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.

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.

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.

Haemodialysis fluid: composition and clinical importance.

Dialysis fluid is produced by the blending of treated water with electrolytes at the patients bed side. Its preparation and composition are important elements of treatment optimisation since many of the constituents play a role in patient well-being. Ideally the composition of the dialysis fluid should match that of plasma, but due to differences between patients, as well as the increasing number of elderly patients receiving treatment, have resulted in a move towards individualisation of the electrolyte and buffer composition to patient needs. Such individualisation is facilitated by the availability of technology, however it is not yet possible to individualise minor electrolytes, such as K(+), Ca(2+) and Mg(2+). Early dialysis treatments were frequently accompanied by pyrogen reactions arising from bacterial contamination of the dialysis fluid. Today the focus is on the stimulation of mononuclear cells by bacterial fragments contributing to chronic inflammation associated with long-term haemodialysis therapy, and which has led to suggestions regarding the desirability of using ultra-pure dialysis fluid to prevent or to delay complications associated with their presence.

The importance of water quality and haemodialysis fluid composition.

Treatment of renal failure by haemodialysis uses dialysis fluid to facilitate the normalization of electrolyte and acid base abnormalities and the removal of low molecular weight uraemic compounds present in the plasma such as urea. The dialysis fluid is a continuously produced blend of treated tap water and a concentrated solution containing electrolytes, buffer, and glucose. The water used originates as drinking water but undergoes additional treatment. Recent surveys have indicated that the chemical and microbiological content of such water frequently fails to meet the requirements of established standards, and its bacterial content arising from the presence of a biofilm in the water distribution network or the hydraulic circuit of the dialysis machine is a contributory factor to the chronic inflammatory state in patients undergoing regular dialysis. The composition of the dialysis fluid plays an important role in the modulation of complications associated with end-stage renal disease, as well as those associated with the treatment itself. The avoidance of complications arising from water contaminants requires a constant and vigorous attention to water quality, whilst with the composition of electrolytes and buffer there is a trend towards greater individualization to provide a high degree of treatment tolerance.

Clinical waste generation from renal units: implications and solutions.

The treatment of end-stage renal disease (ESRD) makes extensive use of presterilized disposable items which, after use, are contaminated by blood. The preferred route of disposal of such items is by incineration. Disposal costs have risen and this increase in costs has not been matched by waste management programs in renal units. Many of the waste items generated also contain polyvinyl chloride (PVC) whose incineration is environmentally sensitive. Furthermore blood tubing sets contain plasticizers such as di(2-ethylhexyl) phthalate (DEHP), which is known to pose health risks to specific groups of patients. The generation of clinical waste in a dialysis unit is analyzed, issues associated with disposal are discussed, and approaches toward a cost-effective, environmentally sustainable clinical waste management program are reviewed.

Cardiovascular risk in patients with end-stage renal disease: a potential role for advanced glycation end products.

Cardiovascular complications are a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Advanced glycation end products (AGE) are elevated in the plasma of such patients and are also found in atherosclerotic plaques. The cellular signalling pathway(s) underlying AGE-induced platelet aggregation have not been elucidated. One pathway currently receiving increased attention is the externalization of the membrane phospholipid, phosphatidylserine (PS), which plays an important role in the activation of clotting factors. In this study, we have investigated ex vivo a possible link between elevated AGE concentration and PS externalization. We observed (i) increased PS externalization in platelets from patients with ESRD, (ii) reconstitution of healthy platelets with serum from patients with ESRD resulted in increased PS externalization and (iii) incubation of platelets with purified human serum albumin (HSA)-AGE elicited PS externalization suggesting a role for AGE.

The implications of water quality in hemodialysis.

Water used in dialysis requires additional treatment to minimize patient exposure to potential contaminants that may be present in drinking water. Although standards for the chemical purity of water are in existence and have eliminated many of the problems seen in renal units in the 1970s, some problems remain, and the importance of newer contaminants arising from changes in water treatment at the municipal level are being recognized. Despite this, recent surveys have indicated considerable shortcomings in compliance with chemical standards. The water quality used in the preparation of dialysis fluid also requires minimal bacterial content. Staff working in renal units are frequently unaware of the level of microbiologic contamination in their dialysis fluid arising from the presence of biofilm in the dialysis machines and the water distribution network. Bacterial fragments generated by such biofilms are able to cross the dialysis membrane and stimulate an inflammatory response in the patient. Such inflammation has been implicated in the mortality and morbidity associated with dialysis. The desire to improve treatment outcomes has led to the application of more stringent standards for the microbiologic purity of dialysis fluid and to the introduction of ultraclean dialysis fluid into clinical practice.