Optical Method and Biochemical Source for the Assessment of the Middle-Molecule Uremic Toxin ß2-Microglobulin in Spent Dialysate.

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of ß2-microglobulin (ß2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of ß2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated ß2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of ß2M were not statistically different (p > 0.35). Dialytic elimination of MM uremic toxin ß2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.

Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry.

BACKGROUND: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival. METHODS: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data. RESULTS: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and <1.5 mmol/l by center and the number of formula used per center were not associated with survival. Depending on the daily dose used, the MBD therapies were associated with survival improvement for calcium, native vitamin D, active vitamin D, sevelamer, lanthanum and cinacalcet in the second and third tertiles of dose. CONCLUSION: No influence of the dialysate calcium concentration was evidenced on survival whereas all MBD therapies were associated with a survival improvement depending on the daily dose used.

A simple method for the calculation of dialysis Kt factor as a quantitative measure of removal efficiency of uremic retention solutes: Applicability to high-dialysate vs low-dialysate volume technologies.

Dialysis urea removal metrics may not translate into proportional removal efficiency of non-urea solutes. We show that the Kt factor (plasma volume totally cleared of any solutes) differentiates removal efficiency of non-urea solutes in different technologies, and can easily be calculated by instant blood-dialysate collections. We performed mass balances of urea, creatinine, phosphorus and beta2-microglobulin by whole dialysate collection in 4 low-flux and 3 high-flux hemodialysis, 2 high-volume post-hemodiafiltration and 7 short-daily dialysis with the NxStage-One system. Instant dialysate/blood determinations were also performed at different times, and Kt was calculated as the product of the D/P ratio by volume of delivered dialysate plus UF. There were significant differences in single session and weekly Kt (whole dialysate and instant calculations) between methodologies, most notably for creatinine, phosphorus and beta2-microglobulin. Urea Kt messured in balance studies was almost equal to that derived from the usual plasma kinetic model-based Daugirdas' equation (eKt/V) and independent V calculation, indicating full correspondence. Non-urea solute Kt as a fraction of urea Kt (i.e. fractional removal relative to urea) showed significant differences between technologies, indicating non-proportional removal of non-urea solutes and urea. Instant Kt was higher than that in full balances, accounting for concentration disequilibrium between arterial and systemic blood, but measured and calculated quantitative solute removal were equal, as were qualitative Kt comparisons between technologies. Thus, we show that urea metrics may not reliably express removal efficiency of non-urea solutes, as indicated by Kt. Kt can easily be measured without whole dialysate collection, allowing to expand the metrics of dialytic efficiency to almost any non-urea solute removed by dialysis.

Influence of dialysate Ca concentrations on the therapeutic effects of etelcalcetide with concomitant drugs in patients with secondary hyperparathyroidism.

AIM: Secondary hyperparathyroidism (SHPT), a complication of haemodialysis, is commonly treated with calcimimetics. The impact of dialysates containing different calcium (Ca) concentrations on clinical efficacy of calcimimetics are unclear. We examined whether dialysate Ca concentrations influence the efficacy and dosing of etelcalcetide with concomitant drugs. METHODS: We performed post hoc analyses of a 52-week, open-label, multicentre study of etelcalcetide in Japanese SHPT patients to determine whether dialysate Ca influences the therapeutic effects of etelcalcetide with concomitant drugs. We evaluated the differences in serum intact parathyroid hormone (iPTH), corrected Ca (cCa) and phosphate levels among three dialysate Ca concentration groups (2.5, 2.75 or 3.0 mEq/L Ca). Tartrate-resistant acid phosphatase 5b (TRACP-5b) and bone alkaline phosphatase (BAP) levels were also compared. Since the dialysate Ca concentration may influence dose adjustment, we assessed the etelcalcetide and concomitant drug doses. RESULTS: There were no clinically meaningful differences in iPTH, cCa and phosphate levels among the 2.5, 2.75 and 3.0 mEq/L groups (n = 34, 64 and 35, respectively) over 52 weeks. At Week 52, more than 82%, 71% and 67% of patients had iPTH, cCa and phosphate levels within target ranges (60-240 pg/mL, 8.4-10.0 mg/dL and 3.5-6.0 mg/dL, respectively) across the three groups. TRACP-5b and BAP levels decreased by Week 52 regardless of dialysate Ca. Changes in etelcalcetide and concomitant drug doses were generally similar in each group. CONCLUSION: The efficacy and dosing of etelcalcetide with concomitant drugs were essentially unaffected by the dialysate Ca concentration. Patients showed improvements in bone hypermetabolism during treatment.

Sodium and water handling during hemodialysis: new pathophysiologic insights and management approaches for improving outcomes in end-stage kidney disease.

Space medicine and new technology such as magnetic resonance imaging of tissue sodium stores (23NaMRI) have changed our understanding of human sodium homeostasis and pathophysiology. It has become evident that body sodium comprises 3 main components. Two compartments have been traditionally recognized, namely one that is circulating and systemically active via its osmotic action, and one slowly exchangeable pool located in the bones. The third, recently described pool represents sodium stored in skin and muscle interstitium, and it is implicated in cell and biologic activities via local hypertonicity and sodium clearance mechanisms. This in-depth review provides a comprehensive view on the pathophysiology and existing knowledge gaps of systemic hemodynamic and tissue sodium accumulation in dialysis patients. Furthermore, we discuss how the combination of novel technologies to quantitate tissue salt accumulation (e.g., 23NaMRI) with devices to facilitate the precise attainment of a prescribed hemodialytic sodium mass balance (e.g., sodium and water balancing modules) will improve our therapeutic approach to sodium management in dialysis patients. While prospective studies are required, we think that these new diagnostic and sodium balancing tools will enhance our ability to pursue more personalized therapeutic interventions on sodium and water management, with the eventual goal of improving dialysis patient outcomes.

Importancia del bisfenol A, una toxina urémica de origen exógeno, en el paciente en hemodiálisis / The importance of bisphenol A, an uraemic toxin from exogenous sources, in haemodialysis patients

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Evaluation and control of microbial and chemical contamination in dialysis water plants of Italian nephrology wards.

BACKGROUND: Patients receiving haemodialysis are exposed to a large volume of dialysis fluid. The Italian Society of Nephrology (ISN) has published guidelines and microbial quality standards on dialysis water (DW) and solutions to ensure patient safety. AIM: To identify microbial and chemical hazards, and evaluate the quality of disinfection treatment in DW plants. METHODS: In 2015 and 2016, water networks and DW plants (closed loop and online monitors) of nine dialysis wards of Italian hospitals, hosting 162 dialysis beds overall, were sampled on a monthly basis to determine the parameters provided by ISN guidelines. Chlorinated drinking water was desalinated by reverse osmosis and distributed to the closed loop which feeds all online monitors. Disinfection with peracetic acid was performed in all DW plants on a monthly basis. FINDINGS: Over the 24-month study period, seven out of nine DW plants (78%) recorded negative results for all investigated parameters. Closed loop contamination with Burkholderia cepacia was detected in a DW plant from January 2015 to March 2015. Pseudomonas aeruginosa was isolated from March 2016 to May 2016 in the closed loop of another DW plant. These microbial contaminations were eradicated by shock disinfection with sodium hypochlorite and peracetic acid, followed by water flushing. CONCLUSION: These results highlight the importance of chemical and physical methods of DW disinfection. The maintenance of control measures in water plants hosted in dialysis wards ensures a microbial risk reduction for all dialysis patients.

Dendrimer-reinforced sol-gel based hollow fiber solid-phase microextraction for citalopram determination using response surface methodology.

The inclusion of a polyamidoamine dendrimer in a silica sol-gel yielded a solid nanosorbent that was used for the preconcentration, extraction, and determination of citalopram in hospital waste water, hemodialysis solution, and some drinking water. The method was developed by applying a novel nanosorbent for the solid-phase microextraction of citalopram, containing a silica sol-gel reinforced by polyamidoamine second-generation dendrimer, which was protected by a polypropylene hollow fiber. Plackett-Burman design and central composite design were utilized to evaluate the significance of several factors on the extraction efficiency. The adsorption mechanism and thermodynamic and kinetic aspects were studied. The adsorption process was exothermic and well fitted to the Bangham equation kinetic model. Under optimal conditions, the presented method was liner in the range of 0.05-100 µg/mL. The limits of detection of quantification of citalopram were 0.0095 and 0.031 µg m/L, respectively.

Is Fluorescence Valid to Monitor Removal of Protein Bound Uremic Solutes in Dialysis?

The aim of this study was to evaluate the contribution and removal dynamics of the main fluorophores during dialysis by analyzing the spent dialysate samples to prove the hypothesis whether the fluorescence of spent dialysate can be utilized for monitoring removal of any of the protein bound uremic solute. A high performance liquid chromatography system was used to separate and quantify fluorophoric solutes in the spent dialysate sampled at the start and the end of 99 dialysis sessions, including 57 hemodialysis and 42 hemodiafiltration treatments. Fluorescence was acquired at excitation 280 nm and emission 360 nm. The main fluorophores found in samples were identified as indole derivatives: tryptophan, indoxyl glucuronide, indoxyl sulfate, 5-hydroxy-indoleacetic acid, indoleacetyl glutamine, and indoleacetic acid. The highest contribution (35 ± 11%) was found to arise from indoxyl sulfate. Strong correlation between contribution values at the start and end of dialysis (R2 = 0.90) indicated to the stable contribution during the course of the dialysis. The reduction ratio of indoxyl sulfate was very close to the decrease of the total fluorescence signal of the spent dialysate (49 ± 14% vs 51 ± 13% respectively, P = 0.30, N = 99) and there was strong correlation between these reduction ratio values (R2 = 0.86). On-line fluorescence measurements were carried out to illustrate the technological possibility for real-time dialysis fluorescence monitoring reflecting the removal of the main fluorophores from blood into spent dialysate. In summary, since a predominant part of the fluorescence signal at excitation 280 nm and emission 360 nm in the spent dialysate originates from protein bound derivatives of indoles, metabolites of tryptophan and indole, the fluorescence signal at this wavelength region has high potential to be utilized for monitoring the removal of slowly dialyzed uremic toxin indoxyl sulfate.

Quantification of reactive carbonyl compounds in icodextrin-based peritoneal dialysis fluids by combined UHPLC-DAD and -MS/MS detection.

During heat sterilization of peritoneal dialysis (PD) fluids, the glucose component is partially degraded. The formed glucose degradation products impair biocompatibility and limit the long-term application of PD fluids. As an alternative to glucose, icodextrin, a polyglucose, is used as osmotic agent in PD fluids. After targeted screening for reactive carbonyl compounds, NMR- and MS-analyses very recently revealed 4-deoxyglucosone (4-DG), 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxypentosone (3,4-DDPS), and 5-hydroxymethylfurfural (5-HMF) as main polyglucose degradation products (pGDPs) in icodextrin-based PD fluids. Now, the present study established and validated a UHPLC method with DAD as well as a UHPLC-MS/MS method for the first-time quantification of those five major pGDPs in commercial icodextrin PD fluids after derivatization with o-phenylenediamine. Thus, 4-DG was identified to be the main degradation product (in concentrations up to 20 µM). In contrast to the values measured in glucose-based products, the concentration of 3-DGal (≤ 16 µM) was higher than the concentration of 3-DG (≤ 7 µM) indicating different reaction pathways starting from polyglucose compared to glucose. The compounds 3,4-DDPS and 5-HMF were present in minor quantities (≤ 0.3 µM each).

Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients.

We have previously reported that sodium is stored in skin and muscle. The amounts stored in hemodialysis (HD) patients are unknown. We determined whether (23)Na magnetic resonance imaging (sodium-MRI) allows assessment of tissue sodium and its removal in 24 HD patients and 27 age-matched healthy controls. We also studied 20 HD patients before and shortly after HD with a batch dialysis system with direct measurement of sodium in dialysate and ultrafiltrate. Age was associated with higher tissue sodium content in controls. This increase was paralleled by an age-dependent decrease of circulating levels of vascular endothelial growth factor-C (VEGF-C). Older (>60 years) HD patients showed increased sodium and water in skin and muscle and lower VEGF-C levels compared with age-matched controls. After HD, patients with low VEGF-C levels had significantly higher skin sodium content compared with patients with high VEGF-C levels (low VEGF-C: 2.3 ng/ml and skin sodium: 24.3 mmol/l; high VEGF-C: 4.1 ng/ml and skin sodium: 18.2 mmol/l). Thus, sodium-MRI quantitatively detects sodium stored in skin and muscle in humans and allows studying sodium storage reduction in ESRD patients. Age and VEGF-C-related local tissue-specific clearance mechanisms may determine the efficacy of tissue sodium removal with HD. Prospective trials on the relationship between tissue sodium content and hard end points could provide new insights into sodium homeostasis, and clarify whether increased sodium storage is a cardiovascular risk factor.

Importancia sanitaria de Pseudomonas aeruginosa en agua de hemodiálisis y su desinfección / Health importance of Pseudomonas aeruginosa in hemodyalisis water and its disinfection

Introducción: la contaminación microbiológica de los sistemas de tratamiento de agua para hemodiálisis es un problema actual, sobre todo, por la persistencia de determinados microorganismos en la formación del biofilm, entre ellos Pseudomonas aeruginosa. Objetivo: actualizar los conocimientos sobre la importancia sanitaria de Pseudomonas aeruginosa y su desinfección en agua de hemodiálisis, que aporten criterios para la toma de decisiones adecuadas. Métodos: los datos se obtuvieron de organismos internacionales como son la Asociación para el Avance de Instrumentos Médicos y la Organización Internacional de Normalización, de criterios de expertos y de resultados de laboratorio y guías de trabajo. Síntesis de la información: existen diferentes manera de actuar sobre la contaminación bacteriana, uno de ellos es evitarla, que se puede lograr si ciertos elementos del sistema son mejorados para crear finalmente un flujo turbulento y evitar la presencia de biofilm, también puede lograrse con calor o con productos químicos desinfectantes que deben estar validados. Sin embargo, para evitar la presencia de Pseudomonas aeruginosa y otros microorganismos, hay que poner énfasis en la limpieza y desinfección de forma regular y preventiva de todas las partes de los sistemas de tratamiento y de distribución de agua y de las máquinas de hemodiálisis. Conclusiones: el proceso de desinfección en el caso de contaminación por Pseudomonas aeruginosa en una planta de tratamiento es casuístico, teniendo en cuenta la diversidad de sistemas de tratamiento de agua, sistemas de distribución, su tiempo de explotación y la necesidad de tomar medidas puntuales para cada una de estos(AU)

Introduction: microbiological contamination of the hemodialysis water treatment is a present problem mainly because of the persistence of certain microorganisms in the biofilm formation, such as the case of Pseudomonas aeruginosa. Objective: to update the knowledge on the health importance of Pseudomonas aeruginosa and their disinfection in hemodialysis water for adequate decision-making. Methods: data were taken from international bodies such as the Association for the Advancement of Medical Instruments, the International Standardization Organization, expert criteria and lab results as well as work guidelines. Information synthesis: there are different ways of acting upon the bacterial contamination; one of them is to prevent it. This can be accomplished if certain elements of the system are improved to create a turbulent flow that prevents the presence of biofilm; it may also be attained by using heat or disinfectant chemical products that should be validated. However, for the purpose of preventing the presence of Pseudomonas aeruginosa and other microorganisms, emphasis must be made on regular and preventive cleaning and disinfection of all the parts of the water treatment and distribution systems and of the hemodialysis equipment. Conclusions: the process of disinfection of Pseudomonas aeruginosa in a water treatment plant is casuistic, taking into account the diversity of water treatment systems, distribution systems, operating time and need of taking point measures aimed at each of them(AU)

Importancia sanitaria de Pseudomonas aeruginosa en agua de hemodiálisis y su desinfección / Health importance of Pseudomonas aeruginosa in hemodyalisis water and its disinfection

Introducción: la contaminación microbiológica de los sistemas de tratamiento de agua para hemodiálisis es un problema actual, sobre todo, por la persistencia de determinados microorganismos en la formación del biofilm, entre ellos Pseudomonas aeruginosa. Objetivo: actualizar los conocimientos sobre la importancia sanitaria de Pseudomonas aeruginosa y su desinfección en agua de hemodiálisis, que aporten criterios para la toma de decisiones adecuadas. Métodos: los datos se obtuvieron de organismos internacionales como son la Asociación para el Avance de Instrumentos Médicos y la Organización Internacional de Normalización, de criterios de expertos y de resultados de laboratorio y guías de trabajo. Síntesis de la información: existen diferentes manera de actuar sobre la contaminación bacteriana, uno de ellos es evitarla, que se puede lograr si ciertos elementos del sistema son mejorados para crear finalmente un flujo turbulento y evitar la presencia de biofilm, también puede lograrse con calor o con productos químicos desinfectantes que deben estar validados. Sin embargo, para evitar la presencia de Pseudomonas aeruginosa y otros microorganismos, hay que poner énfasis en la limpieza y desinfección de forma regular y preventiva de todas las partes de los sistemas de tratamiento y de distribución de agua y de las máquinas de hemodiálisis. Conclusiones: el proceso de desinfección en el caso de contaminación por Pseudomonas aeruginosa en una planta de tratamiento es casuístico, teniendo en cuenta la diversidad de sistemas de tratamiento de agua, sistemas de distribución, su tiempo de explotación y la necesidad de tomar medidas puntuales para cada una de estos(AU)

Introduction: microbiological contamination of the hemodialysis water treatment is a present problem mainly because of the persistence of certain microorganisms in the biofilm formation, such as the case of Pseudomonas aeruginosa. Objective: to update the knowledge on the health importance of Pseudomonas aeruginosa and their disinfection in hemodialysis water for adequate decision-making. Methods: data were taken from international bodies such as the Association for the Advancement of Medical Instruments, the International Standardization Organization, expert criteria and lab results as well as work guidelines. Information synthesis: there are different ways of acting upon the bacterial contamination; one of them is to prevent it. This can be accomplished if certain elements of the system are improved to create a turbulent flow that prevents the presence of biofilm; it may also be attained by using heat or disinfectant chemical products that should be validated. However, for the purpose of preventing the presence of Pseudomonas aeruginosa and other microorganisms, emphasis must be made on regular and preventive cleaning and disinfection of all the parts of the water treatment and distribution systems and of the hemodialysis equipment. Conclusions: the process of disinfection of Pseudomonas aeruginosa in a water treatment plant is casuistic, taking into account the diversity of water treatment systems, distribution systems, operating time and need of taking point measures aimed at each of them(AU)

¿Cómo debe ser la hemodiafiltración en línea después del estudio ESHOL? / On-line haemodiafiltration after the ESHOL study

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Monitoring the microbiological quality of dialysate and treated water.

During hemodialysis and related therapies, removal of waste products from the blood is made possible across a semi-permeable membrane. The microbiological quality of treated water (TW) and dialysate influences a number of dialysis-related complications. This article is a review of the microbiological features of TW and dialysate fluid over a six-year period (February 2007 to December 2012) in the Dialysis Unit, 1 st Medico-Surgical Hospital, Agadir, Morocco. Installation of a water treatment unit has been followed by a protocol to check its quality periodically. Results of microbiological monitoring (microorganisms and endotoxins) were collected over a six-year period. Fifty-four samples of TW and 12 samples of dialysate fluid were analyzed for colony forming units (CFU) and endotoxin during this period. All dialysate samples were negative, while in the TW, 9.2% of the samples yielded >100/mL CFU and 16.7% yielded >0.06 EU/mL of endotoxins. These abnormal results happened especially during the first two first years. More frequent disinfection of the distribution loop was the corrective measure. To obtain high-quality water for hemodialysis, the appropriate system must be continuously monitored in order to get high microbiological quality of TW and dialysate fluid.

Effect of fluid management guided by bioimpedance spectroscopy on cardiovascular parameters in hemodialysis patients: a randomized controlled trial.

BACKGROUND: Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status. STUDY DESIGN: Prospective, randomized, and controlled study. SETTING & PARTICIPANTS: 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. INTERVENTION: Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice. OUTCOMES: The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes. MEASUREMENTS: Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months. RESULTS: Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group. LIMITATIONS: Ambulatory blood pressure data were not available for all patients. CONCLUSIONS: Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness.

Purity and stability of online-prepared hemodiafiltration fluid after storage.

BACKGROUND/AIMS: Previous studies have suggested that online hemodiafiltration (OL-HDF) fluid can be used as dialysate for continuous renal replacement therapies, and thus HDF costs can be reduced. The aims of this study were to determine the purity of OL-HDF fluid and to verify the stability of the electrolyte composition and acid-base balance during its storage. METHODS: OL-HDF fluid was collected in 70 individual bags and stored for up to 7 days. The following tests were performed daily in 10 bags: natural visible precipitation (macrocrystallization), sample collection for chemical analysis and fluid culture, limulus amebocyte lysate endotoxin test, standard culture of NALGENE® filters after passing of the fluid, and molecular analysis of bacterial DNA. RESULTS: The values of pH and pCO(2) showed a significant change starting at 24 h (p < 0.001); after 72 h, their values were beyond the measurable range. Coefficient of variation for pCO(2) was as high as 25.7%. Electrolyte composition (Na(+), K(+), Cl(-), Ca(2+) and glucose) showed a statistically significant difference over time (p < 0.05); however, their coefficients of variation were low (1.7, 1.4, 0.6, 2.3 and 0.9%, respectively), which might not be considered clinically significant. Negative results were obtained at all points by fluid and filter cultures, endotoxin test and molecular analysis. No macrocrystallization was observed at any time point. CONCLUSIONS: We demonstrate the microbiological purity of OL-HDF fluid stored for up to 7 days. The electrolyte composition was stable, except for a relevant change in pCO(2) and consequently in pH (first noted at 24 h), emphasizing the need to reassess the acid-base balance in multilayer plastic bags in future studies.

Clinical evaluation of a model for prediction of end-dialysis systemic ionized calcium concentration in citrate hemodialysis.

BACKGROUND/AIM: Citrate anticoagulation in hemodialysis (HD) is increasingly drawing attention in the nephrology community. One of the major deterrents to a more widespread use are the monitoring requirements for fear of systemic calcium derangements. Means of accurately predicting systemic ionized calcium (iCa) may help to overcome this challenge. We have previously presented a mathematical model of regional citrate anticoagulation (RCA) to address this need. Here, we present a refined model and show results in an independent validation cohort of maintenance HD patients on Citrasate®, a calcium- and citrate-containing dialysate. METHODS: A hybrid RCA model was developed, comprising the previously published 'native' RCA model and a statistical correction based on levels of alkaline phosphatase as a marker of bone turnover. The model was validated in 120 patients on Citrasate, a dialysate containing 0.8 mmol/l citrate and 1.125 mmol/l calcium. Systemic iCa was measured at the beginning and end of one HD treatment in each subject. Serum iCa predictions were compared between our previously published model and the new hybrid model. RESULTS: On average, the hybrid model predicted end-HD systemic iCa with an error (predicted - measured) of 0.028 mmol/l, compared to -0.051 mmol/l with the previously published model. There were only 4 subjects out of the 120 analyzed in whom the prediction error was <-0.1 mmol/l, and only 6 in whom the error was >+0.1 mmol/l (max: +0.13 mmol/l). CONCLUSION: This study demonstrates that the novel hybrid model is an improvement over the previously published model and that it is capable of predicting end-dialysis systemic iCa levels with improved accuracy and precision even in a citrate dialysis setting which was much different from the original derivation cohort.

Factors determining a low dose of haemodialysis as measured by ionic dialysance in critical patients with acute kidney injury.

BACKGROUND: Estimating the dialysis dose is a requirement commonly used to assess the quality of renal replacement therapy (RRT) in patients with chronic kidney disease (CKD). In patients with acute kidney injury (AKI), this value is not always evaluated and it has been estimated that the prescribed dose is seldom obtained. Reports addressing this issue in AKI individuals are scarce and most have not included an adequate number of patients or treatments, nor were patients treated with extended therapies. Kt values obtained by the ionic dialysance method have been validated for the evaluation of the dialysis dose and it has also been shown that, compared with Kt/V, this is the most sensitive strategy for revealing inadequate dialysis treatment in critically ill AKI individuals. The main aim of this study was to assess the difference between the prescribed and the administered dialysis dose in critically ill AKI patients, and to evaluate what factors determine this gap using Kt values assessed through ionic dialisance. MATERIAL AND METHOD: Data from 394 sessions of renal replacement therapy in 105 adult haemodialysis (HD) patients with oliguric acute kidney injury and admitted to ICU were included in this analysis. RRT was carried out with Fresenius 4008E dialysis machines equipped with on-line clearance monitoring (OCM® Fresenius), which use non-invasive techniques to monitor the effective ionic dialysance, equivalent to urea clearance. The baseline characteristics of the study population as well as the prescription and outcome of RRT were analysed. These variables were included in a multivariate model in which the dependent variable was the failure to obtain the threshold dose (TD). RESULTS: The main baseline characteristics of the study population/treatments were: age 66 ± 15 years, 37% female, most frequent cause of AKI: sepsis (70%). Low BP and/or vasoactive drug requirement (71%), mechanical ventilation (70%) and average individual severity index: 0.7 ± 0.26. Two hundred and one intermittent HD (IHD) and 193 extended HD (EHD) sessions were performed; the most frequently used temporary vascular access was the femoral vein catheter (79%). Prescribed Kt was 53.5 ± 14L and 21% of prescriptions fell below the TD. Sixty-one percent of treatments did not fulfill the TD (31 ± 8L) compared with 56 ± 12L obtained in the subgroup that achieved the target. Compared to IHD, EHD provided a significantly larger Kt (46 ± 16L vs 33L ± 9L). Univariate analysis showed that inadequate compliance was associated with age (>65y), male gender, intra-dialytic hypotension, low Qb, catheter line reversal, and IHD. The same variables with the exception of age and gender were independently associated in the multivariate analysis. CONCLUSIONS: The dialysis dose obtained was significantly lower than that prescribed. EHD achieved values closer to the prescribed KT and significantly higher than in IHD. Ionic Kt measurement facilitates monitoring and allows HD treatments to be extended based upon a previously established TD. Besides the chosen strategy to dispense the dose of dialysis, a well-functioning vascular access allowing for optimal blood flow and other approaches aimed at avoiding hemodynamic instability during RRT are the most important factors to achieve TD, mainly in elderly male patients. The dialysis dose should be prescribed and monitored for all critically ill AKI patients.