Postdialysis Rebound Research Articles

MO596: Intradialysis Exercise at the Beginning Versus end of the Dialysis Session: Effect on the Dialysis Dose

Abstract BACKGROUND AND AIMS There is controversy over whether intradialysis exercise has an effect on the dialysis dose. Moreover, theoretical models indicate that intradialytic exercise performed at the end of session may have a beneficial effect in postdialysis rebound. Perhaps this effect of exercise at the end of dialysis can improve the dialysis dose. The aim in this study is to determine the effect of intradialysis exercise on dialysis dose, as well as its effect on dialysis dose when performed during the first two or the last two hours of dialysis session. METHOD This study is a randomized clinical trial. Patients were randomized to exercise in the first (Start group) or last two hours (End group) of dialysis session. Intradialysis exercise consists of a video game adapted to dialysis: Treasure hunting. It is a non-immersive virtual-reality game in which the patient must catch some objectives avoiding obstacles by moving the lower limbs. The exercise session lasts from 20 to 40 min. Intensity was checked through the rate of perceived exertion. Dialysis dose was measured through Kt/V single pool (Kt/V sp), urea reduction percentage (URP), KT and dialisance Kt/V (Kt/Vds) in the short period between dialysis, midweek. These was determined in two different weeks, in one week patients were at rest and in the other week patients did intradialysis exercise. The lean tissue mass (LTM) was determined by multi-frequency stereoscopic bioimpedance. This study is funding from Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 del Gobierno de España. RESULTS This is an open recruitment study, at the time of this communication 29 patients are active, 14 in Start group and 15 in End group. Age mean (SD) 74 (12) years, males 17, Charlson's Index 8.1 (2.24), time on hemodialysys treatment 55.72 (57.67) months, central venous catheter 8, HDFOL 8. A mixed analysis of repeated measures has been developed with each measure of dialysis dose as the dependent variable (Kt/Vsp, URP, KT and Kt/V ds) and independent variables: group (Start versus End), duration of exercise session and LTM. There were no differences in dialysis dose between Start and End groups. Duration of exercise session significantly increased the dialysis dose (Kt/Vsp + 0.015, P = 0.007, URP + 0.23 P = 0.01 and Kt/V ds + 0.015, P = 0.01). CONCLUSION The time of the dialysis session in which physical exercise is performed does not influence the dialysis dose. Longer duration of the intradialysis exercise session increases the dialysis dose.

Efficacy of Supra-HFR in Removing FGF23 and Cytokines: A Single Session Analysis.

Supra hemodiafiltration with reinfusion of the endogenous ultrafiltrate (Supra-HFR) is a dialysis technique used to improve uremic toxin removal in the range of the middle molecular weight molecules. Supra-HFR does not require the preparation and online infusion of high-purity dialysis water because it allows the production of an endogenous ultrafiltrate that undergoes detoxification through an adsorbing resin. We investigated the ability of Supra-HFR to remove fibroblast growth factor 23 (FGF23), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and transforming growth factor alpha (TGF-alpha) after a single session dialysis in nine patients affected by end stage renal disease (ESRD). The same patients underwent a single session of online hemodiafiltration (OL-HDF) to evaluate possible differences in FGF23 and IL-6 levels. A significant reduction in FGF23 was observed with both Supra-HFR (p=0.001) and OL-HDF. As for TNF-alpha and TGF-alpha, which were measured using Supra-HFR only, their percentage values were significantly lower at the end of dialysis than at the start (p=0.0028 and p=0.03, respectively). This did not change with post-dialysis rebound. Supra-HFR was found to have no effect on IL-6 and IL-8. Interestingly, the removal rate for FGF23 and IL-6 was similar to that observed with OL-HDF. Supra-HFR was not superior to OL-HDF, with suboptimal convective volume in the removal of the molecules tested, especially FGF23, which is considered a large middle molecular weight uremic toxin.

Pharmacokinetics and dosing of vancomycin in patients undergoing sustained low efficiency daily diafiltration (SLEDD-f): A prospective study

The pharmacokinetics of vancomycin in patients who undergo sustained low efficiency daily diafiltration (SLEDD-f) is not clear. This study aimed to determine the appropriate vancomycin dosage regimen for patients receiving SLEDD-f. This prospectively observational study enrolled critically ill patients older than 18 years old that used SLEDD-f as renal replacement therapy and received vancomycin treatment. An 8-h SLEDD-f was performed with FX-60 (high-flux helixone membrane, 1.4m2). Serial blood samples were collected before, during, and after SLEDD-f to analyse vancomycin serum concentrations. Effluent fluid samples (a mixture of dialysate and ultrafiltrate) were also collected to determine the amount of vancomycin removal. Seventeen patients were enrolled, and 10 completed the study. The amount of vancomycin removal was 447.4±88.8mg (about 78.4±18.4% of the dose administered before SLEDD-f). The vancomycin concentration was reduced by 57.5±14.9% during SLEDD-f, and this reduction was followed by a rebound with duration of one to three hours. The elimination half-life of vancomycin decreased from 64.1±35.7h before SLEDD-f to 7.0±3.0h during SLEDD-f. Significant amount of vancomycin removed during SLEDD-f. Despite the existence of post-dialysis rebound, a sufficient supplemental dose is necessary to maintain therapeutic range.

P0959EFFECT ON THE DIALYSIS DOSE OF THE EXERCISE WITH VIRTUAL REALITY DURING THE FIRST VERSUS SECOND PART OF THE DIALYSIS SESSION

Abstract Background and Aims Exercise using non-immersive virtual reality (VR) is a novel rehabilitation method for patients undergoing hemodialysis treatment. This method has shown in a pilot study improved physical function and health-related quality of life. There is controversy about the effect of intradialysis exercise on the dialysis dose. Furthermore, theoretical models also indicate that intradialytic exercise at the end of session may be beneficial in postdialysis rebound. Objective: to determine effect of exercise with virtual reality during the first two hours and the last two hours of dialysis session on postdialysis rebound and dialysis dose. Method The design was a randomized clinical trial. Patients were randomized to exercise in the first (Start group) or last two hours (End group) of dialysis session. Dialysis dose was measured through the monocompartimental Kt/V, and the potassium, urea, phosphorus and creatinine rebound was calculated after both baseline and exercise sessions at 17 weeks. Intradialysis exercise consisted of a video game adapted to dialysis: Treasure hunting. It is a non-immersive VR game in which the patient must catch some objectives avoiding obstacles by moving the lower limbs. The exercise session lasted from 20 to 40 minutes. Intensity was checked through the rate of perceived exertion. An mixed ANOVA of repeated measures was used to assess the effect of the intervention. Patients exercised for 17 weeks. Results 43 patients participated, 11 dropouts, 17 in Start group and 15 in End group. Mean age 73 years, males 28. There were no significant differences in rebound urea, creatinine, potassium and phosphorus 30 minutes after finishing dialysis. The mean baseline Kt/V was 1.65 (SD 0.21) and with exercise 1.75 (SD 0.25). The mixed ANOVA analysis showed a significant time effect with an increase in Kt/V (mean 0.10, 95% CI 0.02-0.19, p 0.018) from exercise session vs baseline. No group per time significant interaction was found, so that there was no difference in the dialysis dose between Start and End group. Conclusion Intra-dialysis exercise with virtual reality can improve the dose of dialysis, no matter the timing of the exercise is performed.

P1113TREATMENT OF ACUTE LITHIUM INTOXICATION WITH SUSTAINED LOW-EFFICIENCY DIALYSIS (SLED)

Abstract Background and Aims Lithium salts are widely used in psychiatry for prophylaxis and treatment of bipolar affective disorders. Given its narrow therapeutic range, drug overdosage is not infrequent, and lithium intoxication has potentially fatal neurologic and cardiac side effects. Owing to its low molecular weight (7 Da), relatively small volume of distribution, and its negligible protein binding, lithium can be efficiently removed by any extracorporeal modality of renal replacement therapy (RRT). Although conventional intermittent haemodialysis (IHD) is effective in promptly cleating lithium, postdialysis rebound is common. The use of sustained low-efficiency dialysis (SLED) in lithium intoxication seems to be a valid therapeutic strategy, but strong evidence is still lacking in the literature. We present here two cases of lithium intoxication, in one case acute (naïve patient) and in the other case acute-on-chronic (a deliberate overdose in a patient previously on lithium therapy), successfully treated with SLED. Method: Patient A - A 47 years-old woman without history of lithium consumption was admitted to the ER. after a voluntary acute lithium ingestion of 40 tablets of lithium carbonate (8.12 mEq lithium each). Notwithstanding treatment with intravenous crystalloids and gastric lavage, lithium concentration increased up to 4.18 mEq/l at about 24 h after admission. She developed mental status changes, oliguria, hypotension and bradycardia. Patient B – A 58 years-old man on lithium therapy for bipolar syndrome was admitted to ER after a voluntary acute lithium ingestion of an unknown quantity of lithium carbonate tablets. Lithium concentration, after an initial level of 0.4 mEq/L, increased up to 4.35 mEq/l about 15 h from admission, despite irst-line therapies with intravenous crystalloids and gastric lavage were promptly started. His mental status worsened, together with oliguria, bradycardia and hypotension. Results: Patient A - A 8-hour SLED session with regional citrate anticoagulation (RCA) was planned [blood flow rate (Qb) 200 mL/min; dialysis fluid rate (Qd) 300 mL/min; countercurrent flow direction]. Lithium serum levels decreased by 87% during treatment (0.55 mEq/L), and the patient fully awoke recovering a normal mental status within the first 4 h of treatment. SLED was completed safely within the prescribed time. After the end of treatment, lithium rebound was unremarkable and renal function completely recovered and the patients was discharged after 3 days. Patient B - A 12-hour SLED session with RCA was planned (Qb 200 mL/min; Qd 500 mL/min; countercurrent flow direction). Serum lithium levels decreased by 55% (2.10 mEq/L) during treatment, and the patient awoke, recovering a normal mental status. At the end of treatment, rebound of lithium concentration was observed at 4 hours from SLED end detected (from 2.1 to 2.5 mEq/L), with initial signs of mental deterioration. A second SLED (12 h) was performed, with the same operative parameters and, by the end of the second treatment, lithium concentration was 0.49 mEq/L. Afterward, mental status and renal function fully recovered and no rebound rebound was observed. The patient was discharged after 6 days. Conclusion SLED could represent a good therapeutic strategy to treat acute lithium intoxication, providing an initial rapid clearance with resolution of symptoms, and limiting major rebound.

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.

Update on Postdialysis Rebound by a New Technology in Hemodialysis.

After dialysis ends, urea continued movement causes rebound postdialysis, with values at about 20%. New techniques have been incorporated into hemodialysis, but their relationship with rebound has not yet been studied. This study aimed to quantify urea rebound at 30-min postdialysis during sessions using polysulfone filters and high-flow versus online hemodiafiltration, and to define its correlation with body composition measured by bioimpedance by a cross-sectional study with 69 patients (December 2015 to January 2016). Mean urea rebound was 24.39, which was positively associated with recirculation, Kt/V or hypotension, and showed a negative relationship with online hemodiafiltration. It was not associated with different body composition compartments. To conclude, postdialysis urea rebound remained high with polysulfone dialyzers and low dialysis doses. Online hemodiafiltration could improve postdialysis urea rebound. Different body composition compartments were not related to rebound.

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.

Distribution volume assessment compartment modelling: theoretic phosphate kinetics in steady state hemodialys patients.

Hyperphosphatemia constitutes a major problem in end-stage renal disease patients. At this stage, dialysis efficacy usually plays an important role in obtaining phosphate levels within the normal range. Currently, no practical tool capable of making individualized predictions about phosphate changes during and after hemodialysis (HD) have gained clinical acceptance. As a result, optimal dialysis prescriptions seem to be difficult to achieve. The objective of the present study was to develop and test a quantitative tool to predict intradialytic and postdialytic (2 hours) phosphate kinetics in HD therapy. This included distribution volume assessment. The approach included compartment modeling. Various model attempts were produced and tested using experimental data that included 2 treatment regimens; conventional and nocturnal HD, with 2-hour postdialysis rebound. Graphical comparison and determination of R(2) was applied to determine the best model variation. 1-, 2- and 3-compartment simulations were produced. Both 2- and 3-compartment model variations showed a close fit with the experimental data. However, a 3-compartment model showed the best graphical fit. This was supported by R(2) values in the 0.951-0.979 range. The 3-compartment model seems promising for prediction about plasma phosphate and holds the potential to be employed as a decision support tool and to enhance optimal dialysis prescriptions. Furthermore, the results provide specific suggestions about the distribution of phosphate in the body. Despite the promising results, further data and testing are necessary to validate the initial results.

Urea Rebound Assessment Based on UV Absorbance in Spent Dialysate.

The aim of the study was to examine the possibility of postdialysis urea rebound assessment using UV-absorbance measurements in spent dialysate. Twenty-six patients on chronic three-times-a-week hemodialysis (HD) were studied in two separate studies. Double-beam spectrophotometer was used for the determination of UV absorbance in the collected spent dialysate samples. Also, on-line UV absorbance was monitored. The equilibrium concentration (C(eq)) of urea at the end of the rebound phase was calculated based on urea concentration in blood and dialysate and UV absorbance in spent dialysate. Based on C(eq), urea rebound was expressed relative to urea concentration at the end of HD (R1) and relative to the decrease in urea concentration during HD (R2). Estimates based on UV-absorbance values in spent dialysate (R(1_a), R(2_a)) slightly over assess postdialysis rebound compared with results based on the blood sample drawn 30 min after HD (R(1_30post), R(2_30post)), but R(1_a) and R(2_a) presented greater consistency and accuracy compared with the estimates based on the intradialytic blood sample (R(1_b), R(2_b)). In summary, the results show that it is possible to assess postdialysis urea rebound in blood based on UV-absorbance measurements in spent dialysate.

Determinants of phosphorus mobilization during hemodialysis

Our recent work proposed a pseudo one-compartment model for describing intradialysis and postdialysis rebound kinetics of phosphorus. In this model, phosphorus is removed directly from a central distribution volume with the rate of phosphorus mobilization from a second, very large compartment proportional to the phosphorus mobilization clearance. Here, we evaluated factors of phosphorus mobilization clearance and postdialysis central distribution volume from 774 patients in the HEMO Study. Phosphorus mobilization clearance and postdialysis central distribution volume were 87 (65, 116) ml/min, median (interquartile range), and 9.4 (7.2, 12.0) liter, respectively. The phosphorus mobilization clearance was significantly higher for male patients than for female patients. Both the phosphorus mobilization clearance and the postdialysis central distribution volume were significantly associated with postdialysis body weight but negatively with the predialysis serum phosphorus concentration. The postdialysis central distribution volume was also significantly associated with age. Overall, the postdialysis central distribution volume was 13.6% of the postdialysis body weight. Thus, the phosphorus mobilization clearance during hemodialysis is higher when predialysis serum phosphorus concentration is low and higher in male patients than in female patients. The central distribution volume of phosphorus is a space approximating the extracellular fluid volume.

Patient-specific phosphorus mobilization clearance during nocturnal and short daily hemodialysis

The kinetics of plasma phosphorus during different hemodialysis (HD) modalities are incompletely understood. We recently demonstrated that a pseudo one-compartment kinetic model including phosphorus mobilization from various body compartments into extracellular fluids can describe intradialytic and postdialytic rebound kinetics of plasma phosphorus during conventional and short 2-hour HD treatments. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter, the phosphorus mobilization clearance (K(M)). In this report we determined K(M) in patients treated by in-center nocturnal HD (ICNHD) and short daily HD (SDHD) with low dialyzer phosphate clearance. In the ICNHD study, eight patients underwent 8-hour HD treatments where intradialytic and postdialytic plasma samples were collected; K(M) values were determined by nonlinear regression of plasma concentration as a function of time. In the SDHD study, five patients were studied during 28 treatments for approximately 3 hours. Here, K(M) was calculated using only predialytic and postdialytic plasma phosphorus concentrations. Dialyzer phosphate clearances were 134 ± 20 (mean ± SD) and 95 ± 16 mL/min during ICNHD and SDHD, respectively. K(M) values for the respective therapies were 124 ± 83 and 103 ± 33 mL/min, comparable to those determined previously during conventional and short HD treatments of 98 ± 44 mL/min. When results from ICNHD, SDHD, and previous HD modalities were combined, K(M) was directly correlated with postdialytic body weight (r = 0.38, P = 0.025) and inversely correlated with predialytic phosphorus concentration (r = -0.47, P = 0.005). These findings suggest that phosphorus kinetics during various HD modalities can be described by a pseudo one-compartment model.

A simple method to estimate phosphorus mobilization in hemodialysis using only predialytic and postdialytic blood samples

We have recently developed a pseudo one-compartment model to describe intradialytic and postdialytic rebound kinetics of plasma phosphorus. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter; the phosphorus mobilization clearance (K(M) ). In this work, we propose a simple method to estimate K(M) from predialytic and postdialytic plasma phosphorus concentrations. Clinical data were collected from 22 chronic hemodialysis patients that underwent a 4-hour treatment session. A simple algebraic equation was derived from the pseudo one-compartment model to determine K(M) from predialytic and postdialytic plasma phosphorus concentrations. K(M) values computed using this equation were compared with values obtained from nonlinear regression of the full kinetic model to frequent intradialytic and postdialytic measurements of plasma phosphorus concentrations. There was good agreement between K(M) values (concordance correlation coefficient of 0.94) obtained from the simple method (105 ± 52 mL/min, mean ± SD) and from the full model (99 ± 47 mL/min). The 95% confidence interval for the difference between estimated K(M) values was -26 to 36 mL/min. The proposed simple method requires the use of only predialytic and postdialytic blood samples to estimate patient specific K(M) ; this approach may allow easy clinical evaluation of phosphorus kinetics in hemodialysis patients.

A Regional Blood Flow Model for β2-Microglobulin Kinetics and for Simulating Intra-dialytic Exercise Effect

A kinetic model based on first principles, for β(2)-microglobulin, is presented to obtain precise parameter estimates for individual patient. To reduce the model complexity, the number of model parameters was reduced using a priori identifiability analysis. The model validity was confirmed with the clinical data of ten renal patients on post-dilution hemodiafiltration. The model fit resulted in toxin distribution volume (V(d)) of 14.22 ± 0.75 L, plasma fraction in extracellular compartment (f(P)) of 0.39 ± 0.03, and inter-compartmental clearance of 44 ± 4.1 mL min(-1). Parameter estimates suggest that V(d) and f(P) are much higher in hemodialysis patients than in normal subjects. The developed model predicts larger removed toxin mass than that predicted by the two-pool model. On the application front, the developed model was employed to explain the effect of intra-dialytic exercise on toxin removal. The presented simulations suggest that intra-dialytic exercise not only increases the blood flow to low flow region, but also decreases the inter-compartmental resistance. Combined, they lead to increased toxin removal during dialysis and reduced post-dialysis rebound. The developed model can assist in suggesting the improved dialysis dose based on β(2)-microglobulin, and also lead to quantitative inclusion of intra-dialytic exercise in the future.

Leptin and β2-Microglobulin Kinetics with Three Different Dialysis Modalities

Leptin is a protein produced by fat cells and involved in body weight regulation. In patients with normal kidney function, leptin has been considered an independent predictor of cardiovascular events. In uremic patients, leptin in plasma serum was assumed to be associated with malnutrition, inflammation and atherosclerosis. Because of its molecular weight and characteristics, leptin can be considered as a protein-bound uremic retention solute. Some authors have reported the possibility of decreasing the serum leptin concentration with high flux membranes, but limited data are available on the elimination with medium-flux membranes or alternative dialysis strategies such as hemodiafiltration. We evaluated the kinetics of leptin and beta2m in a study of 18 chronic hemodialysis patients using low-flux, medium-flux and high-flux biocompatible membranes, the last one used in hemodiafiltration (HDF). Blood samples for leptin and beta2m were collected pre- and post-treatment and 30 minutes after the end of treatment, over a 1-week period that included 3 dialysis sessions. Clearances of leptin and beta2m across the dialyzer were also determined directly from the arterial and venous blood concentrations 60 and 210 minutes after starting dialysis. At baseline, all groups showed similar leptin (18.8+/-4.4 ng/mL) and beta2m concentrations (29.2+/-7.1 ng/mL). After a single dialysis session, a reduction of both solutes was observed with HDF (39.8+/-1.9%, 78.1+/-4.9) and medium flux membranes (18.2+/-0.9%, 52.2+/-1.7%), whereas the concentrations remained unchanged with the low-flux membranes. After one-week period, a trend of reduction of plasma pre dialysis leptin and beta2m were observed with HDF and medium flux membranes. At 60 minutes, HDF showed the best instantaneous clearance across the filter for leptin (56.2+/-10.1 ml/min) and beta2m (75.3+/-4.4 ml/min). The magnitude of post dialysis rebound of leptin at 30 min was variable and strongly correlated with the instantaneous clearance of the solute (r2= 0.88). Leptin serum concentration can be influenced by dialysis modalities and membrane permeability; data on rebound suggest a multicompartimental kinetic of leptin similar to beta2m. Leptin removal, as measured by the reduction rate, can be considered as an index of dialysis efficiency for protein-bound uremic retention solutes.

Effects of Efficiency and Length of Acetate-Free Biofiltration Session on Postdialysis Solute Rebound

Postdialytic rebound (PDR) of plasma solutes is a relevant drawback of intermittent hemodialysis, but its pathophysiological process remains undefined. We assessed the independent effects of efficiency and length of dialytic session on PDR of urea, phosphate, and potassium. Uremic patients were evaluated at the beginning and end of dialysis and after 180 minutes in 2 randomized crossover studies. In study 1, we compared the effect of standard versus higher efficiency acetate-free biofiltration (AFB) while maintaining the same duration of 4 hours. In study 2, we compared the effect of 3- versus 5-hour AFB sessions while maintaining similar efficiency. In study 1, greater Kt/V (1.49 +/- 0.20 versus 1.22 +/- 0.15; P < 0.0001) was coupled with significant increases in both absolute removal and PDR of urea and phosphate (PDR of urea, +45% versus +29%; PDR of phosphate, +79% versus +52%), but not of potassium. Similarly, in study 2, shortening the AFB session while maintaining similar absolute removal and Kt/V (1.28 +/- 0.09 versus 1.31 +/- 0.09) significantly increased PDR of urea and phosphate (PDR of urea, +32% versus +19%; PDR of phosphate, +63% versus +36%), but not of potassium. In both studies, greater PDRs of urea and phosphate were associated with estimated greater removal of these solutes per hour. The rate of removal of phosphate and urea is a critical determinant of their PDR; conversely, potassium is not influenced by removal rate, likely because of its marked cell compartmentalization.

Kinetics of β2‐Microglobulin and Phosphate during Hemodialysis: Effects of Treatment Frequency and Duration

Current understanding of beta2-microglobulin (beta2M) and phosphate (or inorganic phosphorus) kinetics during hemodialysis is reviewed. The postdialysis:predialysis concentration ratio for beta2M is determined by dialyzer clearance for beta2M, treatment time, patient body size (specifically, extracellular fluid volume), and total ultrafiltration volume during the treatment. Evaluation of these treatment parameters can be used to calculate dialyzer clearance for beta2M; however, such calculated values are only approximations, since they neglect intradialytic generation, nonrenal (nondialyzer) clearance, and postdialysis rebound of beta2M. The detailed kinetics of beta2M during hemodialysis are best described using a two-compartment model. Theoretical predictions from such two-compartment models suggest that the product of dialyzer clearance for beta2M and weekly treatment duration, independent of treatment frequency, is the main determinant of plasma beta2M concentrations. The kinetics of phosphate removal during hemodialysis are incompletely understood. Phosphate is removed from both extracellular and intracellular compartments during hemodialysis; the plasma phosphate concentration levels off after the first 1 or 2 hours of treatment and plasma concentrations can rebound even before therapy is complete. Increases in dialyzer clearance of phosphate have been previously achieved only by increasing dialysis membrane surface area or by the use of hemodiafiltration. A four-compartment model of phosphate kinetics proposed recently by Spalding et al. suggests that the major barrier to phosphate removal is limited transfer of phosphate between the intracellular and extracellular compartments, although other complex factors also play important roles. Theoretical predictions using the model of Spalding et al. suggest that increasing either treatment frequency or treatment duration can increase phosphate removal. The kinetics of beta2M are representative of middle molecules whose removal during hemodialysis is governed predominantly by clearance at the dialyzer. In contrast, phosphate removal is limited primarily by its sequestration in the intracellular compartment (and possibly other compartments), not by its clearance at the dialyzer. The kinetics of phosphate may therefore be representative of uremic toxins whose removal is limited by sequestration into compartments or by protein binding. Enhanced removal of both of these uremic toxins using a given therapy will require treatments of increased frequency and longer duration.

Kinetics, dialysis systems, adequacy Postdialysis rebound in a case of acute methanol poisoning

Introduction: Methanol poisoning can lead to complications that include metabolic acidosis, visual impairment and death. Treatment options include ethanol, fomepizole, and hemodialysis (HD). Objective: To report on the occurrence of post dialysis methanol rebound during treatment. Method and Findings: A 40‐year‐old male with a history of schizophrenia and suicide attempts presented to the emergency room after reportedly ingesting 1 quart of windshield washer fluid. The patient presented with a preliminary blood chemistry of methanol 390 mg/dL, ethanol 48 mg/dL, glucose 93 mg/dL, Na 138 meq/L, K 3.8 meq/L, Cl 98 mmol/L, CO2 26 mmol/L, urea 16 mg/dL, creatinine 1.2 mg/dL, and an anion gap of 14 mmol/L. The patient was started on 1360 mg of fomepizole (12:50 AM) followed by HD for 4 hours. A second dose of fomepizole (900 mg) was administered at 8:00 AM. In addition, another HD session was started at 12:00 PM and continued for 4 hours. A third dose of fomepizole (700 mg) was administered at 8:50 PM. Finally, a third HD session was started the next day at 3:05 PM and lasted 3 hours. Table 1 illustrates methanol levels in relation to each HD session. Findings: Methanol concentration after the first HD increased from 100 mg/dL to 127 mg/dL (27%) in 5 h 20 m. It also increased from 35 mg/dL to 50 mg/dL (43%) 14 h 45 m after the second HD. Conclusions: Close attention must be paid to the potential for post dialysis methanol rebound. It is recommended that methanol levels continue to be monitored for several hours after HD. Methanol levels before and after each hemodialysis Start HD #1 (2:40 AM) End HD #1 (6:40 AM) Start HD#2 (12:00 PM) End HD#2 (4:00 PM) Next Day (6:45 AM) Methanol (mg/dL) 324 100 127 35 50 Rebound 27% 43%

Kinetics of urea and β2-microglobulin during and after short hemodialysis treatments

Daily short hemodialysis (HD) is often prescribed by simply doubling treatment frequency and halving treatment time; however, the effect of this prescription approach on the equilibrated HD dose (urea eKt/V) and whole body clearance for beta(2)-microglobulin has not been established. We compared urea and beta(2)-microglobulin kinetics during and 60 minutes after a short HD treatment and a conventional HD treatment in a crossover study on 22 maintenance HD patients: 16 male and 6 female, 61 +/- 18 (mean +/- standard deviation) years of age. One patient in each treatment modality was excluded from certain analyses because of missing data. Short and conventional HD treatments were essentially identical, except for treatment times, which were 116 +/- 14 and 241 +/- 27 minutes, respectively. Blood samples were collected at regular intervals during and after treatments, and additional blood and dialysate samples were collected at 60 minutes of treatment to evaluate dialyzer clearances. Plasma water urea clearances measured directly across the dialyzer during short and conventional HD treatments were not different (255 +/- 23 mL/min and 255 +/- 28 mL/min, respectively). The 60-minute postdialysis blood urea nitrogen concentration rebounded more (P < 0.01) after short HD than conventional HD (5.9 +/- 3.1 vs. 4.0 +/- 1.5 mg/dL, respectively). Calculated urea eKt/V values using the Daugirdas-Schneditz rate equation were not different from those measured during conventional HD using the 60-minute postdialysis concentration but significantly overestimated measured urea eKt/V values during short HD. Postdialysis rebound of beta(2)-microglobulin concentrations was variable but similar after short and conventional HD treatments (0.1 +/- 3.4 vs. 0.7 +/- 1.8 mg/L, respectively). Whole body clearances of beta(2)-microglobulin calculated from predialysis and immediate (10-second) postdialysis serum concentrations during short and conventional HD treatments were not different from each other (42.9 +/- 24.1 vs. 41.9 +/- 22.4 mL/min, respectively). These observations show that the Daugirdas-Schneditz rate equation is accurate in predicting urea eKt/V during conventional, but not during short, HD. In contrast, whole body clearances of beta(2)-microglobulin during short and conventional HD treatments were similar. We conclude that calculation of accurate estimates of urea eKt/V, but not clearances of beta(2)-microglobulin, differ during short and conventional HD treatments.

持続的血液ろ過透析が有用であった重症慢性リチウム中毒の１症例

Hemodialysis is the usual recommended treatment for severe lithium intoxication when emergent extracorporeal lithium removal is necessary. Intermittent hemodialysis has been chosen most frequently, however it has disadvantages such as postdialysis rebound elevation in lithium concentration, hemodynamic instability, tendency to develop hypovolemia and deteriolate renal function. On the other hand continuous hemodiafiltration (CHDF) offers an advantage of slow sustained removal of lithium without the adverse effects of conventional hemodialysis. The following is a report of a case of severe chronic lithium intoxication successfully treated with CHDF. A 69-year old woman, who had been diagnosed with manic-depressive psychosis 18 years previously, was transferred to our ICU because of unconsciousness during lithium maintenance therapy (lithium carbonate 800mg/day). On arrival her consciousness level was Japan Coma Scale 100 and the pulse rate was 30beats/min. Since she had a past history of cardiac failure, we conducted CHDF to accelerate lithium elimination. CHDF was continued for 64 hours and thereafter her condition improved uneventfully.