Bicarbonate Dialysis Research Articles

Association of Dialysate Bicarbonate with Arrhythmia in the Monitoring in Dialysis Study.

Sudden death accounts for ∼25% of deaths among maintenance hemodialysis (HD) patients, occurring more frequently on HD days. Higher dialysate bicarbonate (DBIC) may predispose to alkalemia and arrhythmogenesis. We conducted a 12-month analysis of session-level data from 66 patients with implantable loop recorders. We fit logistic regression and negative binomial mixed effects regression models to assess the association of DBIC with clinically significant arrhythmia (CSA - ventricular tachycardia ≥115 beats per minute (BPM) for at least 30 seconds, bradycardia ≤40 BPM for at least 6 seconds, or asystole for at least 3 seconds) and reviewer confirmed arrhythmia (RCA - implantable-loop-recorder-identified or patient-marked event for which a manual review of the stored ECG tracing confirmed the presence of atrial fibrillation, supraventricular tachycardia, sinus tachycardia with rate >130 BPM, ventricular tachycardia, asystole, or bradycardia). Models adjusted for age, sex, race, HD vintage, vascular access, and pre-HD serum bicarbonate and additionally for serum and dialysate potassium levels. Mean age was 56 ± 12 years, 70% were male, 53% were Black, and 35% were Asian. Fewer RCA episodes were associated with DBIC >35 than 35 mEq/L (incidence rate ratio [IRR] 0.45 (0.27, 0.75) and aIRR 0.54 (0.30, 0.97)), but the association was not significant when adjusting for serum and dialysate potassium levels (aIRR 0.60 (0.32, 1.11)). Otherwise, no associations between DBIC and arrhythmia were identified. We observed a lower frequency of RCA with higher DBIC, compared with DBIC of 35 mEql/L, contrary to our original hypothesis, but this association was attenuated in fully adjusted models. Validation of these findings in larger studies is required, with a further need for interventional studies to explore the optimal DBIC concentration.

Acetate-containing bicarbonate dialysate increases all-cause mortality more than acetate-free bicarbonate dialysate containing citrate in hemodialysis patients

BackgroundNo studies have compared mortality between acetate-containing bicarbonate dialysate (ABD) and acetate-free bicarbonate dialysate containing citrate (AFD) in hemodialysis (HD) or online hemodiafiltration (OHDF). We therefore compared mortality between ABD and AFD in each modality.MethodsThis retrospective observational study included 738 patients who were receiving super high-flux (SHF) or SHF albumin-leaking HD (n = 310: ABD 235 and AFD 75) or OHDF (n = 428: ABD 321 and AFD 107) at our institution between 1 April and 1 July 2017. Three-year all-cause mortality was compared between ABD and AFD in the HD or OHDF groups using a propensity score matching model. Kaplan–Meier survival curves were compared using the log-rank test, and then Cox regression analysis with adjustments was performed for some covariates that remained significant.ResultsAfter propensity score matching, mortality on ABD was not significantly different from that on AFD in the HD group [n = 75; hazard ratio (HR) 2.271, 95% confidence interval (CI) 0.863–5.981, P = 0.087] or in the OHDF group (n = 107; HR 1.944, 95% CI 0.585–6.458, P = 0.269) without adjustments. However, with adjustments using some covariates, mortality was significantly higher on ABD than on AFD (adjusted HR 4.501, 95% CI 1.434–14.125, P = 0.010) in the HD group, but not in the OHDF group.ConclusionsThese findings suggest that ABD worsens mortality more than AFD in patients on SHF and SHF albumin-leaking HD.Trial registration: UMIN Clinical Trials Registry, UMIN000053090. Prospectively registered 13 December 2023, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000060581.

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.

#1235 Comparative effect on bone remodeling and inflammation biomarkers of citrate dialysate and bicarbonate dialysate in HDF-OL patients

Abstract Background and Aims Hemodialysis (HD) treatment increases the inflammatory state of chronic kidney disease (CKD), which is associated with dysregulation of mineral bone metabolism. Reduced inflammation and increased bone formation have been described in Hemodiafiltration (HDF) compared with conventional HD. On the other hand, HD and OL-HDF using citrate-enriched dialysate are known to be safe and anti-inflammatory. However, the effects of post-dilution OL-HDF with citrate dialysate compared to bicarbonate dialysate on biomarkers of bone formation and resorption have not been studied. We aimed to compare the effect of bone remodeling markers and inflammation of different dialysates (citrate vs bicarbonate) in post dilution OL- HDF treatment. Method A total of 33 patients on conventional HD with bicarbonate citrate were included. At month 1, 18 patients, who did not require individualized adjustment of the dialysate composition such as potassium, were changed to HD with citrate dialysate and 15 patients remained with bicarbonate dialysate. By the second month, however, all patients were on OL-HDF with no change in buffer dialysate. Pre-dialysis blood samples were taken in both treatment groups at baseline (prior to the initiation of citrate dialysate in 18 patients), and at the first, second and fifth months after the introduction of citrate. Measurements of mineral homeostasis (calcium, phosphate, magnesium, parathyroid hormone, intact parathyroid hormone), inflammation (interleukin-6, β2-microglobulin, C-reactive protein) and bone remodeling markers (carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX), as a biomarker of bone resorption and procollagen type 1 N-terminal pro-peptide (P1NP), as a biomarker of bone formation) were performed. All samples were collected before a mid-week dialysis session. Mineral homeostasis measurements were also performed before and after HD at the first and second month of the switch to citrate dialysate. Normally distributed data were presented as mean (standard deviation, SD) and median (interquartile range). Intra-subjects comparisons were analyzed using paired sample t-test or Wilcoxon signed-rank test. Comparisons between groups were analyzed using Mann-Whitney U test. Statistical analyses were performed using the SPSS (version 15.0, Chicago, IL, USA). p-value < 0.05. Results Overall, 75.7% (n = 25) of the subjects were male, the median age was 69 years (SD: 12) and 39.3% suffered diabetes (n = 13). Patients on citrate and bicarbonate dialysates were comparable for age, sex, comorbidities, months on dialysis and anemia control. Baseline mineral, bone remodeling and inflammation markers before HD, were also comparable in both groups. Only patients on bicarbonate dialysate had higher β2-microglobulin levels at baseline. Changes in serum levels of mineral, bone remodeling and inflammatory biomarkers at 5 months compared to baseline for both groups are shown in Table 1. After 5 months of follow-up, a 22% trend-reduction (p = 0.08) in P1NP as bone formation biomarker was observed in patients on citrate dialysate compared to those on bicarbonate dialysate. In addition, the fold change observed in CTX as parameter of bone resorption was attenuated in the citrate dialysate group (11% vs 116% in the bicarbonate dialysate group, p < 0.001). β2-microglobulin levels decreased significantly in both groups at 5 months but It is explained by the known effect of OL-HDF treatment on the inflammatory state of dialysis patients. Conclusion In patients on OL-HDF treatment the use of the citrate as dialysate may provide a benefit in bone remodeling by reducing bone resorption and trend to balance the bone formation/resorption. However, our results are in line with previous studies, where caution should be adopted in patients with very high parathyroid hormone levels, as this may be enhanced by reduced mineral turnover.

#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.

The Association of Dialysate Bicarbonate with Cardiac Arrhythmia in the Monitoring in Dialysis (MiD) Study

The Association of Dialysate Bicarbonate with Cardiac Arrhythmia in the Monitoring in Dialysis (MiD) Study

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.

#3827 BICARBONATE PROFILING IN HEMODIALYSIS: MATHEMATICAL MODELING OF DATA FROM A CLINICAL TRIAL

Abstract Background and Aims During hemodialysis (HD), bicarbonate and other bases are added to the dialysis fluid to correct chronic acidosis that may develop in kidney-impaired patients, increasing plasma bicarbonate concentration to physiological levels. Previous studies have shown that both exceedingly high and low post-dialysis bicarbonate concentrations are associated with adverse clinical outcomes; however, no clear guidelines for the prescription of bicarbonate concentration in the dialysis fluid are available. Data from a recent controlled clinical trial, carried out at the Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw (Poland), were used to identify transport parameters of a mathematical model of acid-base homeostasis in HD patients, as the first step in the implementation of a tool to optimize bicarbonate profiling during HD. Method The study was carried out in 20 chronic patients, undergoing thrice weekly 4-hr HD. The patients underwent three treatment regimens: A) constant dialysis fluid bicarbonate concentration (HCO3,D) equal to 35 mEq/L; B) HCO3,D decreasing from 35 to 30 mEq/L after 2 hrs; C) HCO3,D increasing from 30 to 35 mEq/L after 2 hrs. The patients were divided in two cohorts: for the first (n = 11) treatment schedule was: treatment A during the first and third week, B during the second week and C during the fourth week. For the second cohort (n = 9) treatment C was carried out during the second week and treatment B during the fourth. Data were collected only during the second and third sessions of the week, and acid-base composition was determined using a blood gas analyzer. The mathematical model describes the transport of bicarbonate and dissolved CO2 from dialysis fluid to the patient and can predict changes in the acid-base equilibrium of arterial and venous plasma and erythrocytes, interstitial fluid, and tissue cells, using mass transport equations. The dialysances for bicarbonate (KHCO3) and dissolved CO2 (KCO2) were estimated via least square minimization. Results No significant difference was found comparing patients in the two cohorts, or comparing sessions of the same week. Pre-dialysis plasma bicarbonate, pH, or CO2 partial pressure (PCO2) were significantly lower for treatment B compared to treatment A. Average plasma bicarbonate concentrations for the different treatments are shown in Figure 1 for data and model simulations. Table 1 reports the average values of the estimated parameters for week. No statistically significant difference was found between sessions, cohorts, or treatments. The model fitted bicarbonate data with an average error of 2.5 ± 1.4%, and PCO2 with an error of 4.5 ± 3.6%. Simulations of mixed-venous blood, interstitial fluid, and tissue cells concentrations showed a similar response to different treatments as in arterial blood. Conclusion The model accurately describes plasma bicarbonate data with high accuracy regardless of the treatment conditions. The parameters estimated showed considerable variability between treatments (less so between the sessions of the same week), but without statistical significance. The model can be used to simulate the effect of dialysate bicarbonate profiling on acid-base equilibrium in HD patients.

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.

Evaluation of Bacteriology of Bicarbonate Dialysis Solution (BDS) From Hemodialysis (HD) Clinics That Have Adopted Ferric Pyrophosphate Citrate (FPC; Triferic)

Evaluation of Bacteriology of Bicarbonate Dialysis Solution (BDS) From Hemodialysis (HD) Clinics That Have Adopted Ferric Pyrophosphate Citrate (FPC; Triferic)

Citric acid-based bicarbonate dialysate attenuates aortic arch calcification in maintenance hemodialysis patients: a retrospective observational study.

Progression of aortic calcification is associated with all-cause and cardiovascular mortality in hemodialysis patients. Blood calciprotein particle (CPP) levels are associated with coronary artery calcification and were reported to be inhibited when using citric acid-based bicarbonate dialysate (CD). Therefore, this study aimed to examine the effect of CD on the progression of the aortic arch calcification score (AoACS) and blood CPP levels in hemodialysis patients. A 12-month retrospective observational study of 262 hemodialysis patients was conducted. AoACS was evaluated by calculating the number of calcifications in 16 segments of the aortic arch on chest X-ray (minimum score is 0; maximum score is 16 points). The patients were divided into the following groups according to their baseline AoACS: grade 0, AoACS = 0 points; grade 1, AoACS 1-4 points; grade 2, AoACS 5-8 points; grade 3, AoACS 9 points or higher. Patients on bisphosphonates or warfarin or with AoACS grade 3 were excluded. Progression, defined as ΔAoACS (12-month score - baseline score) > 0 points, was compared between the CD and acetic acid-based bicarbonate dialysate (AD) groups before and after adjusting the background using propensity score matching. The AoACS progression rate was significantly lower in the CD group than in the AD group (before matching: P = 0.020, after matching: P = 0.002). Multivariate logistic regression analysis showed that CD was significantly associated with AoACS progression (odds ratio 0.52, 95% confidence interval 0.29‒0.92, P = 0.025). CD may slow the progression of vascular calcification in hemodialysis patients.

Effect of dialysate bicarbonate and sodium on blood pH in maintenance hemodialysis-A prospective study.

The validity of adjusting dialysate bicarbonate based on pre-hemodialysis (HD) serum bicarbonate is unclear. There are no studies of the impact of dialysate sodium on blood pH. To understand the impact of dialysate bicarbonate and sodium on blood pH. Two hundred arterialized blood samples were obtained on the third session of HD with four configurations of dialysate: sodium (140, 137 mEq/L) and bicarbonate (38, 32 mEq/L). The correlation between pre-HD serum bicarbonate and pH was modest (r=0.6). A lower dialysate sodium (p=0.035) and a higher bicarbonate (p=0.02) associated with a higher post-HD blood pH. The frequency of pre-HD blood pH of <7.4 and a post-HD blood pH of >7.5 did not differ for samples with serum bicarbonate <22, 22-26, or >26 mEq/L. Adjusting dialysate buffer based on pre-HD serum bicarbonate is unnecessary. A higher bicarbonate and lower dialysate sodium associate with post-HD alkalemia.

Hypoxia during maintenance hemodialysis-the critical role of pH.

The impact and management of subclinical hypoxia during hemodialysis is a significant medical challenge. As key determinants of O2 availability and delivery, proposed mechanisms contributing to hypoxia include ischemia, alkalemia and pulmonary leukocyte sequestration. However, no study has comprehensively investigated and compared these interrelated mechanisms throughout a typical hemodialysis treatment week. This study aimed to comprehensively assess the physiological mechanisms that contribute to hypoxia during hemodialysis. In 76 patients, we measured arterial blood gases and pH at four time-points during hemodialysis (start, 15min, 60min, end) over the course of a standard treatment week. For the mid-week hemodialysis session, we additionally measured central hemodynamics (non-invasive cardiac output monitoring) and white blood cell count. Linear regression modelling identified changes in pH, but not central hemodynamics or white blood cell count, to be predictive of changes in PaO2 throughout hemodialysis (e.g. at 60min, β standardized coefficient pH=0.45, model R2=0.25, P<.001). Alkalemia, hypokalemia, decreased calcium and increased hemoglobin-O2 affinity (leftward shift in the oxyhemoglobin dissociation curve) were evident at the end of hemodialysis. pH and hemoglobin-O2 affinity at the start of hemodialysis increased incrementally over the course of a standard treatment week. These data highlight the important role of pH in regulating O2 availability and delivery during hemodialysis. Findings support routine pH monitoring and personalized dialysate bicarbonate prescription to mitigate the significant risk of alkalemia and subclinical hypoxia.

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.

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.

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.

Acetate-Free Biofiltration Versus Online Acetate-Free Hemodiafiltration in Patients at High Risk of Hemodialysis Intolerance

Intradialytic hypotension (IDH) is one of the most frequent1,2 and worrying issues in chronic hemodialysis.3,4 Systolic blood pressure (BP) <90 mm Hg has the strongest association with mortality in patients receiving chronic kidney replacement therapy (CKRT).3 IDH results from the combination of excessive ultrafiltration rate, membrane bio-incompatibility, and inappropriate hemodynamic response (heart rate and contractility, vascular tone).5 Modulation of the dialysate composition can improve tolerance, but standard bicarbonate dialysis remains associated with frequent IDH in patients at high risk.