Total Solute Removal Research Articles

The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins.

The accumulation of protein-bound uremic toxins (PBUT) is associated with increased cardiovascular outcomes in patients on dialysis. However, the efficacy of PBUT removal for a medium-cutoff (MCO) membrane has not been clarified. This study was designed to assess the efficacy of PBUT clearance according to dialysis modalities. In this prospective and cross-over study, we enrolled 22 patients who received maintenance hemodiafiltration (HDF) thrice weekly from three dialysis centers. The dialysis removal of uremic toxins, including urea, beta 2-microglobulin (B2MG), lambda free light chain (λ-FLC), indoxyl sulfate (IS), and p-cresyl sulfate (pCS), was measured in the 22 patients on high-flux HD (HF-HD), post-dilution online HDF (post-OL-HDF), and MCO-HD over 3 weeks. The average convection volume in post-OL-HDF was 21.4 ± 1.8 L per session. The reduction rate (RR) of B2MG was higher in post-OL-HDF than in MCO-HD and HF-HD. The RR of λ-FLC was the highest in MCO-HD, followed by post-OL-HDF and HF-HD. The dialysate albumin was highest in MCO-HD, followed by post-OL-HDF and HF-HD. Post-dialysis plasma levels of IS and pCS were not statistically different across dialysis modalities. The total solute removal and dialytic clearance of IS and pCS were not significantly different. The clearance of IS and pCS did not differ between the HF-HD, post-OL-HDF, and MCO-HD groups.

Improved Dialysis Removal of Protein-Bound Uraemic Toxins with a Combined Displacement and Adsorption Technique

Introduction: Protein-bound uraemic toxins (PBUTs) are poorly removed by conventional dialytic techniques, given their high plasma protein binding, and thus low, free (dialysable) plasma concentration. Here, we evaluated and compared PBUTs removal among conventional haemodialysis (HD), adsorption-based HD, displacement-based HD, and their 2 combinations both in vitro and in vivo. Methods: The removal of PBUTs, including 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresyl sulphate (PCS), indoxyl sulphate (IS), indole-3-acetic acid (3-IAA), and hippuric acid, was first evaluated in an in vitro single-pass HD model. Adsorption consisted of adding 40 g/L bovine serum albumin (Alb) to the dialysate and displacement involved infusing fatty acid (FA) mixtures predialyser. Then, uraemic rats were treated with either conventional HD, Alb-based HD, lipid emulsion infusion-based HD or their combination to calculate the reduction ratio (RR), and the total solute removal (TSR) of solutes after 4 h of therapy. Results: In vitro dialysis revealed that FAs infusion prefilter increased the removal of PCS, IS, and 3-IAA 3.23-fold, 3.01-fold, and 2.24-fold, respectively, compared with baseline and increased the fractional removal of CMPF from undetectable at baseline to 14.33 ± 0.24%, with a dialysis efficacy markedly superior to Alb dialysis. In vivo dialysis showed that ω-6 soybean oil-based lipid emulsion administration resulted in higher RRs and more TSRs for PCS, IS, and 3-IAA after 4-h HD than the control, and the corresponding TSR values for PCS and IS were also significantly increased compared to that of Alb dialysis. Finally, the highest dialysis efficacy for highly bound solute removal was always observed with their combination both in vitro and in vivo. Conclusions: The concept of combined displacement- and adsorption-based dialysis may open up new avenues and possibilities in the field of dialysis to further enhance PBUTs removal in end-stage renal disease.

MO703URINE VOLUME AS A MARKER OF RESIDUAL KIDNEY FUNCTION IN PERITONEAL DIALYSIS PATIENTS: QUANTITATIVE ASSESSMENT

Abstract Background and Aims In dialysis patients, urine volume is an easy-to-obtain marker of residual kidney function but information is lacking of its potential value as an estimate of the renal contribution to total clearance of small solutes. We explored whether correlations of urine volume with different estimations of the residual renal function for urea, creatinine, and phosphorus, could be used to assess renal solute clearances and renal mass removal for investigated solutes. Method In an observational study of 94 non-anuric (urine output ≥ 100 mL per 24 hours) patients (54% men, median age 59 [45 - 68] year, BMI 25.8 [21.4 - 27.7] kg/m2) undergoing automated (n = 59) or continuous ambulatory (n = 35) peritoneal dialysis (PD), we evaluated renal, peritoneal and total (renal plus peritoneal) solute removal (g/week) and clearance (L/week) in relation to urine volume (L/day). Urine volume, renal clearances, ratio of urine solute to serum solute concentration, removed mass of each solute and the ratio of mass removed by urine (renal clearance) over total mass removed by urine and dialysate (total clearance) for urea, creatinine and phosphorus were estimated from 24 h collections of urine and dialysate and determination of solute concentrations in serum, urine and dialysate. Statistical dependence between variables was tested using Spearman’s correlation coefficient (rho). Data are expressed as median with interquartile range. Results Median 24-hour urine output was 560 [323 – 938] mL. Renal mass removal for urea, creatinine and phosphorus was 10.1 [4.5 – 17.1], 3.5 [1.8 – 5.6] and 1.0 [0.4 – 1.7] g/week, respectively. The average contribution of residual renal removal to the total mass removed was 28% [17% - 41%] for urea, 56% [30% - 72%] for creatinine and 44% [24% - 58%] for phosphorus. Serum creatinine correlated weakly and negatively with urine volume (rho = -0.26, p < 0.05), but no such relationship was observed for urea and phosphorus. Only urine concentration of creatinine correlated weakly with urine volume with rho = -0.28 and p < 0.01. Urine concentration over plasma concentration did not correlate with urine volume for any solute. Renal urea clearance (20.1 [11.4 - 35.7] L/week) correlated positively with creatinine renal clearance (43.0 [18.9 - 75.1] L/week), (rho = 0.92), and with phosphorus renal clearance (17.3 [7.6 - 32.9] L/week), (rho = 0.89, p < 0.001; Fig. 1A), while renal creatinine clearance correlated positively with phosphorus renal clearance (rho = 0.86, p<0.001). Urine volume correlated positively with urea, creatinine and phosphorus clearances at rho 0.78, 0.63 and 0.73, respectively (all p< 0.001), and with renal removal of mass of urea, creatinine, and phosphorus with rho= 0.83, 0.68 and 0.74 (Fig. 1B), respectively; all p<0.001. Conclusion In PD patients, solute renal clearances and renal mass removal for urea, creatinine and phosphorus may be predicted from urine volume. Among renal clearances for urea, creatinine, and phosphorus two of them may be assessed based on measurements of the third one.

Improved dialytic removal of protein-bound uremic toxins by intravenous lipid emulsion in chronic kidney disease rats.

Protein-bound uremic toxins (PBUTs) have received extensive attention, as their accumulation leads to pleiotropic toxic biological effects, while the removal of these solutes by conventional dialysis therapies is severely hampered. This study aimed to examine whether increased removal of PBUTs could be achieved with intravenous lipid emulsion (ILE). PBUTs such as 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were spiked with human serum albumin (HSA) solution and the inhibitory effects of free fatty acid (FFA) on the binding of CMPF, PCS and IS to HSA were examined separately in vitro by ultrafiltration. In vitro dialysis of albumin solution was then performed to investigate the effects of fatty acid (FAs) mixtures infusion on the fractional removal of PBUTs. Finally, the inhibitory effect of FFA on the binding of PBUTs to albumin was examined in uremic rats, and blood purification therapy was conducted to calculate the reduction ratio (RR) and the total solute removal (TSR) of solutes. The percentage protein binding of CMPF, PCS and IS decreased significantly with increasing FFAs concentrations, and the inhibitory effect was more remarkable with the addition of oleic acid or linoleic acid than that of eicosapentaenoic acid and docosahexaenoic acid. In vitro infusion of FAs increased the fractional removal of CMPF to 14.40 ± 2.38%. PCS, IS and indole-3-acetic acid removal increased from 8.00 ± 2.43%, 11.68 ± 1.54% and 15.38 ± 3.97%, respectively, at baseline to 28.21 ± 5.99%, 35.42 ± 5.27% and 40.18 ± 5.05%, respectively, when FAs were present. In vivo, rat serum concentrations of free PBUTs were significantly higher in the ILE group than in the control group, and administration of ILE resulted in higher RRs and more TSR for PBUTs after 3 h of hemodialysis (HD) therapy compared with the control group. Administration of ILE effectively increased the dialytic removal of PBUTs. This method could be applied to current HD therapy.

Increasing the removal of protein-bound uremic toxins by liposome-supported hemodialysis.

Protein-bound uremic toxins (PBUTs) accumulate at high plasma levels and cause various deleterious effects in end-stage renal disease patients because their removal by conventional hemodialysis is severely limited by their low free-fraction levels in plasma. Here, we assessed the extent to which solute removal can be increased by adding liposomes to the dialysate. The uptake of liposomes by direct incubation in vitro showed an obvious dose-response relationship for p-cresyl sulfate (PCS) and indoxyl sulfate (IS) but not for hippuric acid (HA). The percent removal of both PCS and IS but not of HA was gradually increased with the increased concentration of liposomes in a rapid equilibrium dialysis setup. In vitro closed circulation showed that adding liposomes to the dialysate markedly increased the dialysances of PBUTs without greatly altering that of urea and creatinine. In vivo experiments in uremic rats demonstrated that adding liposomes to the dialysate resulted in higher reduction ratios (RRs) and more total solute removal (TSR) for several PBUTs compared to the conventional dialysate, which was approximately similar to the addition of bovine serum albumin to the dialysate. These findings highlight that as an adjunct to conventional hemodialysis, addition of liposomes to the dialysate could significantly improve the removal of protein-bound uremic solutes without greatly altering the removal of small, water-soluble solutes.

Protein-bound uraemic toxins, dicarbonyl stress and advanced glycation end products in conventional and extended haemodialysis and haemodiafiltration.

Protein-bound uraemic toxins (PBUT), dicarbonyl stress and advanced glycation end products (AGEs) associate with cardiovascular disease in dialysis. Intensive haemodialysis (HD) may have significant clinical benefits. The aim of this study was to evaluate the acute effects of conventional and extended HD and haemodiafiltration (HDF) on reduction ratio (RR) and total solute removal (TSR) of PBUT, dicarbonyl stress compounds and AGEs. Thirteen stable conventional HD patients randomly completed a single study of 4-h HD (HD4), 4-h HDF (HDF4), 8-h HD (HD8) and 8-h HDF (HDF8) with a 2-week interval between the study sessions. RR and TSR of PBUT [indoxyl sulphate (IS), p-cresyl sulphate (PCS), p-cresyl glucuronide, 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3-acetic acid (IAA) and hippuric acid] of free and protein-bound AGEs [N(ε)-(carboxymethyl)lysine (CML), N(ε)-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine, pentosidine], as well as of dicarbonyl compounds [glyoxal, methylglyoxal, 3-deoxyglucosone], were determined. Compared with HD4, HDF4 resulted in increased RR of total and/or free fractions of IAA and IS as well as increased RR of free CML and CEL. HD8 and HDF8 showed a further increase in TSR and RR of PBUT (except CMPF), as well as of dicarbonyl stress and free AGEs compared with HD4 and HDF4. Compared with HD8, HDF8 only significantly increased RR of total and free IAA and free PCS, as well as RR of free CEL. Dialysis time extension (HD8 and HDF8) optimized TSR and RR of PBUT, dicarbonyl stress and AGEs, whereas HDF8 was superior to HD8 for only a few compounds.

Influence of high-flux hemodialysis and hemodiafiltration on serum C-terminal agrin fragment levels in end-stage renal disease patients

C-terminal agrin fragment (CAF, 22kDa) has been shown to be a promising new rapid biomarker for kidney function. This study evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) treatment on serum CAF concentrations in patients with end-stage renal disease (ESRD). A total of 36 patients with ESRD undergoing chronic HD/HDF treatment were enrolled (21 high-flux-HD/Fx60 membrane, 7 high-flux-HD/Elisio19H membrane, and 8 HDF/Elisio19H membrane). On a midweek session, blood samples were obtained before, at halftime, and post-treatment. Dialysate samples were obtained 4 times during treatment. Serum and dialysate CAF, cystatin C, urea, and creatinine concentrations were measured. Reduction ratios (RRs), totalsolute removal, overall dialytic clearance, and instantaneous dialytic clearance at halftime were calculated and compared. Although HD/Elisio19H and HDF/Elisio19H treatments significantly reduced CAF concentrations (RR 46.6±9.1% and 57.6±11.7%, respectively, P=0.018 and P=0.001), HD/Fx60 treatment did not remove CAF from serum (RR 2.4±15.4%, P=0.25), there was no relevant CAF detection in dialysate. In the HD/Fx60 group, the RR of CAF was significantly lower compared with cystatin C, urea, and creatinine, in which significant removal was detected (37.9±14.8%, 65.0±10.7%, and 56.0±9.8%, respectively, P<0.001). CAF is a new biomarker for kidney function whose serum concentration is not influenced by conventional high-flux HD using Fx60 membrane. It might therefore represent a promising dialysis-independent biomarker for evaluation of kidney function, for example, in acute kidney failure.

Evaluation of Alternatives for Dysfunctional Double Lumen Central Venous Catheters Using a Two-Compartmental Mathematical Model for Different Solutes

Double lumen (DL) central venous catheters (CVC) often suffer from thrombosis, fibrin sheet formation, and/or suction towards the vessel wall, resulting in insufficient blood flow during hemodialysis. Reversing the catheter connection often restores blood flows, but will lead to higher recirculation. Single lumen (SL) CVCs have often fewer flow problems, but they inherently have some degree of recirculation. To assist bedside clinical decision making on optimal catheter application, we investigated mathematically the differences in dialysis adequacy using different modes of access with CVCs. A mathematical model was developed to calculate reduction ratio (RR) and total solute removal (TSR) of urea, methylguanidine (MG), beta-2-microglobulin (β2M), and phosphate (P) during different dialysis scenarios: 4-h dialysis with a well-functioning DL CVC (DL-normal, blood flow QB 350 ml/min), dysfunctional DL CVC (DL-low flow, QB 250), reversed DL CVC (DL-reversed, QB 350, recirculation R = 10%) and 12 Fr SL CVC (effective QB 273). With DL-normal as reference, urea RR was decreased by 3.5% (DL-reversed), 13.0% (SL), and 15.6% (DL-low flow), while urea TSR was decreased by 3.3% (DL-reversed), 13.2% (SL), and 13.5% (DL-low flow). The same trend was found for MG and P. However, β2M RR decreased only 1.5% with SL CVC although TSR decrease was 17.2%, while RR decreased 21.1% with DL-low flow although TSR decrease was only 4.9%. In the case of dysfunctional DL CVCs, reversing the catheter connection and restoring the blood flow did not impair TSR, with 10% recirculation. The SL CVC showed suboptimal TSR results that were similar to those of the dysfunctional DL CVC.

Slow Extended Nocturnal Home Hemodialysis Shows Superior Adequacy Compared to In-Center Dialysis: A Mathematical Analysis

Extended nocturnal home hemodialysis has gained renewed interest. However, no removal data for single/double needle (lumen) (SL and DL, respectively) or for low/high blood flow in extended dialysis are available. Therefore, we studied dialysis adequacy in different nocturnal home hemodialysis strategies. Coupling a kinetic with a dialyzer model, we calculated a reduction ratio from pre- to post-dialysis (RR) and total solute removal (TSR) of urea, methylguanidine (MG), β₂-microglobulin, and phosphate. Simulations were done for dialysis with blood flow Q_b350 ml/min (DL-4h), extended DL high flow with Q_b350 (DL-HF-8h) and low flow with Q_b175 (DL-LF-8h), and SL with Q_b273 (SL-8h). Compared to DL-4h, TSR was 28–59% larger for DL-HF-8h. TSR was most increased for β₂-microglobulin (18%) with DL-LF-8h, and for MG (35%) with SL-8h. Furthermore, RRs were equal (DL-LF-8h), higher (SL-8h), and even more increased (DL-HF-8h) for all studied solutes. In the home setting, DL-LF-8h and SL-8h are safe and promising strategies.

Removal of water-soluble and protein-bound solutes with reversed mid-dilution versus post-dilution haemodiafiltration

Convective dialysis strategies are superior in the removal of protein-bound uraemic retention solutes. Mid-dilution and mixed-dilution haemodiafiltration (HDF), both combining pre-dilution and post-dilution, are promising options to further improve removal capacity and have been shown of additional benefit for large middle molecules. In this study, we compared the removal of small water-soluble and protein-bound solutes in post-dilution versus mid-dilution HDF. Fourteen chronic haemodialysis (HD) patients were included in this crossover study. Patients were kept for 4 weeks on high-flux HD. On the mid-week session of Weeks 3 and 4, either post-dilution or reversed mid-dilution HDF were applied, in random order. Blood and dialysate flows were maintained at 300 and 800 mL/min, while the substitution flow was 75 mL/min in post-dilution and 150 mL/min in mid-dilution HDF. Based on the data collected during the sessions under study, extraction ratio (ER) and reduction ratio (RR) of small water-soluble and protein-bound solutes were calculated, as well as total solute removal (TSR) based on spent dialysate. No differences were observed for TSR, ER and RR for protein-bound solutes. For small water-soluble solutes, ER in post-dilution HDF was significantly higher than in mid-dilution HDF: 0.92 ± 0.02 versus 0.87 ± 0.04 for urea (P < 0.001), 0.92 ± 0.02 versus 0.88 ± 0.02 for creatinine (P < 0.001) and 0.84 ± 0.02 versus 0.82 ± 0.03 for uric acid (P = 0.009). TSR and RR were, however, not different due to the lower inlet concentrations with post-dilution HDF. TSR of mid-dilution and post-dilution HDF was not different for both small water-soluble and protein-bound compounds. Both strategies in the setting as applied in this study are as adequate for the removal of these solutes.

Reduction in Protein-Bound Solutes Unacceptable as Marker of Dialysis Efficacy during Alternate-Night Nocturnal Hemodialysis

Background: The uremic retention solutes indoxyl sulfate and p-cresyl sulfate are linked to cardiovascular disease and overall survival. Dialytic clearances are limited, which is principally attributed to tight protein binding. Extending dialysis duration would be expected to substantially increase protein-bound uremic solute removal. The aim of the current study was to study protein-bound uremic retention solute clearances and kinetics during longer-hours nocturnal hemodialysis. Methods: In a prospective cohort study of 32 maintenance alternate-night nocturnal hemodialysis patients, we followed serum concentrations, solute removals and solute clearances of p-cresyl sulfate and indoxyl sulfate. Spent dialysate sampling was fractionated to compare solute removals between the first 4 h and next 4 h of nocturnal dialysis. Single-compartment variable volume kinetics were calculated. Results: Dialytic clearances of protein-bound uremic retention solutes are maintained during nocturnal (longer-hours) dialysis. Clearances of indoxyl sulfate exceed those of p-cresyl sulfate, presumably due to less tight protein-binding. Apparent distribution volumes increase substantially during nocturnal dialysis, indicative of multi-compartmental behavior of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. Conclusions: During nocturnal hemodialysis, serum concentrations of protein-bound solute concentrations are reduced less than predicted. Reduction ratios are not a valid tool to estimate total solute removal of protein-bound uremic retention solutes.

Influence of switching connection ports of double-lumen permanent tunnelled catheters on total solute removal during dialysis

Catheter dysfunction is a concern when using double-lumen catheters in hemodialysis (HD). Reversing the connection mode results in higher blood flows, but also enhanced recirculation. We evaluated total solute removal (TSR) of different uremic retention solutes during a complete HD session, once with reversed (RL) and once with correctly connected lines (CL). Genius dialysis was performed in 22 HD patients at maximum blood flow (QB), once with CL and once with RL. TSR was determined for urea, creatinine, phosphate and ß2-microglobulin (ß2M). Using a kinetic model, we simulated TSR and reduction ratio (RR) for urea for different percentages of access recirculation and different QB during CL vs. RL. RR and TSR of the tested solutes were not different in clinical practice between CL and RL. Mathematically, urea RR did not differ with CL or RL, but TSR decreased by 4.5%-23.3% when changing from CL to RL for a recirculation of 5%-25%, respectively. For a recirculation of 5%-25%, QB in RL should be increased by 6.7% and 52.0%, 8.5% and 72.0%, and 10.0% and 115.2%, respectively, for a blood flow in CL mode of 150, 200 or 250 ml/min. Connecting patients to double-lumen dialysis catheters in RL does not impair TSR in clinical practice. Mathematically, TSR during RL was dependent upon the obtained QB and degree of recirculation. A nomogram indicating the increase in QB needed in RL to obtain equal TSR as in the CL mode, at different degrees of recirculation, is provided.

Complementary parameter for dialysis monitoring based on UV absorbance

An optical on-line monitoring system aimed at the estimation of dialysis dose has been tested clinically. The natural logarithmic slope is used to calculate Kt/V(urea) from ultraviolet (UV)-absorbance measurements. Errors in the calculation of Kt/V(urea) may appear due to changes in blood and dialysate flow or due to disturbances when the slope is used to estimate dialysis dose. This study introduces a new parameter for dialysis monitoring that may be used as a complementary parameter, the area under UV-absorbance curve (AUCa), to reflect a total solute removal during dialysis. The aim was to investigate the relationship between this new dialysis on-line monitoring parameter, AUCa, and the total removal of a few solutes. Fifteen patients were monitored during hemodialysis using UV absorbance at the wavelength of 297 nm. All spent dialysate passed through a flow cuvette in a spectrophotometer and then further to a collection tank where solute concentrations in the entire spent dialysate were determined. The AUCa at 297 nm was compared with the total amount of removed solute in the tank (reference method). The result shows strong correlations between AUCa and the total removal of urea, urate, creatinine, and phosphate during a given treatment and less strong correlation in all 15 patients together. A first indication of a new, possible, complementary parameter in hemodialysis treatment is presented, the AUCa, prospected to estimate solute removal.

Benefits of preserving residual renal function in peritoneal dialysis

Residual renal function (RRF) is of paramount importance in patients with end-stage renal disease, with benefits that go beyond contributing to achievement of adequacy targets. Several studies have found that RRF rather than overall adequacy (as estimated from total small solute removal rates) is an essential marker of patient and, to a lesser extent, technique survival during chronic peritoneal dialysis (PD) therapy. In addition, RRF is associated with a reduction in blood pressure and left ventricular hypertrophy, increased sodium removal and improved fluid status, lower serum beta(2)-microglobulin, phosphate and uric acid levels, higher serum hemoglobin and bicarbonate levels, better nutritional status, a more favorable lipid profile, decreased circulating inflammatory markers, and lower risk for peritonitis in PD. As compared with conventional hemodialysis, PD is associated with a slower decrease in RRF. This highlights the usefulness of strategies oriented to preserve both RRF and the long-term viability of the peritoneal membrane. Several factors contributing to the loss of RRF have been identified and should be avoided. Renoprotective drugs and new glucose-sparing, more biocompatible PD regimes may prove useful tools to preserve RRF and peritoneal membrane function in the near future.

Impact of hemodialysis duration on the removal of uremic retention solutes

Several studies have stressed the importance of dialysis time in the removal of uremic retention solutes. To further investigate this, nine stable chronic hemodialysis patients were dialyzed for 4, 6, or 8 h processing the same total blood and dialysate volume by the Genius system and high-flux FX80 dialyzers. Inlet blood and outlet dialysate were analyzed for urea, creatinine, phosphorus, and beta2-microglobulin at various times. Total solute removal, dialyzer extraction ratios, and total cleared volumes were significantly larger during prolonged dialysis for urea, creatinine, phosphorus, and beta2-microglobulin. Reduction ratios increased progressively, except for phosphate and beta2-microglobulin, where the ratios remained constant after 2 h. In contrast, no significant difference was found for the reduction ratios of all solutes and Kt/V(urea) between the three different sessions. With longer dialyses, solutes are efficiently removed from the deeper compartments of the patient's body. Our study shows that care must be taken when using Kt/Vurea or reduction ratios as the only parameters to quantify dialysis adequacy.

Differences in solute removal by two high-flux membranes of nominally similar synthetic polymers

Membranes fabricated from nominally similar polymers may be markedly different in chemical composition, morphology and geometry. To examine the relative importance of these factors to dialyzer performance, the removal of small and large uraemic toxins was determined for dialyzers containing 'polysulfone' membranes of different composition and morphology, with and without fibre undulations. Total removal and instantaneous clearances of urea, phosphorus, beta(2)-microglobulin, leptin, angiogenin, complement factor D and immunoglobulin kappa light chain were determined in randomized cross-over studies. Total solute removal was assessed from the pre- to post-dialysis change in plasma concentration and the total amount of solute recovered in the dialysate. Trapping of solute at the membrane was determined as the difference between solute lost from plasma water and solute recovered in the dialysate. Total removal of urea and phosphorus was independent of the membrane composition and structure. Large molecule removal differed significantly between the two membranes, particularly for beta(2)-microglobulin. The importance of trapping at the membrane as a mechanism of beta(2)-microglobulin removal also differed significantly between the two membranes, with trapping being less important for the membrane with the greatest beta(2)-microglobulin removal. As molecular size increased, the contribution of trapping at the membrane to solute removal increased and the difference between the two membranes decreased. High-flux membranes fabricated from nominally similar polymers may differ significantly in their ability to remove low molecular weight protein uraemic toxins.

SOLUTE CLEARANCE DURING CRRT: ANALYSIS WITH A FINITE ELEMENT MODEL

We developed a finitite element model (FEM) of a hollow fiber to simulate CVVHD, including blood and dialysate flow, ultrafiltration, internal filtration/backfiltration (IF/BF), convection-diffusion interaction, and concentration polarization. We simulated conditions of postdilution CVVHD for urea and vitamin B12 flux in a AN69 hollow fiber dialyzer. We conducted the following analyses: 1) Determination of the total solute removal when substitution/dialysate (S/D) fluid was varied from pure hemofiltration to pure hemodialysis, 2) comparison of CVVH and CVVD to evaluate efficiency of convective vs. diffusive flux, and 3) evaluate the contribution of IF/BF. The efficiency in urea removal was inversely related to the ratio of dialysate to substitution fluid. Clearance during CVVD was less than CVVH with increasing total S/D infusion, thus CVVH is more efficient than CVVD at the same flow rates. Hemofiltration with 6 L/min substitution fluid in CVVH resulted in 51% more total clearance than 6 L/min dialysate in CVVD. At 1 L/min, however, CVVH only afforded a 4% increase in total clearance. Under zero net ultrafiltration, IF/BF accounted for only 0.45% and 0.47% of total clearance for urea and B12 despite differences in diffusivity and sieving coefficients. FEM allows evaluation of CRRT performance, including quantitation of convective and diffusive fluxes, and flux during IF/BF. Our findings suggest that CVVH is considerably more efficient than CVVHD at high but not traditional volumes. Clearance from IF/BF contributes less than 0.5% of total clearance under traditional dialyzer design.

A fractional dialysate collection method to estimate solute removal in continuous venovenous hemodialysis

Fractional direct dialysis quantification (fDDQ), whereby a known proportion of dialysate effluent is sampled, can reliably estimate total solute removal in intermittent hemodialysis (IHD). Our study aimed to develop and test the technique in continuous venovenous hemodialysis (CVVHD). Twenty dialysate collections (mean duration 23.5 hours, range 17.25 to 26.6) were performed in 12 patients on CVVHD. An infusion pump diverted 10% of the total effluent volume to the fractional collection (fc), the remainder being channeled into the bulk collection (bc). Both fc and bc were collected on ice and assayed for urea nitrogen (UN) and creatinine (Cr). Actual solute removal (ASR) was calculated from the measured effluent volume and solute concentrations of the fc and bc. Estimated solute removal (ESR) was calculated from the product of the fc solute concentration and effluent volume. All fc/bc samples in 15 out of 20 collections underwent gram stain and aerobic/anaerobic culture. Bland-Altman analyses suggested good agreement between ASR and ESR [absolute values of percentage differences: 95% CI = 1.73, 5.17% (UN); 1.88, 4.31% (Cr)]. Favorable concordance correlation coefficients confirmed this [rc = 0.995 (UN), 0.997 (Cr)] and were apparently unaffected by heavy pseudomonal growths in 4 out of 7 culture positive collections [rc = 0.997 (UN), 0.997 (Cr); culture negative (N = 8), rc = 0.996 (UN), 0.997 Cr)]. fDDQ, using 24-hour, pump-assisted, cooled fractional dialysate sampling reliably estimates total solute removal and provides a practical alternative to total dialysate collection in assessing delivered dialysis dose.

Fractional direct dialysis quantification: A new approach for prescription and monitoring hemodialysis therapy

We describe a new methodology, fractional direct dialysis quantification (FDDQ) utilizing the Fresinius Dialysate Sampling Module (DSM), for quantitating total solute removal during hemodialysis (HD). Our data demonstrate that this technique and Direct Dialysis Quantification (DDQ) yield virtually identical results. FDDQ, however, obviates the practical obstacles that have limited the applicability of DDQ. We discuss the theoretical and practical advantages of this methodology, as compared to urea kinetic modeling (UKM) with Kt/V, for prescribing and monitoring dialysis therapy. FDDQ provides reliable and accurate quantitative data of dialysis function and protein catabolic rate (PCR) independent of questionable theoretical assumptions and parameters required for UKM with Kt/V. It is simple to comprehend and apply. It permits easy comparison of standard and rapid high efficiency dialyses. It also facilitates the quantitative comparison of HD and continuous therapies (peritoneal dialysis and various types of continuous hemofiltration). FDDQ permits the use of other solutes, in place of or in addition to urea, for the quantitation of HD. Because of its simplicity and probable low cost, it can be used with each HD session. It will thus provide accurate data on delivered versus prescribed therapy. These features should permit more accurate monitoring and lead to a clearer understanding of the relationship of outcomes versus delivered dialysis dose, and consequently more effective adjustment of dialysis therapy.

Evaluation of peritoneal membrane permeability.

Total removal of fluid and solutes during peritoneal dialysis depends on both the dialysis prescription (ie, the number, length, and timing of the dwells and the volume and contents of the dialysis solution) and the permeability of the peritoneal membrane. Peritoneal membrane permeability determines the rate of solute equilibration between body fluids and the solution within the peritoneal cavity and is, therefore, a significant determinant of the solute removal rate. The relationship between fluid removal during peritoneal dialysis and the properties of the peritoneal membrane is more complex; peritoneal ultrafiltration is inversely related to the permeability of the peritoneal membrane to osmotic solutes but is directly related to the hydraulic conductivity of the peritoneal membrane. The peritoneal equilibration test (PET) is widely used as the standard method for evaluating peritoneal membrane permeability, and results from the PET can be used to determine the type of peritoneal dialysis therapy optimal for the permeability characteristics of the patient's peritoneal membrane. Simple extrapolations from the PET can only provide qualitative estimates of the dialysis dose required for various types of peritoneal dialysis. More accurate estimates of the required dialysis dose can be provided by mathematical models of peritoneal fluid and solute transport, but these models require calculation of the permeability-area product or mass transfer-area coefficient of the peritoneal membrane. Although the latter approach shows promise for improving peritoneal dialysis prescriptions, determination of the delivered dose of peritoneal dialysis can, at present, only be assessed by directly measuring total 24-hour solute and fluid removal.