Dialysate Bicarbonate Concentration Research Articles

Hemodynamic effects of low versus high dialysate bicarbonate concentration in hemodialysis patients.

Hemodialysis treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with hemodynamic instability. The aim of this study was to perform a detailed comparison of high and low dialysate bicarbonate in terms of blood pressure, intradialytic hemodynamic parameters, orthostatic blood pressure, and electrolytes. Fifteen hemodialysis patients were examined in a single-blind, randomized, controlled, crossover study. Participants underwent a 4-h hemodialysis session with dialysate bicarbonate concentration of 30 or 38 mmol/L with 1 week between interventions. Blood pressure was monitored throughout hemodialysis, while cardiac output, total peripheral resistance, stroke volume, and central blood volume were assessed with ultrasound dilution technique (Transonic). Orthostatic blood pressure was measured pre- and post-hemodialysis. With similar ultrafiltration (UF) volume (2.6 L), systolic blood pressure (SBP) tended to decrease more during high dialysate bicarbonate compared to low dialysate bicarbonate; the mean (95% confidence interval) between treatment differences in SBP were: 8 (-4; 20) mmHg (end of hemodialysis) and 7 (0; 15) mmHg (post-hemodialysis). Stroke volume decreased whereas total peripheral resistance increased significantly more during high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment differences: Stroke volume: 12 (1; 23) mL; Total peripheral resistance: -2.9 (-5.3; -0.5) mmHg/(L/min). Cardiac output tended to decrease more with high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment difference 0.7 (0.0; 1.4) L/min. High dialysate bicarbonate caused alkalosis, hypocalcemia, and lower plasma potassium, whereas patients remained normocalcemic with normal pH during low dialysate bicarbonate. Orthostatic blood pressure response after dialysis did not differ significantly. The use of high dialysate bicarbonate compared to low dialysate bicarbonate was associated with hypocalcemia, alkalosis, and a more pronounced hypokalemia. During hemodialysis with UF, a better preservation of blood pressure, stroke volume, and cardiac output may be achieved with low dialysate bicarbonate compared to high dialysate bicarbonate.

#1328 Haemodynamic effects of low versus high dialysate bicarbonate concentration in haemodialysis patients

Abstract Background and Aims Haemodialysis (HD) treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with haemodynamic instability. We performed a detailed comparison of blood pressure (BP), haemodynamic parameters, electrolytes and orthostatic BP response with low (LDB) versus high dialysate bicarbonate concentration (HDB). Method Fifteen HD patients were examined in a single-blind, randomised, controlled, crossover study. Participants underwent a 4-hour HD session with dialysate bicarbonate concentration of 30 mmol/l (LDB) or 38 mmol/l (HDB) with one week between interventions. During HD, cardiac output (CO), total peripheral resistance (TPR), stroke volume (SV) and central blood volume were measured with ultrasound dilution technique (Transonic). Throughout dialysis, blood samples were obtained from the arterial cannula. Orthostatic BP was measured pre and post HD. Results With similar ultrafiltration volume (2.6 litres), systolic BP tended to decrease more during HDB compared to LDB (Fig. 1 and Table 1); the mean (95% confidence interval) between treatment differences in systolic BP were: 8 (-4;20) mmHg (end of HD) and 7 (0;15) mmHg (post HD). SV decreased (Fig. 2) whereas TPR increased significantly more during HDB compared to LDB with mean between treatment differences: SV: 12 (1;23) ml; TPR: -2.9 (-5.3;-0.5) mmHg/(L/min). CO tended to decrease more with HDB compared to LDB with mean between treatment difference 0.7 (0.0;1.4) L/min. HDB caused alkalosis, hypocalcaemia and lower plasma potassium, whereas patients remained normocalcaemic with normal pH during LDB (Table 1). Orthostatic BP response after dialysis did not differ significantly. Conclusion HDB compared to LDB was associated with hypocalcaemia and alkalosis and a more pronounced hypokalaemia which may impair preservation of BP, SV and CO during HD.

Effect of time-dependent dialysate bicarbonate concentrations on acid–base and uremic solute kinetics during hemodialysis treatments

Recent studies have suggested benefits for time-dependent dialysate bicarbonate concentrations (Dbic) during hemodialysis (HD). In this clinical trial, we compared for the first time in the same HD patients the effects of time-dependent changes with constant Dbic on acid–base and uremic solute kinetics. Blood acid–base and uremic solute concentration were measured in twenty chronic HD patients during 4-h treatments with A) constant Dbic of 35 mmol/L; B) Dbic of 35 mmol/L then 30 mmol/L; and C) Dbic of 30 mmol/L then 35 mmol/L (change of Dbic after two hours during Treatments B and C). Arterial blood samples were obtained predialysis, every hour during HD and one hour after HD, during second and third treatments of the week with each Dbic concentration profile. Blood bicarbonate concentration (blood [HCO3]) during Treatment C was lower only during the first three HD hours than in Treatment A. Overall blood [HCO3] was reduced during Treatment B in comparison to Treatment A at each time points. We conclude that a single change Dbic in the middle of HD can alter the rate of change in blood [HCO3] and pH during HD; time-dependent Dbic had no influence on uremic solute kinetics.

Association Between the Dialysate Bicarbonate and the Pre-dialysis Serum Bicarbonate Concentration in Maintenance Hemodialysis: A Retrospective Cohort Study.

It is unclear whether the use of higher dialysate bicarbonate concentrations is associated with clinically relevant changes in the pre-dialysis serum bicarbonate concentration. The objective is to examine the association between the dialysate bicarbonate prescription and the pre-dialysis serum bicarbonate concentration. This is a retrospective cohort study. The study was performed using linked administrative health care databases in Ontario, Canada. Prevalent adults receiving maintenance in-center hemodialysis as of April 1, 2020 (n = 5414) were included. Patients were grouped into the following dialysate bicarbonate categories at the dialysis center-level: individualized (adjustment based on pre-dialysis serum bicarbonate concentration) or standardized (>90% of patients received the same dialysate bicarbonate concentration). The standardized category was stratified by concentration: 35, 36 to 37, and ≥38 mmol/L. The primary outcome was the mean outpatient pre-dialysis serum bicarbonate concentration at the patient level. We examined the association between dialysate bicarbonate category and pre-dialysis serum bicarbonate using an adjusted linear mixed model. All dialysate bicarbonate categories had a mean pre-dialysis serum bicarbonate concentration within the normal range. In the individualized category, 91% achieved a pre-dialysis serum bicarbonate ≥22 mmol/L, compared to 87% in the standardized category. Patients in the standardized category tended to have a serum bicarbonate that was 0.25 (95% confidence interval [CI] = -0.93, 0.43) mmol/L lower than patients in the individualized category. Relative to patients in the 35 mmol/L category, patients in the 36 to 37 and ≥38 mmol/L categories tended to have a serum bicarbonate that was 0.70 (95% CI = -0.30, 1.70) mmol/L and 0.87 (95% CI = 0.14, 1.60) mmol/L higher, respectively. There was no effect modification by age, sex, or history of chronic lung disease. We could not directly confirm that all laboratory measurements were pre-dialysis. Data on prescribed dialysate bicarbonate concentrations for individual dialysis sessions were not available, which may have led to some misclassification, and adherence to a practice of individualization could not be measured. Residual confounding is possible. We found no significant difference in the pre-dialysis serum bicarbonate concentration irrespective of whether an individualized or standardized dialysate bicarbonate was used. Dialysate bicarbonate concentrations ≥38 mmol/L (vs 35 mmol/L) may increase the pre-dialysis serum bicarbonate concentration by 0.9 mmol/L.

Effects of Oral Sodium Bicarbonate Supplementation on Protein Metabolism and Inflammation in Iraqi Hemodialysis Patients: An Open-Label Randomized Controlled Trial.

The effect of correcting metabolic acidosis on protein metabolism in hemodialysis patients is controversial. To study the effects of oral sodium bicarbonate on protein metabolism and markers of inflammation in acidotic hemodialysis patients. Patients and Methods. An open-label randomized controlled trial was conducted at a single center. Sixty-six clinically stable adult hemodialysis patients were recruited with an average predialysis serum bicarbonate level of <22 mmol/l and a dialysate bicarbonate concentration of 35 mmol/l. Forty-nine participants have completed the study. Oral sodium bicarbonate tablets of 500 mg were given daily in the intervention group (n = 25) for 12 weeks versus the standard of care in the control group (n = 24). Outcomes compared intervention versus nonintervention in both groups at equivalent time points (0 and 3 months). The clinical data, anthropometry, dialysis adequacy, albumin, normalized protein catabolism rate, blood gas analysis, and bicarbonate were recorded at 0 and 3 months. In addition, muscle mass and handgrip strength were measured. Finally, IL-6 as a marker of inflammation was measured at randomization and three months. Serum bicarbonate and pH increased significantly from 17.57 ± 3.34 mmol/L to 20.69 ± 2.54 mmol/L and from 7.26 ± 0.06 to 7.34 ± 0.04, respectively (p < 0.0001). Serum albumin was significantly higher in the intervention group at three months than in the control group, 4.11 ± 0.45 vs. 3.79 ± 0.47 (p value 0.011). Serum potassium significantly decreased in the intervention group at three months compared to the control group, 5.00 ± 0.43 mEq/l vs. 5.33 ± 0.63 mEq/l (p value 0.03). Muscle strength expressed as handgrip has improved significantly in the intervention group at three months compared to the control group, 45.01 ± 19.19 vs. 33.93 ± 15.06 (p value 0.03). The IL-6 values were less in the intervention group at 3 months with a p value of 0.01. The interdialytic weight of the intervention group at three months was 2.42 ± 0.64 compared to the 2.20 ± 1.14 control group, but this did not reach statistical significance (p value of 0.4). The composite of (albumin + nPCR) at three months was achieved in 59.18% of the intervention group compared to 14.28% with a p value of 0.01. Correcting metabolic acidosis in hemodialysis patients improved serum albumin and nPCR without hypokalemia or significant interdialytic weight gain. This was particularly evident in patients with minimal inflammation with low IL-6 values.

Validity of the hydrogen ion mobilisation model during haemodialysis with time-dependent dialysate bicarbonate concentrations.

The hydrogen ion (H+) mobilisation model has been previously shown to accurately describe blood bicarbonate (HCO3) kinetics during haemodialysis (HD) when the dialysate bicarbonate concentration ([HCO3]) is constant throughout the treatment. This study evaluated the ability of the H+ mobilization model to describe blood HCO3 kinetics during HD treatments with a time-dependent dialysate [HCO3]. Data from a recent clinical study where blood [HCO3] was measured at the beginning of and every hour during 4-h treatments in 20 chronic, thrice-weekly HD patients with a constant (Treatment A), decreasing (Treatment B) and increasing (Treatment C) dialysate [HCO3] were evaluated. The H+ mobilization model was used to determine the model parameter (Hm) that provided the best fit of the model to the clinical data using nonlinear regression. A total of 114 HD treatments provided individual estimates of Hm. Mean ± standard deviation estimates of Hm during Treatments A, B and C were 0.153 ± 0.069, 0.180 ± 0.109 and 0.205 ± 0.141 L/min (medians [interquartile ranges] were 0.145 [0.118,0.191], 0.159 [0.112,0.209], 0.169 [0.115,0.236] L/min), respectively; these estimates were not different from each other (p = 0.26). The sum of squared differences between the measured blood [HCO3] and that predicted by the model were not different during Treatments A, B and C (p = 0.50), suggesting a similar degree of model fit to the data. This study supports the validity of the H+ mobilization model to describe intradialysis blood HCO3 kinetics during HD with a constant Hm value when using a time-dependent dialysate [HCO3].

Relationship between Dialysate Bicarbonate Concentration and All-Cause Mortality in Hemodialysis Patients

Introduction: The optimal dialysate bicarbonate concentration (DBIC) for hemodialysis (HD) remains controversial. Herein, we analyzed the effect of dialysate bicarbonate levels on mortality in HD patients. Methods: Patients undergoing maintenance HD were recruited from the HD unit of the Daping Hospital. Patients were categorized into quartiles according to their DBIC level (quartile 1: <31.25 mmol/L, n = 77; quartile 2: 31.25–32.31 mmol/L, n = 76; quartile 3: 32.31–33.6 mmol/L; n = 81; quartile 4: ≥33.6 mmol/L, n = 79). Demographic and clinical data were collected. Survival curves were estimated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to estimate the association between DBIC and all-cause mortality. Results: We included 313 patients undergoing maintenance HD with a mean DBIC of 32.16 ± 1.59 mmol/L (range, 27.20–34.72 mmol/L). The patients in quartile 4 were more likely to have higher pre- and post-HD serum bicarbonate concentrations than those in other quartiles. The mortality rate was lowest in quartile 2 (10.53%). The survival time was significantly lower in the quartile 4 group than in the other quartiles (p = 0. 008, log-rank test). After full adjustment, the hazard ratio (per 3 mmol/L higher DBIC) for all-cause mortality was 4.29 (95% confidence interval, 2.11–8.47) in all patients, whereas no significant association was observed between DBIC and initial hospitalization. Conclusions: Our data indicate that DBIC is positively associated with all-cause mortality. A DBIC concentration of 31–32 mmol/L may benefit patient outcomes. This study provides an evidence-based medical basis for optimal dialysis prescription in the future.

Tailoring the dialysate bicarbonate eliminates pre-dialysis acidosis and post-dialysis alkalosis.

ABSTRACTBackgroundBoth metabolic acidosis and alkalosis increase hospitalizations, haemodynamic instability and mortality in haemodialysis patients. Unfortunately, current practices opt for a one-size-fits-all approach, leaving many patients either acidotic before or alkalotic after dialysis sessions. Therefore an individualized adjustment of these patients’ dialysate bicarbonate prescriptions could reduce these acid–base imbalances.MethodsThis is a prospective single-cohort study of patients on a chronic haemodiafiltration programme. The dialysate bicarbonate prescription was modified according to the pre- and post-dialysis total carbon dioxide (TCO2) values of 19–25 mEq/L and ≤29 mEq/L, respectively, with an adjustment formula calculated with the data obtained from previously published work by our group. In addition, we analysed this adjustment's effect on plasma sodium, potassium, phosphorus, parathyroid hormone (PTH) and calcium.ResultsAt baseline, only 67.9% of patients were within the desired pre- and post-dialysis TCO2 target range. As of the first month, every followed patient met the TCO2 target range objective in pre-dialysis measurements and ˃95% met the post-dialysis TCO2 target. At the end of the study, 75% of the patients were on dialysate bicarbonate of 32–34 mEq/L. There were no clinically significant changes in calcium, phosphate, PTH, sodium or potassium levels. Also, we did not notice any increase in intradialytic adverse events.ConclusionsWe suggest an individualized adjustment of the dialysate bicarbonate concentration according to the pre- and post-dialysis TCO2 values. With it, nearly every patient in our cohort reached the established range, potentially reducing their mortality risk.

MO658: Effect of a Time-Dependent Dialysate Bicarbonate Concentration on Intradialytic and Postdialytic Blood Bicarbonate Kinetics

Abstract BACKGROUND AND AIMS Use of a high dialysate bicarbonate (HCO3) concentration during haemodialysis (HD) is associated with higher patient mortality, potentially due to post-dialytic metabolic alkalosis [1]; it remains unclear how to optimize dialysate HCO3 concentration ([HCO3]) to both neutralize interdialytic acid generation and minimize post-dialytic alkalosis. We compared the effects of an intradialytic increasing or decreasing dialysate [HCO3] during HD on blood bicarbonate kinetics. METHOD Blood [HCO3] was measured in 11 chronic, thrice-weekly HD patients (5 male, 6 female) during 4-h treatments with i) constant dialysate [HCO3] of 35 mEq/L; ii) dialysate [HCO3] of 35 mEq/L for the first 2-h and 30 mEq/L for the second 2-h; and iii) dialysate [HCO3] of 30 mEq/L for the first 2-h and 35 mEq/L for the second 2-h. Treatment interventions were fixed during a given week, and arterial blood samples were obtained at the start of treatment, every hour during the treatment and 1-h after the treatment during the second and third treatments of the week; a total of 66 HD treatments were monitored. Blood acid-base composition was determined using a blood gas analyzer; [HCO3] was calculated from measured pH and partial pressure of carbon dioxide using the Henderson–Hasselbalch equation. Blood [HCO3] for each patient was averaged over the second and third treatment of the week. HCO3 transfer from dialysate to blood was calculated by numerical integration of the time-dependence of the blood bicarbonate profile assuming a constant dialyzer dialysate of 198 mL/min. Blood flow rates were 250–350 mL/min and were relatively constant for each patient; dialysate flow rates were always 500 mL/min. RESULTS Pre- and post-dialytic body weights were 71.1 ± 12.6 kg and 69.5 ± 12.1 kg [mean ± standard deviation (SD)], respectively, during the first study treatment. Mean values of blood [HCO3] are shown in the Figure; certain statistics are tabulated. Blood pH at the start of treatment was not different (P = 0.12) between Treatments A and B (7.41 versus 7.40, respectively) but was lower (P &amp;lt; .001) at end of treatment during Treatment B than A (7.47 versus 7.51). HCO3 transfer from the dialysate to blood during A, B and C treatments were 140 ± 58, 97 ± 47 and 120 ± 47 mEq, respectively. HCO3 transfer trended lower (P = .09) during treatment B than A. CONCLUSION HD treatments with a dialysate [HCO3] of 35 mEq/L for only the first 2-h led to a reduction in HCO3 transfer to the patient and lower post-dialytic blood [HCO3] and pH. Lowering dialysate [HCO3] after 2-h of a 4-h HD treatment can reduce post-dialytic metabolic alkalosis. Further, long-term studies with such a strategy are needed to evaluate its effect on patient outcomes.

MO656: Validity of the Hydrogen Ion Mobilization Model During Haemodialysis with Time-Dependent Dialysate Bicarbonate Concentrations

Abstract BACKGROUND AND AIMS The hydrogen ion (H+) mobilization model has been previously shown to describe blood bicarbonate (HCO3) kinetics during haemodialysis (HD), but this model has only been evaluated when the dialysate HCO3 concentration ([HCO3]) was constant throughout the treatment [1]. To further assess the H+ mobilization model, we tested its ability to describe blood HCO3 kinetics during HD treatments with a time-dependent dialysate [HCO3]. METHOD The H+ mobilization model describes the time dependence of blood [HCO3] assuming HCO3 is distributed in the extracellular fluid volume and removed from that space by mobilization of H+ from buffers and other sources as previously described [1]. HCO3 transfer across the haemodialyzer during HD is assumed governed primarily by diffusion and the difference between dialysate and blood [HCO3]. In this work, we evaluated this model by comparing its predictions with data from a recent clinical study where blood [HCO3] was measured in 11 chronic, thrice-weekly HD patients (5 male, 6 female) during 4-h treatments with i) constant dialysate [HCO3] of 35 mEq/L; ii) dialysate [HCO3] of 35 mEq/L for the first 2-h and 30 mEq/L for the second 2-h; and iii) dialysate [HCO3] of 30 mEq/L for the first 2-h and 35 mEq/L for the second 2-h. Treatment interventions were fixed during a given week, and arterial blood samples were obtained at the start of treatment and every hour during the first, second and third treatments of the week. Blood acid-base composition was determined using a blood gas analyzer; [HCO3] was calculated from measured pH and partial pressure of carbon dioxide using the Henderson–Hasselbalch equation. The H+ mobilization model was used to determine the H+ mobilization parameter (mH+) by comparing the time dependence of the measured blood [HCO3] with that predicted by the model using nonlinear regression; a total of 66 HD treatments were monitored. Determination of similar mH+ values for each patient, independent of the time-dependent dialysate [HCO3], would demonstrate model validity. RESULTS Example fits of model predictions to blood HCO3 kinetic data from one patient for all three treatment types are shown in the Figure. For all patients, mH+ values during treatments A, B and C were 139 ± 68 (mean ± standard deviation) mL/min, 178 ± 96 mL/min and 156 ± 55 mL/min; they were not statistically different from each other (P = 0.43). The sum of the squared differences between the measured [HCO3] and that predicted by the model (mEq2/L2) was similar during treatments A, B and C (1.48 versus 1.85 versus 1.61), indicating a similar degree of model fit to the data. CONCLUSION This work supports the validity of the H+ mobilization model to describe intradialytic blood HCO3 kinetics with a time-dependent dialysate [HCO3]. Further work is needed to validate the model during post-dialytic and interdialytic periods.

Implantable Loop Recorder Monitoring and the Incidence of Previously Unrecognized Atrial Fibrillation in Patients on Hemodialysis

IntroductionAtrial fibrillation (AF) is common in patients with kidney failure on hemodialysis (KF-HD). We determined both AF incidence and burden in patients with KF-HD using implantable loop recorder (ILR) monitoring.MethodsPatients with KF-HD were enrolled and received an ILR. In 6 monitoring months, the incidence of AF events lasting ≥6 minutes was captured. Demographic, clinical, and dialysis characteristics were collected, and associations with incident AF were estimated using negative binomial regression models and expressed as incidence rate ratios and 95% CIs.ResultsWe enrolled 66 patients with KF-HD (mean age = 56 years, 70% male); 59 (90%) were without previously diagnosed AF. AF lasting ≥6 minutes was detected in 18 of 59 subjects (31%) without previously diagnosed AF and in 5 of 7 subjects (71%) with a previous AF diagnosis. Among the 23 with detected AF, episodes were present on 16% of patient days. Although 14 of 23 patients (61%) had AF on <5% of monitored days, the average duration of AF episodes was <1 hour in 13 of 23 patients (52%). Among patients with AF ≥6 minutes, 19 of 23 (83%) had a CHA2DS2-VASc score ≥2. When investigating individual HD parameters, higher dialysate calcium (>2.5 vs. 2.5 mEq/l: incidence rate ratio = 0.62; 95% CI, 0.48–0.80) was associated with lower AF risk whereas higher dialysate bicarbonate concentrations (>35 vs. 35 mEq/l: incidence rate ratio = 3.18; 95% CI, 1.13–8.94) were associated with higher AF risk.ConclusionNew AF was detected in approximately one-third of patients with KF-HD. AF affects a substantial proportion of patient days and may be an underappreciated cause of stroke in KF-HD.

Modeling acid-base transport in hemodialyzers

One important objective of the hemodialysis treatment is the neutralization of interdialytic acid generation by transport of bicarbonate and other buffer bases from dialysis fluid to the patient via the hemodialyzer. Quantification of solute transport in hemodialyzers, in general, employs the concept of dialysance, a parameter that is often constant for given flow conditions, smaller than both the blood and dialysate flow rates, and independent of the solute concentration difference between blood and dialysate. This approach has been applied to bicarbonate transport in hemodialyzers, but such an approach neglects the transport of dissolved carbon dioxide (CO2) between dialysate and plasma, chemical equilibrium between bicarbonate and CO2, and other acid-base chemical reactions within blood. We describe a novel, one-dimensional model of bicarbonate and CO2 transport in hemodialyzers. The model equations were solved numerically and fitted to published data to estimate mass transfer-area coefficients for the relevant chemical species. Base excess in blood was assumed constant in the hemodialyzer. Simulations were performed for a dialysate bicarbonate concentration of 32 mEq/L at constant blood and dialysate flow rates and different plasma bicarbonate concentrations at the inlet of the hemodialyzer, both with and without CO2 transport. In the latter case, the bicarbonate mass transfer-area coefficient was adjusted to achieve the same total carbon dioxide transport. Calculated dialysance for CO2 exceeded the blood flow rate due to its conversion from bicarbonate in the hemodialyzer, and all calculated dialysances varied with inlet plasma bicarbonate concentration. We concluded that acid-base transport in hemodialyzers cannot be universally characterized by dialysances that are always less than the blood flow rate and independent of the concentration difference between dialysate and blood.

P0005TIME-VARYING DIALYSATE BICARBONATE CONCENTRATIONS CAN REDUCE PEAK INTRADIALTIC SERUM BICARBONATE CONCENTRATIONS

Abstract Background and Aims Hemodialysis (HD) treatments using bicarbonate-containing dialysis solutions can result in large intradialytic increases in serum bicarbonate concentration, potentially inducing intradialytic alkalemia. It has been suggested that a time-varying, compared with a constant, dialysate bicarbonate concentration may limit the intradialytic increase in serum bicarbonate concentration (Tobvin &amp; Sherman, Semin Dial 2016). We tested this hypothesis using a mathematical model of bicarbonate transport during HD. Method We used the H+ mobilization model describing bicarbonate transport during HD (Sargent et al, Semin Dial 2018) to compare intradialytic serum bicarbonate concentrations when using constant or time-varying dialysate bicarbonate concentrations that deliver the same total amount of buffer base to the patient during the HD treatment. We employed this model to evaluate different time-varying dialysate bicarbonate concentration profiles that started at a high value and then decreased as a step function with a 10-minute timing resolution. Dialysis time was 210 minutes, dialysis solutions were assumed to contain acetate at 3 mEq/L, and all kinetic parameters were assumed to be identical to those reported by Sargent et al (Semin Dial 2018). All results with time-varying dialysate bicarbonate concentrations were compared to a constant dialysate concentration of 32 mEq/L. Results Example results comparing time-varying (36.0 mEq/L for the initial 40 min, 31.2 mEq/L thereafter) and constant (32 mEq/L) dialysate bicarbonate concentrations are shown in the figure. The time-varying dialysate bicarbonate concentration lowered the peak intradialytic serum bicarbonate by 0.4 mEq/L for approximately one-half of the treatment. Similar reductions in the peak intradialytic serum bicarbonate concentration could be achieved if the initial high dialysate bicarbonate concentration was 37.6 mEq/L for 30 min or 40.8 for 20 min. The optimal initial high dialysate bicarbonate concentrations and the reduction in the peak intradialytic serum bicarbonate concentrations were somewhat dependent on the assumed patient-dependent H+ mobilization coefficient. Conclusion We conclude that a time-varying dialysate bicarbonate concentration can lower the peak intradialytic serum bicarbonate concentrations while delivering the same total amount of buffer base to the patient. Whether this approach will yield improved patient outcomes requires further evaluation.

P1120QUANTIFICATION OF ACID-BASE TRANSPORT IN HEMODIALYZERS

Abstract Background and Aims Quantification of bicarbonate and dissolved carbon dioxide (CO2) transport in hemodialyzers can be described by the product of a dialysance (D) and their respective concentration differences between dialysate and plasma. It is typically assumed that D values are constant for a given hemodialyzer and flow conditions; however, this approach neglects the chemical interconversion of bicarbonate and dissolved CO2 within blood. We assessed the validity of this approach by developing a comprehensive mathematical model of acid-base transport in hemodialyzers. Method Mass balance relationships in a hemodialyzer were defined using a one-dimensional model with counter-current flows of blood and dialysate. The molecular biochemistry of bicarbonate, dissolved CO2, and non-bicarbonate buffer in both plasma and erythrocytes, together with carbaminohemoglobins within erythrocytes, was assumed to be in equilibrium as described by Rees and Andreassen (Crit Rev Biomed Eng 2005). The model equations were solved numerically, and optimal mass transfer-area coefficients for bicarbonate and dissolved CO2 were determined by comparing model predictions with the data from Sombolos et al (Artif Organs 2005). The latter data included measured concentrations of bicarbonate and dissolved CO2 in plasma and dialysate inlet and outlet flows at a blood flow rate of 300 mL/min, dialysate flow rate of 700 mL/min, and dialysate bicarbonate concentration of 32.5 mEq/L. Base excess of blood was assumed as -5 mEq/L. Model simulations then evaluated the effect of the plasma bicarbonate concentration at the blood inlet (assuming constant mass transfer-area coefficients and flow rates) on D for both bicarbonate (Dbic) and dissolved CO2 (DCO2). D values were calculated as the loss of the molecule from the dialysate divided by the difference in inlet concentrations of dialysate and plasma. Results Optimal mass transfer-area coefficients for bicarbonate and dissolved CO2 were 396 and 1360 mL/min, respectively. Simulation results at different plasma bicarbonate concentrations at the blood inlet ([Bicarbonate]) as expected during a typical hemodialysis treatment are tabulated: Conclusion Quantification of acid-base transport in hemodialyzers requires dialysance values for bicarbonate and dissolved CO2 that are not constant but instead are dependent on the plasma bicarbonate concentration at the blood inlet for a given hemodialyzer at fixed blood and dialysate flow rates.

P1478LOWERING PREVALENCE OF ALKALOSIS AND IMPROVING ADHERENCE TO BICARBONATE TARGETS AMONGST HAEMODIALYSIS PATIENTS THROUGH THE USE OF REDUCED DIALYSATE BICARBONATE

Abstract Background and Aims There is evidence that metabolic alkalosis in haemodialysis patients is harmful. Bommer et al demonstrated association between extremes of bicarbonate and clinical outcomes with significantly increased risk of mortality and hospitalisation with pre-dialysis serum bicarbonate &amp;gt;27mmol/L and &amp;lt;17mmol/L. No overall increased mortality risk was observed with moderate pre-dialysis acidosis (serum bicarbonate 19.1-23.0mmol/L). 2015 Renal Registry Data demonstrated 64.3% of haemodialysis patients overall had bicarbonates within target (18-24mmol/L) compared to 65.7% within our centre. Our reported mean pre-dialysis bicarbonate of 23.7mmol/L was above the mean serum bicarbonate 23.2mmol/L seen nationally. In addition, 33.7% of patients were alkalotic, with bicarbonates &amp;gt;24mmol/L. Given concerns of adverse patient outcomes with extremes of bicarbonate, we aimed to investigate whether reducing our dialysate bicarbonate would culminate in overall attainment of bicarbonate targets. Method Mid-week pre-dialysis bicarbonate levels were measured from in centre haemodialysis patients once monthly, from May to August 2017, across 7 dialysis units within our renal service. Following this, in early 2018, we reduced dialysate bicarbonate concentration from 32mmol/L to 31mmol/L. Monthly midweek pre-dialysis bicarbonate levels were then re-measured in March and April 2019. Results Initial analysis of 2103 pre-dialysis bicarbonate levels across May to August 2017 demonstrated median monthly bicarbonate levels of 24.0–25.0mmol/L. 40.7–54.2% (n=199-322) were alkalotic with pre-dialysis bicarbonates &amp;gt;24mmol/L across this period. Of note, 15-23% (n=66-120) had bicarbonate levels associated with increased mortality and hospitalisation (i.e. &amp;lt;17mmol/L or &amp;gt;27 mmol/L. Subsequent analysis of 1070 bicarbonate levels in March and April 2019 demonstrated a reduction in median pre-dialysis bicarbonate to 22.0mmol/L. Similarly, the proportion of alkalotic patients fell to 11.9–15.3% (n=71-91). 5-9% (n=26-46) bicarbonates were &amp;lt;17 or &amp;gt;27mmol/L. In March 2019, 77.9% of patients had serum bicarbonates in target range compared to 65.7% reported in 2015 overall. Conclusion Initial findings demonstrated substantial alkalosis amongst our dialysis population. A simple measure of altering dialysate by 1mmol/L achieved reductions in overall alkalaemia, and in turn, reduced the percentage of patients with bicarbonate values theoretically correlating with increased mortality and hospitalization risk. We have demonstrated that a small change in dialysate bicarbonate increased concordance with bicarbonate targets, without subsequent increased acidaemia. The extent to which adherence with such targets impacts on patient survival and morbidity remains an ongoing debate.

Optimization of dialysate bicarbonate in patients treated with online haemodiafiltration.

BackgroundMetabolic acidosis is a common problem in haemodialysis patients, but acidosis overcorrection has been associated with higher mortality. There is no clear definition of the optimal serum bicarbonate target or dialysate bicarbonate. This study analysed the impact of reducing dialysate bicarbonate from 35 to 32 mEq/L on plasma bicarbonate levels in a cohort of patients treated with online haemodiafiltration (OL-HDF).MethodsWe performed a prospective cohort study with patients in a stable chronic OL-HDF programme for at least 12 months in the Hospital Clinic of Barcelona. We analysed pre- and post-dialysis total carbon dioxide(TCO2) before and after dialysate bicarbonate reduction from 35 to 32 mEq/L, as well as the number of patients with a pre- and post-dialysis TCO2 within 19–25 and ≤29 mEq/L, respectively, after the bicarbonate modification. Changes in serum sodium, potassium, calcium, phosphorous and parathyroid hormone (PTH) were also assessed.ResultsWe included 84 patients with a 6-month follow-up. At 6 months, pre- and post-dialysis TCO2 significantly decreased (26.78 ± 1.26 at baseline to 23.69 ± 1.92 mEq/L and 31.91 ± 0.91 to 27.58 ± 1.36 mEq/L, respectively). The number of patients with a pre-dialysis TCO2 >25 mEq/L was significantly reduced from 80 (90.5%) to 17 (20.2%) and for post-dialysis TCO2 >29 mEq/L this number was reduced from 83 (98.8%) to 9 (10.7%). PTH significantly decreased from 226.09 (range 172–296) to 182.50 (125–239) pg/mL at 6 months (P < 0.05) and post-dialysis potassium decreased from 3.16 ± 0.30 to 2.95 ± 0.48 mEq/L at 6 months (P < 0.05). Sodium, pre-dialysis potassium, calcium and phosphorous did not change significantly.ConclusionsReducing dialysate bicarbonate concentration by 3 mEq/L significantly and safely decreased pre- and post-dialysis TCO2, avoiding acidosis overcorrection and improving secondary hyperparathyroidism control. An individualized bicarbonate prescription (a key factor in the adequate control of acidosis) according to pre-dialysis TCO2 is suggested based on these results.

Acid-base kinetics during hemodialysis using bicarbonate and lactate as dialysate buffer bases based on the H+ mobilization model.

The H+ mobilization model has been recently reported to accurately describe intradialytic kinetics of plasma bicarbonate concentration; however, the ability of this model to predict changing bicarbonate kinetics after altering the hemodialysis treatment prescription is unclear. We considered the H+ mobilization model as a pseudo-one-compartment model and showed theoretically that it can be used to determine the acid generation (or production) rate for hemodialysis patients at steady state. It was then demonstrated how changes in predialytic, intradialytic, and immediate postdialytic plasma bicarbonate (or total carbon dioxide) concentrations can be calculated after altering the hemodialysis treatment prescription. Example calculations showed that the H+ mobilization model when considered as a pseudo-one-compartment model predicted increases or decreases in plasma total carbon dioxide concentrations throughout the entire treatment when the dialysate bicarbonate concentration is increased or decreased, respectively, during conventional thrice weekly hemodialysis treatments. It was further shown that this model allowed prediction of the change in plasma total carbon dioxide concentration after transfer of patients from conventional thrice weekly to daily hemodialysis using both bicarbonate and lactate as dialysate buffer bases. The H+ mobilization model can predict changes in plasma bicarbonate or total carbon dioxide concentration during hemodialysis after altering the hemodialysis treatment prescription.

Serum Bicarbonate as a Surrogate for pH in Hemodialysis: A Pilot Study

Rationale & ObjectiveExcess morbidity and mortality are associated with both high and low serum bicarbonate levels in epidemiologic studies of patients with end-stage kidney disease (ESKD) receiving hemodialysis. The Kidney Disease Outcomes Quality Initiative (KDOQI) recommends modifying dialysate bicarbonate concentration to achieve a predialysis serum bicarbonate level ≥ 22 mmol/L, measured as total carbon dioxide (CO2). This practice assumes that total CO2 is an adequate surrogate for acid-base status, yet its surrogacy performance is unknown in ESKD. We determined acid-base status at the beginning and end of hemodialysis using total CO2 and pH and tested whether total CO2 is an appropriate surrogate for acid-base status.Study DesignPilot study.Setting & Participants25 veterans with ESKD receiving outpatient hemodialysis.Tests ComparedpH, calculated bicarbonate level, and total CO2.OutcomesThe proportion of paired samples for which total CO2 misclassified acid-base status according to pH was determined. Bias of total CO2 was evaluated using Bland-Altman plots, comparing it to calculated bicarbonate.ResultsAmong 71 samples, mean pH was 7.41 ± 0.03 predialysis and 7.48 ± 0.05 postdialysis. Compared with interpretation of full blood gas profiles, 9 of 25 (36%) participants were misclassified as acidemic using predialysis total CO2 measures alone (total CO2 < 22 mmol/L but pH ≥ 7.38); 1 (4%) participant was misclassified as alkalemic (total CO2 > 26 mmol/L but pH ≤ 7.42). Among paired samples in which predialysis total CO2 was < 22 mmol/L, the corresponding pH was acidemic (< 7.38) in just 3 of 13 (23%) instances.LimitationsSmall, single-center, entirely male cohort.ConclusionsA majority of participants became alkalemic during routine hemodialysis despite arriving with normal pH. 10 of 25 (40%) participants’ acid-base status was misclassified using total CO2 measurements alone; the majority of predialysis total CO2 values that would trigger therapeutic modification according to practice guidelines did not have acidemia when assessed using pH. Efforts to improve dialysis prescription require recognition that total CO2 may not be reliable for interpreting acid-base status in hemodialysis patients.

Effect of Increase in Dialysate Bicarbonate Concentration on Acid-Base and Respiratory Status of Hemodialysis Patients

The appropriate hemodialysis (HD) dialysate bicarbonate (BIC) concentration (DBIC) isn’t clear.

Effect of dialysate potassium and lactate on serum potassium and bicarbonate concentrations during daily hemodialysis at low dialysate flow rates

BackgroundObservational studies of hemodialysis patients treated thrice weekly have shown that serum and dialysate potassium and bicarbonate concentrations are associated with patient outcomes. The effect of more frequent hemodialysis on serum potassium and bicarbonate concentrations has rarely been studied, especially for treatments at low dialysate flow rate.MethodsThese post-hoc analyses evaluated data from patients who transferred from in-center hemodialysis (HD) to daily HD at low dialysate flow rates during the FREEDOM Study. The primary outcomes were the change in predialysis serum potassium and bicarbonate concentrations after transfer from in-center HD (mean during the last 3 months) to daily HD (mean during the first 3 months).ResultsAfter transfer from in-center HD to daily HD (data from 345 patients, 51 ± 15 years of age, mean ± standard deviation), predialysis serum potassium decreased (P < 0.001) by approximately 0.4 mEq/L when dialysate potassium concentration during daily HD was 1 mEq/L; no change occurred when dialysate potassium concentration during daily HD was 2 mEq/L. After transfer from in-center HD to daily HD (data from 284 patients, 51 ± 15 years of age), predialysis serum bicarbonate concentration decreased (P = 0.0022) by 1.0 ± 3.3 mEq/L when dialysate lactate concentration was 40 mEq/L but increased (P < 0.001) by 2.5 ± 3.5 mEq/L when dialysate lactate concentration was 45 mEq/L. These relationships were dependent on serum potassium and bicarbonate concentrations during in-center HD.ConclusionsControl of serum potassium and bicarbonate concentrations during daily HD at low dialysate flow rates is readily achievable; the choice of dialysate potassium and lactate concentration can be informed when transfer is from in-center HD to daily HD.