Evaluating hydrogen ion mobilization during hemodialysis using only predialysis and postdialysis blood bicarbonate concentrations.

INTRODUCTION: The hydrogen ion (H+) mobilization model has been previously shown to provide a quantitative description of intradialytic changes in blood bicarbonate (HCO3) concentration during hemodialysis (HD). The current study evaluated the accuracy of different methods for estimating the H+ mobilization parameter (Hm) from this model. METHODS: The study compared estimates of the H+ mobilization parameter using predialysis, hourly during the HD treatment, and postdialysis blood HCO3 concentrations (Hm-full2) with those determined using only predialysis and postdialysis blood HCO3 concentrations assuming steady state conditions (Hm-SS2) during the midweek treatment in 24 chronic HD patients treated thrice weekly. RESULTS: Estimated Hm-full2 values (0.163 ± 0.079 L/min [mean ± standard deviation]) were higher than, but not statistically different (p = 0.067) from, those of Hm-SS2 (0.152 ± 0.065 L/min); the values of Hm-full2 and Hm-SS2 were highly correlated with a correlation coefficient of 0.948 and a mean difference that was small (0.011 L/min). Further, the H+ mobilization parameter values calculated using only predialysis and postdialysis blood HCO3 concentrations during the first and third HD treatments of the week were not different from those calculated during the midweek treatment. CONCLUSIONS: The H+ mobilization model can be used to provide estimates of the H+ mobilization parameter without the need to measure hourly intradialytic blood HCO3 concentrations.

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.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

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

BACKGROUND: 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]. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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].

Mathematical modelling of bicarbonate supplementation and acid-base chemistry in kidney failure patients on hemodialysis.

Acid-base regulation by the kidneys is largely missing in end-stage renal disease patients undergoing hemodialysis (HD). Bicarbonate is added to the dialysis fluid during HD to replenish the buffers in the body and neutralize interdialytic acid accumulation. Predicting HD outcomes with mathematical models can help select the optimal patient-specific dialysate composition, but the kinetics of bicarbonate are difficult to quantify, because of the many factors involved in the regulation of the bicarbonate buffer in bodily fluids. We implemented a mathematical model of dissolved CO2 and bicarbonate transport that describes the changes in acid-base equilibrium induced by HD to assess the kinetics of bicarbonate, dissolved CO2, and other buffers not only in plasma but also in erythrocytes, interstitial fluid, and tissue cells; the model also includes respiratory control over the partial pressures of CO2 and oxygen. Clinical data were used to fit the model and identify missing parameters used in theoretical simulations. Our results demonstrate the feasibility of the model in describing the changes to acid-base homeostasis typical of HD, and highlight the importance of respiratory regulation during HD.

Modeling acid-base balance during continuous kidney replacement therapy.

Clinical studies have suggested that use of bicarbonate-containing substitution and dialysis fluids during continuous kidney replacement therapy may result in excessive increases in the carbon dioxide concentration of blood; however, the technical parameters governing such changes are unclear. The current work used a mathematical model of acid-base chemistry of blood to predict its composition within and exiting the extracorporeal circuit during continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodiafiltration (CVVHDF). Model predictions showed that a total substitution fluid infusion rate of 2 L/h (33% predilution) with a bicarbonate concentration of 32 mEq/L during CVVH at a blood flow rate of 200 mL/min resulted in only modest increases in plasma bicarbonate concentration by 2.0 mEq/L and partial pressure of dissolved carbon dioxide by 4.4 mmHg in blood exiting the extracorporeal circuit. The relative increase in bicarbonate concentration (9.7%) was similar to that in partial pressure of dissolved carbon dioxide (8.2%), resulting in no significant change in plasma pH in the blood exiting the CVVH circuit. The changes in plasma acid-base levels were larger with a higher infusion rate of substitution fluid but smaller with a higher blood flow rate or use of substitution fluid with a lower bicarbonate concentration (22 mEq/L). Under comparable flow conditions and substitution fluid composition, model predicted changes in acid-base levels during CVVHDF were similar, but smaller, than those during CVVH. The described mathematical model can predict the effect of operating conditions on acid-base balance within and exiting the extracorporeal circuit during continuous kidney replacement therapy.

Targeting arterial partial pressure of carbon dioxide in acute respiratory distress syndrome patients using extracorporeal carbon dioxide removal.

BACKGROUND: A retrospective analysis of SUPERNOVA trial data showed that reductions in tidal volume to ultraprotective levels without significant increases in arterial partial pressure of carbon dioxide (PaCO2 ) for critically ill, mechanically ventilated patients with acute respiratory distress syndrome (ARDS) depends on the rate of extracorporeal carbon dioxide removal (ECCO2 R). METHODS: We used a whole-body mathematical model of acid-base balance to quantify the effect of altering carbon dioxide (CO2 ) removal rates using different ECCO2 R devices to achieve target PaCO2 levels in ARDS patients. Specifically, we predicted the effect of using a new, larger surface area PrismaLung+ device instead of the original PrismaLung device on the results from two multicenter clinical studies in critically ill, mechanically ventilated ARDS patients. RESULTS: After calibrating model parameters to the clinical study data using the PrismaLung device, model predictions determined optimal extracorporeal blood flow rates for the PrismaLung+ and mechanical ventilation frequencies to obtain target PaCO2 levels of 45 and 50 mm Hg in mild and moderate ARDS patients treated at a tidal volume of 3.98 ml/kg predicted body weight (PW). Comparable model predictions showed that reductions in tidal volumes below 6 ml/kg PBW may be difficult for acidotic highly severe ARDS patients with acute kidney injury and high CO2 production rates using a PrismaLung+ device in-series with a continuous venovenous hemofiltration device. CONCLUSIONS: The described model provides guidance on achieving target PaCO2 levels in mechanically ventilated ARDS patients using protective and ultraprotective tidal volumes when increasing CO2 removal rates from ECCO2 R devices.

Modeling acid-base balance for in-series extracorporeal carbon dioxide removal and continuous venovenous hemofiltration devices.

Patients with acute respiratory distress syndrome and acute kidney injury (AKI) treated by kidney replacement therapy may also require treatment with extracorporeal carbon dioxide removal (ECCO2 R) devices to permit protective or ultraprotective mechanical ventilation. We developed a mathematical model of acid-base balance during extracorporeal therapy using ECCO2 R and continuous venovenous hemofiltration (CVVH) devices applied in series for the treatment of mechanically ventilated AKI patients. Published data from clinical studies of mechanically ventilated AKI patients treated by CVVH at known infusion rates of substitution fluid without ECCO2 R were used to adjust the model parameters to fit plasma levels of arterial partial pressure of carbon dioxide (PaCO2 ), arterial plasma bicarbonate concentration ([HCO3 ]), and plasma pH (as well as certain other unmeasured physiological variables). The effects of applying ECCO2 R at an unchanged and a reduced tidal volume on PaCO2 , [HCO3 ] and plasma pH were then simulated assuming carbon dioxide removal rates from the ECCO2 R device measured in the clinical studies. Agreement of such model predictions with clinical data was good whether the ECCO2 R device was positioned proximal or distal to the CVVH device in the extracorporeal circuit. Although carbon dioxide removal rates from the ECCO2 R device measured in one previous clinical study were higher when it was placed proximal to the CVVH device, suggesting that such in-series positioning was optimal, the current mathematical model demonstrates that proximal positioning of the ECCO2 R device also results in lower bicarbonate (and, therefore, total carbon dioxide) removal from the distal CVVH device. Thus, the removal of total carbon dioxide by such extracorporeal circuits is relatively independent of the position of the in-series devices. It is concluded that the described mathematical model has quantitative accuracy; these results suggest that the overall acid-base balance when using ECCO2 R and CVVH devices in a single extracorporeal circuit will be similar, independent of their in-series position.

Optimizing serum total carbon dioxide concentration during short and nocturnal frequent hemodialysis using lactate as dialysate buffer base.

INTRODUCTION: Definitive clinical studies to determine the optimal dialysate lactate concentration to prescribe during frequent hemodialysis when using the NxStage System One dialysis delivery system at low dialysate flow rates have not been reported. METHODS: We used clinical data from patients who transferred from in-center thrice-weekly hemodialysis (ICHD) to daily home hemodialysis using the NxStage System One and the H+ mobilization model to calculate acid generation rates in patient sub-groups during the FREEDOM study. Assuming those acid generation rates were representative, we then predicted using the H+ mobilization model the effect of using dialysate lactate concentrations of 40 and 45 mEq/L on predialysis serum total carbon dioxide (tCO2 ) concentrations in patients who transfer from ICHD to short and nocturnal frequent hemodialysis prescriptions used in current clinical practice; the prescriptions evaluated varied by treatment frequency, dialysate volume per treatment, and treatment times. FINDINGS: With frequencies of four to six treatments per week and treatment times of 170 to 210 minutes per treatment, the effect of dialysate lactate concentration was primarily dependent on weekly dialysate volume. For weekly dialysate volumes of 150 to 160 L per week, use of dialysate lactate concentrations of 45 mEq/L, but not 40 mEq/L, resulted in an increase of predialysis serum tCO2 concentration. When longer treatment times typical of nocturnal frequent hemodialysis were evaluated, model predictions showed that the use of dialysate lactate concentration of 45 mEq/L may not be appropriate for many patients because of excessive increases in predialysis serum tCO2 concentration. Reducing dialysate volume from 60 to 30 L may limit the increase in predialysis serum tCO2 concentration when patients transfer from ICHD to nocturnal frequent hemodialysis. DISCUSSION: Predictions from the H+ mobilization model show that dialysate lactate concentration and weekly dialysate volume are the primary prescription parameters for optimizing predialysis serum tCO2 concentration during short and nocturnal frequent hemodialysis.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The H+ mobilization model can predict changes in plasma bicarbonate or total carbon dioxide concentration during hemodialysis after altering the hemodialysis treatment prescription.

Extracorporeal carbon dioxide removal requirements for ultraprotective mechanical ventilation: Mathematical model predictions.

Extracorporeal carbon dioxide (CO2 ) removal (ECCO2 R) facilitates the use of low tidal volumes during protective or ultraprotective mechanical ventilation when managing patients with acute respiratory distress syndrome (ARDS); however, the rate of ECCO2 R required to avoid hypercapnia remains unclear. We calculated ECCO2 R rate requirements to maintain arterial partial pressure of CO2 (PaCO2 ) at clinically desirable levels in mechanically ventilated ARDS patients using a six-compartment mathematical model of CO2 and oxygen (O2 ) biochemistry and whole-body transport with the inclusion of an ECCO2 R device for extracorporeal veno-venous removal of CO2 . The model assumes steady state conditions. Model compartments were lung capillary blood, arterial blood, venous blood, post-ECCO2 R venous blood, interstitial fluid and tissue cells, with CO2 and O2 distribution within each compartment; biochemistry included equilibrium among bicarbonate and non-bicarbonate buffers and CO2 and O2 binding to hemoglobin to elucidate Bohr and Haldane effects. O2 consumption and CO2 production rates were assumed proportional to predicted body weight (PBW) and adjusted to achieve reported arterial partial pressure of O2 and a PaCO2 level of 46 mmHg at a tidal volume of 7.6 mL/kg PBW in the absence of an ECCO2 R device based on average data from LUNG SAFE. Model calculations showed that ECCO2 R rates required to achieve mild permissive hypercapnia (PaCO2 of 46 mmHg) at a ventilation frequency or respiratory rate of 20.8/min during mechanical ventilation increased when tidal volumes decreased from 7.6 to 3 mL/kg PBW. Higher ECCO2R rates were required to achieve normocapnia (PaCO2 of 40 mmHg). Model calculations also showed that required ECCO2R rates were lower when ventilation frequencies were increased from 20.8/min to 26/min. The current mathematical model predicts that ECCO2R rates resulting in clinically desirable PaCO2 levels at tidal volumes of 5-6 mL/kg PBW can likely be achieved in mechanically ventilated ARDS patients with current technologies; use of ultraprotective tidal volumes (3-4 mL/kg PBW) may be challenging unless high mechanical ventilation frequencies are used.

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

BACKGROUND: Observational 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. METHODS: These 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). RESULTS: After 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. CONCLUSIONS: Control 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.

Differential Molecular Modeling Predictions of Mid and Conventional Dialysate Flows.

BACKGROUND: High dialysate flow rates (QD) of 500-800 mL/min are used to maximize urea removal during conventional hemodialysis. There are few data describing hemodialysis with use of mid-rate QD (300 mL/min). METHODS: We constructed uremic solute (urea, beta2-microglobulin and phosphate) kinetic models at varying volumes of distribution and blood flow rates to predict solute clearances at QD of 300 and 500 mL/min. RESULTS: Across a range of volumes of distribution a QD of 300 mL/min generally yields a predicted urea spKt/V greater than 1.2 during typical treatment times with a small difference in urea spKt/V between a QD of 300 and 500 mL/min. A larger urea KoA dialyzer and 15 min of additional time narrows the urea spKt/V difference. No substantial differences were observed regarding the kinetics of beta2-microglobulin and phosphate for QD of 300 vs. 500 mL/min. CONCLUSION: A QD of 300 mL/min can achieve urea clearance targets. Hemodialysis systems using mid-rate QD can be expected to provide adequate hemodialysis, as currently defined.

Volume of urea cleared as a therapy dosing guide for more frequent hemodialysis.

INTRODUCTION: With dialysis delivery systems that operate at low dialysate flow rates, prescriptions for more frequent hemodialysis (HD) employ dialysate volume as the primary parameter for small solute removal rather than blood-side urea dialyzer clearance (K). Such delivery systems, however, yield dialysate concentrations that almost completely saturate with blood (water), suggesting that the volume of urea cleared (the product of K and treatment time or Kt) can be readily estimated from the prescribed dialysate volume to target small solute removal. Methods For more frequent HD, we examined the volume of urea cleared per treatment required to achieve a minimal dose of small solute removal, comparing results based on body surface area (BSA) with those based on KDOQI clinical practice guidelines, that is, a weekly stdKt/V of 2.1. Estimates of the target volume of urea cleared were calculated for 4, 5, and 6 treatments per week, and compared for patients with different anthropometric estimates of total body water volume (Vant ). BSA was assumed proportional to Vant0.8 , and residual kidney function was neglected. Findings Whether based on BSA or weekly stdKt/V of 2.1, the target volume of urea cleared per treatment required to achieve a minimal dose of small solute removal was lower at higher treatment frequency. As with conventional thrice-weekly HD, target volumes of urea cleared for more frequent HD based on BSA were larger for patients with small Vant and smaller for patients with large Vant than those based on a weekly stdKt/V of 2.1. Discussion Prescription of more frequent HD using the volume of urea cleared per treatment, calculated from the prescribed dialysate volume, is simple in principle and can be readily implemented in clinical practice when using dialysis delivery systems that operate at low dialysate flow rates. Other aspects of dialysis adequacy require additional consideration.

Intradialytic kinetics of middle molecules during hemodialysis and hemodiafiltration.

BACKGROUND: The kinetics of ß2-microglobulin during hemodialysis and hemodiafiltration is well described by a two-compartment model where clearance by the dialyzer is from a central compartment volume that approximates plasma volume and a total distribution volume that approximates extracellular fluid volume. The kinetics of middle molecules with molecular weights larger than ß2-microglobulin have not been extensively studied. METHODS: Intradialytic plasma concentrations and overall dialyzer clearances of ß2-microglobulin (11.8 kD), myoglobin (16.7 kD) and complement factor D (24.4 kD) were used to estimate three kinetic parameters from a two-compartment model, namely intercompartmental clearance, central compartment volume and total distribution volume, in hemodialysis patients; these data were collected during two clinical trials of medium cut-off dialyzers (with extended middle molecule removal) during hemodialysis and high-flux dialyzers during hemodialysis and hemodiafiltration. In the current exploratory analyses, the kinetic parameters from all dialyzers were combined. Overall dialyzer clearance was evaluated by total mass removed in the dialysate. RESULTS: In total, 345 sets of kinetic parameters from 35 patients were determined. Intercompartmental clearance and central compartment volume for myoglobin and complement factor D were smaller (P < 0.001) than those for ß2-microglobulin. Independent of middle molecule, intercompartmental clearance and central compartment volume were associated with overall dialyzer clearance (P < 0.001), but total distribution volume was not (P = 0.083). CONCLUSIONS: A two-compartment kinetic model can only describe intradialytic kinetics of middle molecules with molecular weights larger than ß2-microglobulin if the central compartment is small and dependent on overall dialyzer clearance.

Calculating Standard Kt/V during Hemodialysis Based on Urea Mass Removed.

BACKGROUND/AIMS: We derived a novel equation for calculating weekly urea standard Kt/V (stdKt/V) during hemodialysis (HD) based on urea mass removed, comparable to the approach during peritoneal dialysis. METHODS: Theoretical consideration of urea mass balance during HD led to the following equation for stdKt/V, namely, stdKt/V = N × (URR + UFV/V), where N is the number of treatments per week, URR is urea reduction ratio per treatment, UFV is ultrafiltration volume per treatment, and V is postdialysis urea distribution volume. URR required corrections for postdialysis rebound and intradialytic urea generation. We compared the accuracy of this approach with previous equations for stdKt/V by numerical simulations using a 2-compartment model of urea kinetics for thrice-weekly and more frequent HD prescriptions. RESULTS: The proposed equation based on urea mass removed predicted values of stdKt/V that are equivalent to those calculated by previous equations for stdKt/V. CONCLUSION: This work provides a novel approach for calculating stdKt/V during HD and strengthens the theoretical understanding of stdKt/V.

Removal of vancomycin administered during dialysis by a high-flux dialyzer.

INTRODUCTION: Hemodialysis patients frequently receive vancomycin for treatment of gram-positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high-flux polyamide dialyzers. METHODS: This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high-flux (Polyflux 24R) dialyzer (Phase 2). There was a three-week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. FINDINGS: Dialysis removed 35 ± 15% (range 18-56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0-44.5 hours from the start of infusion were similar between the two phases (AUCPhase 1 884 ± 124 mg-hr/L, mean ± SD; AUCPhase 2 856 ± 208 mg-hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). DISCUSSION: When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high-flux HD membrane with a 24R Polyflux dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra-dialysis dosing is empirically increased to account for intra-dialytic drug removal.

A Pseudo-One Compartment Model of Phosphorus Kinetics During Hemodialysis: Further Supporting Evidence.

A pseudo-one compartment model has been proposed to describe phosphorus kinetics during hemodialysis and the immediate post-dialysis period. This model assumes that phosphorus mobilization from tissues is proportional to the difference between the pre-dialysis serum concentration (a constant) and the instantaneous serum concentration. The current study is exploratory and evaluated the ability of a pseudo-one compartment model to describe the kinetics of phosphorus during two short hemodialysis treatments separated by a 60-min inter-treatment period without dialysis; the latter is the post-dialysis rebound period for the first short hemodialysis treatment. Serum was collected frequently during both hemodialysis treatments and the inter-treatment period to assess phosphorus kinetics in 21 chronic hemodialysis patients. Phosphorus mobilization clearance and pre-dialysis central distribution volume were previously estimated for each patient during the first hemodialysis treatment and the inter-treatment period. Assuming those kinetic parameters remained constant for each patient, serum phosphorus concentrations during the second treatment were used to estimate the driving force concentration (Cdf ) for phosphorus mobilization from tissues during the second treatment. Treatment time (117 ± 14 [mean ± standard deviation] vs. 117 ± 14 min), dialyzer phosphorus clearance (151 ± 25 vs. 140 ± 32 mL/min), and net fluid removal (1.44 ± 0.74 vs. 1.47 ± 0.76 L) were similar during both short hemodialysis treatments. Measured phosphorus concentration at the start of the second hemodialysis treatment (3.3 ± 0.9 mg/dL) was lower (P < 0.001) than at the start of the first treatment or Cpre (5.4 ± 1.9 mg/dL). Calculated Cdf was 4.9 ± 2.0 mg/dL, not significantly different from Cpre (P = 0.12). Cdf and Cpre were correlated (R = 0.72, P < 0.001). The results from this study demonstrate that the driving force concentration for phosphorus mobilization during hemodialysis is constant and not different from that pre-dialysis, providing further evidence supporting a fundamental assumption of the pseudo-one compartment model.