Cardiac arrhythmia during early-week and mid-week dialysis in hemodialysis patients.

Data on cardiac arrhythmia and electrolyte changes during the dialysis cycle have been limited. Fifty-two hemodialysis (HD) patients underwent 48-h Holter monitoring during early-week and mid-week HD sessions. Pre-HD and post-HD blood samples were collected in both HD sessions. The 48-h Holter data were divided into five phases: (1) 4-h during the early-week HD (HD1), (2) 12-h post-HD1, (3) 16-h period between Phases 2 and 4 (used as the patient's baseline electrocardiography [ECG]), (4) 12-h pre-HD2 phase, and (5) 4-h during the mid-week HD (HD2). The patients' mean age was 68.54 ± 13.37 years. We found that the dialysate-to-serum[K] gradient and changes of S[K] were significantly higher in HD1 than in HD2, as well as changes of S[Mg]. There were no significant ECG changes during the 4-h HD1 and HD2 when compared with the baseline ECG. Phase 2 of Holter ECG was the most common phase that showed significant changes (increased QT interval dispersion (QTD), increased ventricular events, increased number of premature ventricular contractions, ST elevation and ST depression), which was contributed from the dialysate[K] 2 mmol/L subgroup, but not the dialysate[K] 3 mmol/L subgroup. In the subgroup of patients with a high ultrafiltration rate (UFR; mean UFR ≥10 mL/kg/h), there were significantly increased ventricular events and ST-segment changes in Phase 2. In conclusion, ECG changes were associated with the dialysis cycle, significantly in the 12-h after early-week HD sessions. These may be associated with low dialysate[K] or high dialysate-to-S[K] gradient, high ultrafiltration rate and duration of the interdialytic interval.

Intraperitoneal vancomycin treatment of multifocal methicillin-resistant Staphylococcus aureus osteomyelitis in a patient on peritoneal dialysis.

PURPOSE: We report the case of a 2-year-old girl with end-stage renal disease managed by peritoneal dialysis (PD) who developed methicillin-resistant staphylococcal osteomyelitis of the left shoulder and was successfully treated with intraperitoneal (IP) administration of vancomycin for 2 weeks followed by oral clindamycin therapy. SUMMARY: The patient was hospitalized with tactile fever and a 3-day history of worsening fussiness. Radiography of the left shoulder showed findings indicative of osteomyelitis. Vancomycin was administered via central venous line for 3 days, during which time the patient underwent PD 24 hours a day. After magnetic resonance imaging revealed proximal humeral osteomyelitis, septic arthritis of the shoulder joint, and osteomyelitis of the scapula, the patient underwent incision and drainage of the left shoulder joint. Both blood and joint drainage cultures grew methicillin-resistant Staphylococcus aureus that was sensitive to vancomycin. The patient's central venous catheter was removed on hospital day 4; due to difficulties with peripheral i.v. access and a desire to avoid placing a peripherally inserted central venous catheter, vancomycin administration was changed to the IP route, with vancomycin added to the PD fluid. During IP treatment, serum vancomycin levels were maintained at 13.5 to 18.5 mg/L, and the calculated ratio of vancomycin area under the curve to minimum inhibitory concentration was maintained above 400. After completing a 14-day course of IP vancomycin therapy, the patient was switched to oral clindamycin, with subsequent complete resolution of osteomyelitis. CONCLUSION: IP vancomycin was effective for treatment of invasive S. aureus infection in this case. This approach should be considered in patients undergoing PD for whom peripheral i.v. access options are limited and/or not preferred.

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.

Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Relationship between dialytic parameters and reviewer confirmed arrhythmias in hemodialysis patients in the monitoring in dialysis study.

BACKGROUND: Hemodialysis patients have high rates of sudden death, but relationships between serum electrolytes, the dialysis prescription, and intra-dialytic shifts in fluid and electrolyte with arrhythmia are uncertain. METHODS: We analyzed sixty-six hemodialysis patients who underwent loop recorder implantation with continuous electrocardiographic monitoring, weekly to bi-weekly testing of pre- and post-dialysis electrolytes, and detailed capture of dialysis prescription and flow sheet data for 6 months. The incidence rate ratio (IRR) of reviewer confirmed arrhythmias (RCA) during dialysis through 8 h after dialysis and associations with serum chemistries and dialytic parameters were assessed using adjusted, negative-binomial regression. RESULTS: Among 66 individuals with a mean age of 56 years, 12,480 events were detected in 64 (97%) patients. RCA nadired 12-24 h after dialysis and increased during the final 12 h of the inter-dialytic interval through the first 8 h after dialysis. Higher pre-dialysis serum magnesium concentration was associated with lower incidence rate ratio for arrythmia (IRR per 1 mg/dL increase 0.49, 95% CI; 0.25, 0.94), as was dialysate calcium concentration > 2.5 mEq/L vs. 2.5 mEq/L (IRR 0.52, 95% CI: 0.39, 0.70). Neither intradialytic serum potassium nor weight change were significantly associated with RCA rate. However, there was effect modification such that arrhythmia rate was maximal with concurrently high intradialytic volume and potassium removal (Pinteraction = 0.01). CONCLUSIONS: Intra and post-dialytic arrhythmias are common in hemodialysis. Additional studies designed to further elucidate whether modification of the serum magnesium concentration, dialysate calcium concentration, and the extent of intradialytic potassium and fluid removal reduces the risk of per-dialytic arrhythmia are warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT01779856. Prospectively registered on January 22, 2013.

Associations between Hemodialysis Facility Practices to Manage Fluid Volume and Intradialytic Hypotension and Patient Outcomes.

BACKGROUND AND OBJECTIVES: Fluid overload and intradialytic hypotension are associated with cardiovascular events and mortality in patients on hemodialysis. We investigated associations between hemodialysis facility practices related to fluid volume and intradialytic hypotension and patient outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were analyzed from 10,250 patients in 273 facilities across 12 countries, from phase 4 of the Dialysis Outcomes and Practice Patterns Study (DOPPS; 2009-2012). Cox regression models (shared frailty) were used to estimate associations between facility practices reported by medical directors in response to the DOPPS Medical Directors Survey and all-cause and cardiovascular mortality and hospitalization, and cardiovascular events, adjusting for country, age, sex, dialysis vintage, predialysis systolic BP, cardiovascular comorbidities, diabetes, body mass index, smoking, residual kidney function, dialysis adequacy, and vascular access type. RESULTS: Of ten facility practices tested (chosen a priori), having a protocol that specifies how often to assess dry weight in most patients was associated with lower all-cause (hazard ratio [HR], 0.78; 99% confidence interval [99% CI], 0.64 to 0.94) and cardiovascular mortality (HR, 0.72; 99% CI, 0.55 to 0.95). Routine orthostatic BP measurement to assess dry weight was associated with lower all-cause hospitalization (HR, 0.86; 99% CI, 0.77 to 0.97) and cardiovascular events (HR, 0.85; 99% CI, 0.73 to 0.98). Routine use of lower dialysate temperature to limit or prevent intradialytic hypotension was associated with lower cardiovascular mortality (HR, 0.76; 99% CI, 0.58 to 0.98). Routine use of an online volume indicator to assess dry weight was associated with higher all-cause hospitalization (HR, 1.19; 99% CI, 1.02 to 1.38). Routine use of sodium modeling/profiling to limit or prevent intradialytic hypotension was associated with higher all-cause mortality (HR, 1.36; 99% CI, 1.14 to 1.63), cardiovascular mortality (HR, 1.34; 99% CI, 1.04 to 1.73), and cardiovascular events (HR, 1.21; 99% CI, 1.03 to 1.43). CONCLUSIONS: Hemodialysis facility practices relating to the management of fluid volume and intradialytic hypotension are associated with patient outcomes.

Effect of Bicarbonate-Buffered Dialysate on Ventricular Arrhythmias in Hemodialysis Patients.

BACKGROUND: The etiology of sudden cardiac death in patients with end-stage renal disease (ESRD) on hemodialysis (HD) is largely unknown, though there is evidence to suggest that metabolic alkalosis induced by HD with a high-bicarbonate dialysate/prescription may play a role. METHODS: We investigated the effects of metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate on frequency of ventricular arrhythmia in 47 patients with ESRD on chronic HD using 48-h Holter monitoring in 3 phases: intra-HD, post-HD day 1, and post-HD day 2. Serum levels of bicarbonate, calcium, and potassium along with hemodynamics were measured pre-HD, post-HD, 20-h post-HD, and 44-h post-HD. Correlations were performed to verify the association between bicarbonate prescription and change in serum bicarbonate levels post-HD and to determine if the HD-induced change in serum bicarbonate level (metabolic alkalosis) had any direct association with ambient ventricular arrhythmia (premature ventricular contractions per hour) or indirect associations with ambient ventricular arrhythmia by affecting electrolytes or hemodynamics that are known to increase the risk of ventricular arrhythmia. RESULTS: Mean pre-HD serum bicarbonate level was 21.3 mEq/L. Dialysate bicarbonate prescription (mean of 36.4 mEq/L) correlated with changes in serum bicarbonate levels immediately post-HD 26.7 mEq/L (r = 0.46, p < 0.01), 20-h post-HD 25.2 mEq/L (r = 0.38), and 44-h post-HD 23.2 mEq/L (r = 0.35, p = 0.01). No statistically significant correlations were found between the post-HD change in serum bicarbonate levels (metabolic alkalosis) with ambient ventricular arrhythmia, changes in serum calcium, potassium, or hemodynamics in any phase. CONCLUSIONS: High-bicarbonate dialysate prescription is associated with metabolic alkalosis following the HD procedure. A mild metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate solution had no direct association with ambient ventricular arrhythmia on Holter monitoring and was not associated with changes in hemodynamics or changes in serum total calcium or potassium levels. This study helps to provide guidance for the safe use of high bicarbonate dialysate/prescription in patients with ESRD on HD.

Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients.

BACKGROUND: Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis. METHODS: This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay. RESULTS: Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h-∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported. CONCLUSIONS: Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.

Dialysis Prescription and Sudden Death.

In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialysis cycle may be contributory. Some population-based observational studies have suggested that lower dialysate potassium concentrations appear to be associated with a heightened risk of postdialysis cardiac arrest in hemodialysis patients, although the optimal serum-to-dialysate potassium gradient remains unclear. Some observational studies have suggested that low dialysate calcium concentrations and high serum-to-dialysate calcium gradients may predispose patients to SCD. There is ongoing controversy about an association between higher dialysate bicarbonate concentrations and higher risk of cardiac arrest, likely owing to confounding by indication. Some observational studies also have shown that large interdialytic weight gains, fluid retention, and high ultrafiltration rates are linked with higher risk of SCD and mortality. However, there remains considerable controversy regarding the pros and cons of designating a specific upper ultrafiltration limit with extended treatment times as a clinical practice measure, and further studies are needed to define the optimal tools, metrics, targets, and implementation measures for volume control in the hemodialysis population. In this review, we highlight the epidemiology and pathophysiology of how specific aspects of the hemodialysis procedure may relate to the risk of SCD, as well as preventative strategies and future research directions that can address this risk.

Evaluation of glycemic status during the days of hemodialysis using dialysis solutions with and without glucose.

Hypoglycemia has been documented during regular hemodialysis (HD) in both diabetic and nondiabetic end-stage renal disease (ESRD) patients. The aim of this study was to evaluate the glycemic fluctuations in diabetic and nondiabetic ESRD patients during HD days using glucose-free and glucose-containing dialysate. We conducted a prospective interventional study in which 32 ESRD patients (16 diabetic and 16 nondiabetic) were included in the study. All the patients underwent two HD sessions with glucose-free bicarbonate solution (phase 1) and next two HD sessions done with 100 mg/dL glucose-containing dialysate (phase 2). Serum glucose was measured using a continuous glucose monitoring system at the 1st h, 2nd h, and 4th h in both the phases. Percentage of time above and below preset target range (70-140 mg/dL) in 24 h on HD days in both phases was noted. Glucose loss in effluent fluid from dialyzer also was estimated at the 1st h, 2nd h, and 4th h. Statistical analysis was performed using Statistical Package for the Social Sciences software. Data are expressed as mean ± standard deviation. The Chi-square test was used for comparison of categorical variables. Continuous variables were compared using Student's t-test. Value of P <0.05 was considered statistically significant. With glucose-free dialysate solution, 20 patients (diabetic - 15, nondiabetic - 5) had 22 episodes of hypoglycemia in 64 sessions and with glucose-containing solution, only five patients (diabetic - 4, nondiabetic - 1) had five episodes of hypoglycemia (P = 0.002). For all patients, glucose lost (g/h) in the effluent fluid was at lower values in phase 2 (5.91 ± 1.5) when compared to phase 1 (7.08 ± 10.9) (P <0.0002). This was also observed both among the diabetic and nondiabetic patients. The mean percentage of time below target out of 24 h on HD days in phase 1 was significantly higher as against phase 2 (33% vs. 18.7%; P = 0.0001) which was observed both among diabetic group (18.65% vs. 13.5%; P = 0.03) and nondiabetic group (48.12 % vs. 23.4%; P = 0.0003); the mean percentage of time above the target (>140 mg/dL) out of 24 h on HD days was significantly higher than phase 2 (21.1% vs. 9.3%; P = 0.0001). This was also observed among diabetics group of patients (18.8% vs. 8.6 %; P = 0.0001). Most of this time above target occurred during the post HD period. However, in the nondiabetic group, there was no significant difference between the two phases. Glucose-containing dialysate at 100 mg/dL significantly reduced the hypoglycemic episodes and also the intensity of hypoglycemia. Diabetic patients dialyzed with glucose-free dialysate had increased time above target (akin to Somogyi effect) in the post HD period compared to same patients dialyzed with glucose-containing dialysate. Hence, glucose-containing dialysate appears to offer better glycemic control and lesser glycemic fluctuations during HD days for both diabetic and nondiabetic ESRD patients.

Routine hemodialysis induces a decline in plasma magnesium concentration in most patients: a prospective observational cohort study.

In hemodialysis patients, lower plasma magnesium (Mg) concentrations are associated with a higher overall and cardiovascular mortality. The optimal concentration appears to be above the reference range for the healthy population. Plasma Mg is not routinely measured after hemodialysis. Aim of this study was to determine the effect of routine hemodialysis on plasma Mg. Plasma Mg was measured in duplicate before (Mgpre) and after (Mgpost) dialysis in 6 consecutive hemodialysis sessions of 34 patients using a fixed 0.50 mmol/L dialysate Mg concentration. Mean Mgpre was 0.88 mmol/L (±0.14) and mean Mgpost was statistically significantly lower: mean intra-dialytic decline 0.10 mmol/L (95%-CI 0.06-0.13). A 0.10 mmol/L higher Mgpre was associated with a 0.03 mmol/L higher Mgpost (95%-CI 0.024-0.037). At a Mgpre of 0.74 mmol/L, Mgpost equalled Mgpre. There was an intra-dialytic decline of plasma Mg at higher Mgpre values and an increase at lower Mgpre values. In conclusion, in the majority of the hemodialysis patients, Mgpre concentrations are in the reference range of the healthy population, which may be too low for hemodialysis patients. Routine hemodialysis with the widely used 0.50 mmol/L dialysate Mg concentration, further declines magnesium in the majority of patients. Current dialysate Mg concentrations may be too low.

Intermittent Infusion Hemodiafiltration: The Principle and Its Clinical Application.

The present study aimed to propose a new hemodiafiltration (HDF) method (intermittent infusion HDF) that repeats intermittent infusion during hemodialysis to temporarily enhance peripheral circulation and improves solute removal efficiency through (a) correcting blood distribution (increase in effective vascular surface area), (b) stirring body fluids, and (c) promoting solute removal and examining its clinical effects.

Una nueva generación de triacetato de celulosa adecuado para hemodiafiltración on-line / A new generation of cellulose triacetate suitable for online haemodiafiltration

Antecedentes: La hemodiafiltración on-line (HDF-OL) es actualmente la técnica de hemodiálisis (HD) más efectiva y aumenta la supervivencia. Hasta el momento presente las membranas de alta permeabilidad con baja pérdida de albúmina como las de polisulfona, poliamida y poliacrilonitrilo son las más utilizadas. Las membranas de triacetato de celulosa (TAC), limitadas inicialmente para su uso en HDF-OL, han evolucionado. El objetivo del estudio fue determinar si las membranas de nueva generación de TAC asimétrico (TACA) son más adecuadas para realizar alto transporte convectivo. Pacientes y métodos: Se estudiaron 16 pacientes, 10 hombres y 6 mujeres, en programa de HDF-OL. A cada paciente se le realizaron 4 sesiones diferentes, con HD o HDF-OL, o con filtros de TAC o TACA de 1,9 m2, aleatorizando el orden. En cada sesión se determinaron concentración de urea, creatinina, β2-microglobulina, mioglobina, prolactina, α1-microglobulina, α1-glicoproteína ácida y albúmina en suero al inicio y al final de cada sesión, para calcular el porcentaje de reducción. Así mismo, se cuantificó la pérdida de solutos y albúmina en el líquido de diálisis. Resultados: Con las membranas de TACA se consiguió un volumen de sustitución en HDF-OL significativamente superior a las membranas de TAC clásicas (32,1±3,1 vs. 19,7±4,5L; p<0,001). En términos de depuración, la eliminación de moléculas pequeñas fue similar con ambas membranas, pero, en moléculas grandes, con HDF-OL la depuración fue mayor con TACA. En HDF-OL, el porcentaje de reducción de la β2-microglobulina se incrementó un 29%, un 27,7% la mioglobina, un 19,5% la prolactina, un 49% la α1-microglobulina, y se duplicó la α1-glicoproteína ácida (p<0,01 en todas las situaciones). La pérdida de albúmina fue inferior a 2 g en todas las situaciones de estudio. Conclusión: Las membranas de TAC de nueva generación han demostrado ser eficaces para alcanzar los objetivos de HDF-OL, sin que haya una mayor pérdida de albúmina (AU)

Background: Online haemodiafiltration (OL-HDF) is currently the most effective dialysis technique that also improves survival. To date, high permeability membranes with low albumin loss, such as polysulfone, polyamide and polyacrylonitrile membranes have been the most widely used. However, the initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has expanded. The aim of the study was to ascertain whether the latest generation asymmetric CTA membranes are more effective in obtaining high convective transport. Patients and methods: A total of 16 patients (10 males and 6 females) undergoing OL-HDF were studied. Each patient underwent 4 different sessions, with haemodialysis or OL-HDF, and/or with CTA or asymmetric CTA 1.9 m2 membranes. Each session was assigned in a randomised order. Serum levels of urea, creatinine, β2-microglobulin, myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein and albumin where measured at the beginning and end of each session to obtain the reduction rate. The loss of solutes and albumin was quantified from the dialysate. Results: A significantly greater replacement volume in OL-HDF (32.1±3.1 vs. 19.7±4.5 l, P<.001) was obtained by using asymmetrical CTA membranes compared to conventional CTA membranes. Regarding uraemic toxin removal, both membranes obtained similar results for small molecules, whereas asymmetric CTA membranes achieved better results for large molecules, increasing the reduction ratio by 29% for β2-microglobulin, 27.7% for myoglobin, 19.5% for prolactin, 49% for α1-microglobulin and double for α1-acid glycoprotein (P<0.001 in all situations). The loss of albumin was less than 2g for all treatment sessions. Conclusion: Latest-generation asymmetric CTA have proven to be effective in attaining OL-HDF objectives without increased albumin loss (AU)

Prescription and Delivery of the Right Continuous Renal Replacement Therapies Dose.

This chapter focuses on the definitions and impact of prescription and delivery of the right dose of treatment in patients on continuous renal replacement therapy (CRRT). We define "dose" and the concepts of efficiency, intensity, and efficacy; differentiate their multiple components; and describe the practical application of those concepts to direct patient care. In the article, we emphasize the effects of delivered dose variation on solute control, and list the main factors affecting CRRT dose delivery. Finally, we summarize the main indicators of dose monitoring and emphasize the importance of an excellent quality control system to ensure appropriate delivery of care to critically ill patients with acute kidney injury.

Continuous Renal Replacement Therapy Quality Control and Performance Measures.

Continuous renal replacement therapy (CRRT) is one of the most predominant forms of renal replacement therapy (RRT) currently in use now, this therapy being the initial RRT modality in most critically ill patients. However, in general, the quality of CRRT is still suboptimal. The quality of CRRT is affected by many factors, including the optimal prescription and precision delivery, the CRRT providers' professional level, and the CRRT device used. Establishment of a comprehensive quality control system covering all the aspects and procedures of CRRT is essential. Quality measures for structure, process, and outcome of CRRT need to be developed, evaluated, and implemented to ensure the high quality of CRRT. Some CRRT quality improvement methods such as the professional education and specialized team and the application of citrate anticoagulation to extend filter lifespan have been found to be potentially beneficial but need further validation. After all, much work is needed in this field because of the heterogeneity in CRRT practice. More evidence is needed to improve the CRRT quality control system. These are challenges that will need to be addressed in the future.

Dialysate temperature of 36 °C: association with clinical outcomes.

Dialysate cooling, either individualized based upon patient body temperature, or to a standardized temperature below 37 °C, has been proposed to minimize hemodynamic insults and improve outcomes among hemodialysis patients. However, low dialysate temperatures (35-35.5 °C) are associated with patient discomfort, and individualized dialysate cooling is difficult to operationalize. Here, we tested whether a standardized dialysate temperature of 36 °C (dT36) was associated with improved clinical outcomes compared to the default temperature of 37 °C (dT37). Because patients with known hemodynamic instability may be selectively prescribed dT36, we minimized selection bias by considering only incident adult in-center hemodialysis patients who, between Jan 2011 and Dec 2013 received their first-ever hemodialysis treatment at a large dialysis organization. Exposure status was based on the treatment order for this first-ever treatment. 313 dT36 patients were identified and propensity-score matched (1:5) to 1565 dT37 controls. Death, hospitalization, and missed hemodialysis treatments were considered from the date of first-ever hemodialysis treatment until the earliest of death, loss to follow-up, crossover (month in which prescribed dialysate temperature was consistent with patient's exposure group for <80% of treatments), or study end (June 2015). During follow-up, rates of death, hospitalization and missed hemodialysis treatments did not differ between the two groups. This study therefor showed no benefit of dT36 vs. dT37 with respect to these clinical outcomes. Our results do not favor conversion to a default dialysate temperature of 36 °C. Individualized dialysate cooling may provide a more reliable approach to achieve the hemodynamic benefits associated with reduced dialysate temperature.

Reduced Mortality in Maintenance Haemodialysis Patients on High versus Low Dialysate Magnesium: A Pilot Study.

BACKGROUND: Although low magnesium levels have been associated with an increased mortality in dialysis patients, they are kept low by routinely-used dialysates containing 0.50 mmol/L magnesium. Thus, we investigated the impact of a higher dialysate magnesium concentration on mortality. METHODS: 25 patients on high dialysate magnesium (HDM) of 0.75 mmol/L were 1:2 matched to 50 patients on low dialysate magnesium (LDM) of 0.50 mmol/L and followed up for 3 years with regards to all-cause and cardiovascular mortality. Patients were matched according to age, gender, a modified version of the Charlson Comorbidity Index (CCI), and smoking status. RESULTS: During the follow-up period, five patients died in the HDM and 18 patients in the LDM group. Patients in the HDM group had significantly higher ionized serum magnesium levels than matched controls (0.64 ± 0.12 mmol/L vs. 0.57 ± 0.10 mmol/L, p = 0.034). Log rank test showed no difference between treatment groups for all-cause mortality. After adjustment for age and CCI, Cox proportional hazards regression showed that HDM independently predicted a 65% risk reduction for all-cause mortality (hazard ratio 0.35, 95% confidence interval [CI]: 0.13, 0.97). Estimated 3-year probability of death from a cardiovascular event was 14.5% (95% CI: 7.9, 25.8) in the LDM group vs. 0% in the HDM group. Log rank test found a significant group difference for cardiovascular mortality (χ2 = 4.15, p = 0.042). CONCLUSIONS: Our data suggests that there might be a beneficial effect of an increased dialysate magnesium on cardiovascular mortality in chronic dialysis patients.

Cross-linked Polyelectrolyte and Its Function in Adsorption of Fluid and Excess Nitrogen Waste Products: an Experimental Study on Dialysate Effluent Fluid.

INTRODUCTION: One of the most important issues in patients with chronic kidney disease is fluid retention and volume overload accompanied by retention of nitrogenous waste products and some electrolytes. Bowel fluid contains high levels of urea, creatinine, uric acid, and electrolytes, which make it a potential candidate for intestinal excretion of nitrogen wastes and electrolytes. Cross-linked polyelectrolyte (CLP) is a polymer that, given orally, absorbs excess fluid, electrolyte, and nitrogenous waste products. MATERIALS AND METHODS: In an experimental study on 30 hemodialysis patients, the effect of CLP on adsorption of fluid, urea, creatinine, uric acid, sodium, and potassium were evaluated. For this purpose, 500 mL of effluent fluid of each patient were collected at the 1st hour of dialysis. The concentrations of the abovementioned products were measured by standard methods. Then the dialysate effluent samples were treated with 6 g of CLP and incubated for 4 hours at 37°C. RESULTS: Up to 80% of effluent fluid water was adsorbed by CLP. There were significant reductions in urea, creatinine, uric acid, and sodium levels in the remaining effluent fluid (P < .001). In contrast, the amount of potassium increased in the effluent fluid. CONCLUSIONS: Using CLP in addition to functional medical super adsorbents can be a possible adequate substitute for conventional dialysis methods, especially hemodialysis.

The dynamics of the metabolism of acetate and bicarbonate associated with use of hemodialysates in the ABChD trial: a phase IV, prospective, single center, single blind, randomized, cross-over, two week investigation.

BACKGROUND: In the United States, hemodialysis (HD) is generally performed via a bicarbonate dialysate. It is not known if small amounts of acid used in dialysate to buffer the bicarbonate can meaningfully contribute to overall buffering administered during HD. We aimed to investigate the metabolism of acetate with use of two different acid buffer concentrates and determine if it effects blood bicarbonate concentrations in HD patients. METHODS: The Acid-Base Composition with use of hemoDialysates (ABChD) trial was a Phase IV, prospective, single blind, randomized, cross-over, 2 week investigation of peridialytic dynamics of acetate and bicarbonate associated with use of acid buffer concentrates. Eleven prevalent HD patients participated from November 2014 to February 2015. Patients received two HD treatments, with NaturaLyte® and GranuFlo® acid concentrates containing 4 and 8 mEq/L of acetate, respectively. Dialysate order was chosen in a random fashion. The endpoint was to characterize the dynamics of acetate received and metabolized during hemodialysis, and how it effects overall bicarbonate concentrations in the blood and dialysate. Acetate and bicarbonate concentrations were assessed before, at 8 time points during, and 6 time points after the completion of HD. RESULTS: Data from 20 HD treatments for 11 patients (10 NaturaLyte® and 10 GranuFlo®) was analyzed. Cumulative trajectories of arterialized acetate were unique between NaturaLyte® and GranuFlo® (p = 0.003), yet individual time points demonstrated overlap without remarkable differences. Arterialized and venous blood bicarbonate concentrations were similar at HD initiation, but by 240 min into dialysis, mean arterialized bicarbonate concentrations were 30.2 (SD ± 4.16) mEq/L in GranuFlo® and 28.8 (SD ± 4.26) mEq/L in NaturaLyte®. Regardless of acid buffer concentrate, arterial blood bicarbonate was primarily dictated by the prescribed bicarbonate level. Subjects tolerated HD with both acid buffer concentrates without experiencing any related adverse events. CONCLUSIONS: A small fraction of acetate was delivered to HD patients with use of NaturaLyte® and GranuFlo® acid buffers; the majority of acetate received was observed to be rapidly metabolized and cleared from the circulation. Blood bicarbonate concentrations appear to be determined mainly by the prescribed concentration of bicarbonate. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov on 11 Dec 2014 ( NCT02334267 ).

Three-Stream, Bicarbonate-Based Hemodialysis Solution Delivery System Revisited: With an Emphasis on Some Aspects of Acid-Base Principles.

Hemodialysis patients can acquire buffer base (i.e., bicarbonate and buffer base equivalents of certain organic anions) from the acid and base concentrates of a three-stream, dual-concentrate, bicarbonate-based, dialysis solution delivery machine. The differences between dialysis fluid concentrate systems containing acetic acid versus sodium diacetate in the amount of potential buffering power were reviewed. Any organic anion such as acetate, citrate, or lactate (unless when combined with hydrogen) delivered to the body has the potential of being converted to bicarbonate. The prescribing physician aware of the role that organic anions in the concentrates can play in providing buffering power to the final dialysis fluid, will have a better knowledge of the amount of bicarbonate and bicarbonate precursors delivered to the patient.