 generation which were independent of the membrane material. These findings indicate that despite the differences in microstructure of the membranes, their functional performance in the clinical setting is comparable.

On-line clearance: a useful tool for monitoring the effectiveness of the reuse procedure.

Reprocessing of a dialyzer for repeated use in the same patient is widely practiced. The dialyzer fiber bundle volume (FBV) is monitored as an indicator of the dialyzer's suitability for continued use, with standards for reprocessed dialyzers requiring a FBV of greater than 80% of a new dialyzer to be maintained. We have used on-line measurement of clearance of sodium (OLC module, Fresenius Medical Care, Walnut Creek, CA) to assess small molecule clearance changes during and between treatments for a group of 29 chronic hemodialysis patients who reused high flux polysulfone dialyzers (F80, Fresenius Medical Care, Lexington, MA) reprocessed using citric acid and heat (95 degrees C). Data pertaining to the initial, 5th, 10th, and 15th uses were analyzed and showed that, within a single dialysis session, there was a trend for the clearance to reduce throughout the treatment (p < 0.001). Overall, there was also a trend for clearances to decline with increasing number of reuses (p < 0.008). Changes in FBV occurred, but such changes remained within the guidelines suggested by standards. It is concluded that on-line clearance measurements provide a simple noninvasive method to monitor dialyzer performance over each use and between uses.

Running water: measuring water quality in a dialysis facility. Part 2.

A summary of the primary points follows: The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status, in addition to known factors such as dose of dialysis and biocompatibility of the dialyzer membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but improves the nutritional status in long-term hemodialysis patients. Water quality needs to be routinely monitored to ensure that the potential risk to patients from chemical and bacterial contaminants is minimized; this requires the implementation of a quality approach. The layout and design of the water room and water system are key to producing and maintaining high-quality dialysis fluid. Routine monitoring and preventive maintenance of the water system will ensure that high-quality dialysis fluid is delivered.

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.