Comparison of middle-molecule clearance between convective control double high-flux hemodiafiltration and on-line hemodiafiltration

Hemodiafiltration (HDF) is now a well-recognized treatment modality for end-stage renal disease (ESRD) patients. It provides superior characteristics over conventional hemodialysis in many respects. On-line HDF, however, which has been mainly used in clinical practice, requires a special machine. Interestingly, the recently innovated convective-control double high-flux hemodiafiltration (CC-DHF) machine can provide HDF treatment with an adjustable convection rate by using the conventional volume-controlled dialysate flow hemodialysis machine in a modified way. The present study was conducted to compare the efficacy of CC-DHF compared to on-line HDF in terms of middle and small solute clearances in 12 stable, chronic hemodialysis patients who underwent hemodialysis three times a week for at least 6 months. The results showed that the beta 2-microglobulin (beta 2M) removal represented by the beta 2M clearance in CC-DHF was comparable to that in on-line HDF (112.4+/-17.0 vs. 119.4+/-15.5 ml/min respectively, NS). Also, the beta 2M reduction ratio in the CC-DHF group did not differ from the on-line HDF group (85.5+/-4.2% vs. 86.1+/-6.7%, NS). With regard to small solute clearances, the values of single-pool Kt/V and phosphate clearance did not differ between CC-DHF and on-line HDF groups. In conclusion, CC-DHF provides removal of beta 2M and small molecule uremic toxins that is comparable to on-line HDF. An on-line HDF machine may not be available in all hemodialysis centers, whereas CC-DHF can be easily set up, with proper precautions regarding the fluid quality. Therefore, CC-DHF can provide the benefits of convective therapy to patients in situations where use of an on-line HDF machine is limited.     

Leptin and beta2-microglobulin kinetics with three different dialysis modalities

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Beta2-microglobulin clearance with super high flux hemodialysis: an ex vivo study

BACKGROUND: Beta2m accumulation induces disease in patients with end-stage renal failure (ESRF). Thus, its removal from patients with ESRF appears desirable. Current dialysis technology, however, has limited effectiveness. AIMS: To measure beta2m clearance with a novel super high flux membrane. DESIGN: Ex vivo experimental study. SETTING: Intensive Care Laboratory of Tertiary institution. SUBJECTS: Six volunteers. MEASUREMENTS AND RESULTS: At a blood flow of 300 ml/min, the clearance of beta2-MG increased from 113.5 +/- 38.5 ml/min with a dialysate flow rate of 200 ml/min to 184.8 +/- 61.1 ml/min with a flow rate of 300 ml/min and 195.0 +/- 60.0 ml/min with a 500 ml/min flow rate. The clearance of albumin was 4.5 ml/min with a dialysate flow rate of 200 ml/min, 5.2 ml/min for a flow rate of 300 ml/min and 5.8 ml/min for a flow rate of 500 ml/min. CONCLUSIONS: High levels of beta2m clearance can be achieved with a super high flux membrane while albumin losses remain limited.     

Effects of internal filtration on the solute removal efficiency of a dialyzer

To improve solute removal efficiency, several types of dialyzers with enhanced internal filtration were introduced for clinical application. In these dialyzers, enhanced internal filtration increased convective transport of the solute, in addition to diffusive transport. In this study, the effects of internal filtration on solute removal efficiency were examined by both analytic and experimental studies. Internal filtration is affected by blood (Q(B)) and dialysate (Q(D)) flow rates; the patient's hematocrit and plasma level of total protein; and the effective length (L(eff)), inner diameter (D), and density ratio (DR) of the hollow fibers. An analytic model was introduced for the estimation of the changes in mass and momentum along the dialyzer. It clarified the effects of these parameters on maximum internal filtration flow rate (Q(IF)) and clearance (K) of urea (60 daltons), vitamin B(12) (1,355), and myoglobin (17,000). As a result of the analytic study, Q(IF) was increased, resulting in a smaller D, a longer L(eff), and a larger DR value. Several types of dialyzers with the same cellulose triacetate membrane, produced by Toyobo Co, Ltd., Ohtsu, Japan, and Nissho Corporation, Kusatsu, Japan, were used for the experimental study. An in vitro evaluation using myoglobin solution showed the same trends as found in the analytic study. For example, a dialyzer with 150 microm of D has a 72.0 ml/min myoglobin K value, much higher than that of 53.7 ml/min for a dialyzer with 200 microm of D under constant Q(B) (300 ml/min) and DR (50%) values. Development of a dialyzer with enhanced internal filtration, however, should take the patient's safety into account, and hemolysis and endotoxin invasion from the dialysate to the patient should be avoided.     

Hemodiafiltration without replacement fluid. An experimental study.

Paired filtration dialysis (PFD) is the only hemodiafiltration (HDF) technique in which the ultrafiltrate is continuously available but not mixed with the dialysate. As is the case during all convective or predominantly convective techniques, use of a replacement fluid is necessary in an amount equal to the difference between the ultrafiltrate and the desired patient weight loss. This replacement fluid must have an adequate electrolytic composition (Na+, Ca++, and buffer), and must be sterile and pyrogen free. Using an uncoated adsorbent charcoal cartridge (130 g), the ultrafiltrate obtained in PFD was regenerated, eliminating both the small (except for urea, glucose, and phosphates) and medium-to-large solutes but not the electrolytes and bicarbonate. This verified the ultrafiltrate's possible use as replacement fluid. This technique experimentally studied during 24 standard PFD sessions, with a total mean ultrafiltrate of 9,950 +/- 860 ml, allowed a replacement solution to be obtained with the following mean +/- SD composition: pH 7.467 +/- 0.122, HCO3- 27.0 +/- 2.12 mmol/L, Na+ 137.4 +/- 2.6 mmol/L, K+ 4.1 +/- 0.83 mmol/L, Ca++ 1.12 +/- 0.19 mmol/L, urea 68.3 +/- 16.2 mg/dl, creatinine 0.08 +/- 0.02 mg/dl, uric acid 0.05 mg/dl, phosphates 2.77 +/- 0.71 mg/dl, beta-2 microglobulin 0.5 +/- 0.4 mg/L, and atrial natriuretic peptide 4.41 +/- 5.6 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Albumin loss in on-line hemodiafiltration

BACKGROUND: Based on the increased hydraulic permeability of the new high permeability polyethersulfone membrane, DIAPES HF-800, we investigated the kinetics and handling of albumin in high volume on-line hemodiafiltration (HDF). METHODS: Seven patients on predilutional HDF were studied in two consecutive sessions. Blood flow rate and transmembrane pressure were continuously monitored. Spent dialysate was spilled at 20 ml/h every hour. Albumin was measured in blood and dialysate by immunonephelometry. Albumin and proteins adsorbed onto the dialyzer membrane were eluted after treatment with Triton X. Ultrafiltrates collected at 1 and 2 hours of treatment were pooled from different patients and incubated for 24 hours at 37 degrees C with bovine serum albumin (BSA). Total sulphydryl groups were evaluated using Ellmann's reagent [5, 5'-dithio-bis(2-nitrobenzoic acid)]. RESULTS: In all 7 patients, the total loss of albumin was 3.99 +/- 1.81 g, ranging between 1.09 and 6.82 g/session. Most albumin loss occurred in the first 60 min of pre-dilutional hemodiafiltration (1.92+0.83 g). There was no correlation between transmembrane pressure, urea clearance and the loss of albumin. Plasma water urea clearance values were stable over the treatment (234 +/- 14.3 ml/min). Plasma albumin concentration did not decrease during HDF sessions. Albumin adsorbed onto the dialyzers was 0.7 +/- 1.6 mg but the total amount of adsorbed proteins was much higher (130 + 90 mg). In addition, the ultrafiltrate collected during HDF sessions was able to induce oxidation of bovine serum albumin as measured by total protein sulfhydryl groups: bovine serum albumin incubated in the presence of ultrafiltrate collected at 1 hour had a sulfhydryl loss of 56.3 +/- 5.7% (p < 0.0001 vs control), and bovine serum albumin incubated with ultrafiltrate collected at 2 hours had a loss of 67.5 +/- 3.8% (p < 0.003 vs control). CONCLUSION: The present study shows the high inter- and intra-patient variability of transmembrane passage of albumin in chronically uremic patients undergoing pre-dilutional HDF. Factors involved do not seem to be correlated to transmembrane pressure but rather to an interaction with the polymer surface. Albumin adsorption was minimal and was significantly lower than that of other plasma proteins. Albumin loss during HDF seemed to have no acute impact on plasma albumin. In addition, we demonstrated the presence of prooxidative compounds able to oxidize albumin, of which extracorporeal removal by HDF procedure could be beneficial for HD patients.     

Development of a dialyzer with enhanced internal filtration to increase the clearance of low molecular weight proteins

Accumulated low molecular weight proteins in hemodialysis patients require a high-flux dialyzer. There have been several methods proposed for enhancing internal filtration, including narrowing the inside diameter of the hollow fibers, lengthening the fibers, and increasing the fiber density ratio. We tried to enhance the internal filtration by increasing the pressure drop in the dialysate compartment through increasing the fiber density ratio. If the fiber density ratio is too high, however, an irregular dialysate path may result, thus decreasing dialysis performance. Therefore, we took note of the shape of the inner housing and added a short taper structure, which improved the dialysate path dramatically. Consequently, we developed an internal filtration-enhanced dialyzer (APS-Prototype) to improve dialysis performance. The internal filtration rate in water (measured by Doppler ultrasound) was 13.2l/session for the APS-Prototype and 5.3l/session for the APS-15E. The amount of 1-microglobulin (1-MG) in bovine plasma was 0.34g for the APS-Prototype and 0.11g for the APS-15E. In addition, the amount of 1-MG in vivo was 29.0% ± 5.8% for the APS-Prototype, significantly higher than that for the APS-15E (13.6% ± 1.9%). The desirable loss of albumin is 2–4g in hemodiafiltration, and it was 3.92 ± 1.03g for the APS-Prototype. The prototype showed excellent solute removal performance with no clinical or engineering problems.     

Membrane fouling and dialysate flow pattern in an internal filtration-enhancing dialyzer

For efficient removal of large molecular weight solutes by dialysis, several types of internal filtration-enhancing dialyzers (IFEDs) are commercially available. However, in a pressure-driven membrane separation process (i.e., filtration), membrane fouling caused by adhesion of plasma proteins is a severe problem. The objective of the present study is to investigate the effects of internal filtration on membrane fouling based on the membrane's pure-water permeability, diffusive permeability, and sieving coefficient. Hemodialysis experiments were performed with two different dialyzers, IFEDs and non-IFEDs. Local membrane fouling in each dialyzer was evaluated by measuring the pure-water permeability, the diffusive permeability, and the sieving coefficient of native membranes and membranes treated with bovine blood. The effects of packing ratio on dialysate flow pattern were also evaluated by measuring the time required for an ion tracer to reach electrodes placed in the dialyzers. In the IFED, membrane fouling caused by protein adhesion is increased because of enhanced internal filtration only at the early stage of dialysis, and this fouling tends to occur only near the dialysate outlet port. However, enhanced internal filtration has little effect on measured membrane transfer parameters.     

Bound solute dialysis

We used the thermodynamic principles governing bound solute dialysis, commonly referred to as "albumin dialysis" or "sorbent dialysis" and practiced clinically with the Molecular Adsorbent Recirculating System (MARS) and Biologic-DT approaches, respectively, to develop a comprehensive understanding of the process. Dimensionless parameters emerging from the thermodynamic analysis that govern bound solute dialysis are as follows: (1) lambda, the binding power of the solute binding moiety; (2) kappa, the dialyzer mass transfer/blood flow rate ratio; (3) alpha, the dialysate/blood flow rate ratio; (4) beta, the dialysate/blood binding moiety concentration ratio, and (5) psi, the solute/binding moiety concentration ratio in the blood. Results from a mathematical model of countercurrent bound solute dialysis for phi = 0.9 indicate that for a given binding moiety (fixed lambda), the most important parameter for achieving high removal rates is the dialyzer mass transfer ratio for free (unbound) solute. The results also show solute removal approaching an asymptote with increasing beta that is dependent on kappa and independent of alpha. More importantly, results indicate that once a dialysis membrane is chosen, solute removal is virtually independent of blood flow rate, dialysate flow rate, and amount of binding moiety in the dialysate, provided the amount is greater than approximately 90% of that required to reach the asymptote. Experimental observations over a range of blood flow rates (100-400 ml/ minute), dialysate flow rates (50-400 ml/minute), and dialysate/blood albumin concentration ratios (beta = 0-0.3) corroborate the model predictions and indicate that < 4 g/L albumin in the dialysate solution is required for effective bound solute dialysis. The experimental results also show evidence of enhanced mass transfer once the dialysis membrane pore structure surface saturates with albumin.     

Filtration of dialysate using an on-line dialysate filter.

Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. In conclusion: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.     

Super high flux hemodialysis at high dialysate flows: an ex vivo assessment

BACKGROUND AND OBJECTIVES: The removal of cytokines by standard hemofiltration is limited. Super high flux membranes may significantly improve removal even when used in dialysis mode. We sought to measure cytokine clearance using a large surface super high-flux membrane and a standard hemodialysis setting. SETTING: ICU laboratory of a tertiary institution. SUBJECTS: Six healthy volunteers. METHODS: Blood form healthy volunteers was incubated for 4 hours with E. coli endotoxin to stimulate cytokine production. Cytokine containing blood was then circulated through a dialysis circuit at 3 different dialysate flow rates. Blood and dialysate were sampled for cytokine and albumin measurements and calculation of clearances. RESULTS: Super high-flux dialysis achieved high median cytokine clearances (IL-1 clearance of 106 ml/min, IL-6 clearance of 66.8 ml/min, IL-8 clearance of 61.7 ml/min and TNF clearance of 36.1 ml/min). Increasing dialysate flow rate from 300 to 500 ml/min did not significantly increase cytokine clearances. Albumin clearances however were between 2.7 and 5.4 ml/min. CONCLUSIONS: Cytokine dialysis is feasible at high dialysate flow rates yielding high cytokine clearances. Albumin loss, however, is appreciable and may require separate supplementation in the clinical setting.     

Low-volume continuous hemodiafiltration with nafamostat mesilate increases trypsin clearance without decreasing plasma trypsin concentration in severe acute pancreatitis

Continuous hemodiafiltration (CHDF) has recently been used for treatment of severe acute pancreatitis. CHDF is capable of eliminating small molecules from blood, but whether trypsin can be eliminated by CHDF is not clear. In this study, elimination of trypsin-like enzyme activity (TLE) and cationic trypsin-like immunoreactivity (TLI) using low-volume CHDF was examined at the first CHDF session in eight patients with severe acute pancreatitis. CHDF was performed with a polysulfone hemofilter (membrane area, 0.7 m2) and nafamostat mesilate, a protease inhibitor and anticoagulant, at a blood flow rate of 100 ml/min and a filtration and dialysis flow rate of 10 ml/min each. Before beginning CHDF, plasma TLE was 3.41 +/- 2.86 nmol/(ml.min), and TLI was 5,900 +/- 9,008 ng/ml. The average plasma clearances of TLE and TLI achieved by the circuit during the 12-hour therapy were 56.7 +/- 4.9 ml/min and 8.0 +/- 7.2 ml/min, respectively. The average plasma clearance of TLI into the waste fluid was 2.4 +/- 1.6 ml/min whereas TLE was below the measurable sensitivity. The plasma concentration of TLE and TLI remained unchanged. These results indicate that low-volume CHDF using nafamostat mesilate as an anticoagulant can increase trypsin plasma clearance. However, low-volume CHDF is not effective to eliminate the plasma trypsin concentration.     

Slow continuous ultrafiltration with bound solute dialysis

Bound solute dialysis (BSD), often referred to as "albumin dialysis" (practiced clinically as the molecular adsorbents recirculating system, MARS, or single-pass albumin dialysis, SPAD) or "sorbent dialysis" (practiced clinically as the charcoal-based Biologic-DT), is based upon the thermodynamic principle that the driving force for solute mass transfer across a dialysis membrane is the difference in free solute concentration across the membrane. The clinically relevant practice of slow continuous ultrafiltration (SCUF) for maintenance of patients with liver failure is analyzed in conjunction with BSD. The primary dimensionless operating parameters that describe SCUF-BSD include (1) beta, the dialysate/blood binder concentration ratio; (2) kappa, the dialyzer mass transfer/blood flow rate ratio; (3) alpha, the dialysate/blood flow rate ratio; and, (4) gamma, the ultrafiltration/blood flow rate ratio. Results from mathematical modeling of solute removal during a single pass through a dialyzer and solute removal from a one-compartment model indicate that solute removal is remarkably insensitive to gamma. Solute removal approaches an asymptote (improvement in theoretical clearance over that obtainable with no binder in the dialysate) with increasing beta that is dependent on kappa and independent of alpha. The amount of binder required to approach the asymptote decreases with increasing solute-binder equilibrium constant, i.e., more strongly bound solutes require less binder in the dialysate. The results of experimental observations over a range of blood flow rates, 100 to 180 mL/min, dialysate flow rates, 600 to 2150 mL/h, ultrafiltration rates, 0 to 220 mL/h, and dialysate/blood albumin concentration ratios, beta = 0.01 to 0.04, were independently predicted remarkably well by the one-compartment model (with no adjustable parameters) based on BSD principles.     

Sequential convective therapies (SCT): a prospective study on feasibility, safety, adequacy and tolerance of on-line hemofiltration and hemodiafiltration in sequence

Sequential dialysis techniques (i.e pure ultrafiltration followed by dialysis) have been used in the past, due to their capability to remove large volumes of fluids without inducing hemodynamic instability. The disadvantages of inadequate efficiency and lack of technology lead to the decline of such methods. Hemofiltration (HF) and hemodiafiltration (HDF) are recently being utilized in a greater proportion thanks to on-line fluid preparation systems. Each process (HF and HDF) has its own benefits in the removal of small, medium and high-molecular weight substances and in hemodynamic stability. Sequential convective therapies (SCT) such as hemofiltration-hemodiafiltration in sequence (HF-HDF) may combine the benefits and eliminate the disadvantages of each method and should be studied in order to explore their potential application in modern dialysis. Furthermore they can be easily applied nowadays, due to the development of new sophisticated dialysis machines. In order to evaluate the feasibility, safety, efficiency and tolerance of different SCT methods we studied 3 schedules: SCT1: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 25% of the total fluid that had to be removed). SCT2: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). SCT3: 2h pre-dilution HF followed by 2h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). We studied 6 chronic hemodialysis patients using the same machine (AK200 ULTRA), with on-line fluid preparation system and the same type of dialyzer (Polyflux 210). SCT schedules were compared to on-line HF, on-line HDF and high flux dialysis performed with the same dialyzers. The treatments resulted safe, easy, feasible and well tolerated with an improved hemodynamic response to high volume convective therapies. Adequacy of treatment was satisfactory in all SCT schedules while middle molecular weight solute clearance and removal resulted higher in treatments with higher convective component. SCT might represent an interesting option for the future especially in patients with hemodynamic instability and requirements for interventions during treatment.     

Cytokine dialysis: an ex vivo study

To test the hypothesis that dialysis using a new large pore membrane would achieve effective cytokine removal, blood from six volunteers was incubated with endotoxin (1 mg) and then circulated through a closed circuit with a polyamide membrane (nominal cut-off: 100 kDa). Hemodialysis was conducted at 1 or 9 L/hr of dialysate flow at the start of circulation and after 2 and 4 hours. The peak dialysate/plasma concentration ratios were 0.92 for interleukin (IL)-1beta, 0.67 for IL-6, 0.94 for IL-8, 0.33 for tumor necrosis factor (TNF)-a, and 0.11 for albumin. The dialysate/plasma ratios for all cytokines and albumin were decreased with increased dialysate flow from 1 to 9 L/hr (p < 0.05). Clearances for IL-1beta, IL-6, and IL-8, however, were significantly improved with increased dialysate flow (p < 0.01). There was no increase in TNF-a clearance (not significant) and a decrease in albumin clearance (p < 0.01). The peak clearance at 9 L/hr was 33 ml/min for IL-1beta, 19 for IL-6, 51 for IL-8, 11 for TNF-alpha, and 1.2 for albumin. No adsorption of cytokines was observed. We conclude that cytokine dialysis is achievable through a membrane with a high cut-off point with negligible albumin loss. These findings support the technical feasibility of this new approach to blood purification in sepsis.     

Validation of a two-pool model for the kinetics of beta2-microglobulin

Secondary amyloidosis due to beta-2-microglobulin (beta2-m) is a serious long-term complication in patients on regular dialysis therapy. Beta2-m can be considered a middle-molecule marker used to facilitate the assessment of dialysis efficacy. For this purpose, a validated model that calculates characteristic efficacy parameters, such as Kt/V, TAC and generation rate, is needed. There is general agreement that beta2-m-kinetics should be described by a two-pool model, but little has been published to validate such an approach. We measured the beta2-m concentration profiles of eight stable patients during hemodialysis (HD) at the start of treatment, after 30 minutes, after 60 minutes, and every hour until the end. Thereafter they were measured at 10-minute intervals for an hour. The dialyser clearances were determined from the plasma concentrations in front of and behind the dialyser twice during each session - after 1 hour, and 4 hours from the start of treatment. The kinetic parameters of a two-pool model (e.g. the compartment volumes V1 and V2, the mass transfer coefficient K12 and the generation rate G) were determined from the optimal fit of the measured concentration profile. The table below summarises the results by giving the mean and standard deviation for each parameter: [table: see text]. Inter-individual differences in V1/V2 and K12 were high, ranging from 2.5 to 10.0 for V/V2 and from 26 to 140 for K12. Error analysis suggested that these wide ranges were due to the method and that in reality the probable range of V is 25-36% of TBW, of V1/V2 3.5-5.3, and of K12 30-80 ml/min. With standard values for these three parameters (V = 30% of TBW, V/V2 = 4.4 and K12 = 55 ml/m), equal for all patients, and their respective ranges, Kt/W can be calculated with a standard deviation of 13%. Kt/W > 1.2 secures the maximum possible beta2-m removal with three HD treatments a week. CONCLUSIONS: The parameters of a two-pool model of beta2-m kinetics can be derived from concentration profiles obtained under routine dialysis conditions, but accuracy is not completely satisfactory. Similar to the dialysis dose for urea (Kt/Vurea) the dialysis dose for beta2-m (Kt/Vbeta2-m) can be calculated from the pre- and post-dialysis concentrations of beta2-m, body weight, ultrafiltration and dialysis time. Kt/Vbeta2-m > 1.2 secures the maximum possible removal of beta2-m in HD with three sessions per week.     

Use of the ultrafiltrate obtained in two-chamber (PFD) hemodiafiltration as replacement fluid. Experimental ex vivo and in vitro study

PFD (Paired Filtration Dialysis) is the only hemodiafiltration (HDF) technique in which the ultrafiltrate (UF) is continuously available not mixed with the dialysate. As with all convective or prevailingly convective techniques, a replacement fluid is necessary in an amount equal to the difference between the UF and the desired weight loss. This replacement fluid (R) must have an adequate electrolytic balance (Na+, Ca++, and buffer), and must be sterile and pyrogen-free. Using an uncoated adsorbent charcoal cartridge, we "regenerated" the UF obtained in PFD, eliminating the small (except for urea, which was later eliminated by diffusion in the dialyzing section of the PFD system) and the medium-to-large molecules (vit B12 and myoglobin in vitro and beta-2-microglobulin (B2m) and (hANP) in vivo), but not the electrolytes and the endogenous bicarbonate, so as to verify its possible use as R. This technique, experimentally performed in 12 patients under HDF treatment with standard PFD, with a total mean UF of 9650 +/- 875 ml and the use of 130 g of uncoated charcoal, produced a solution with the following composition: Na+ 135.4 +/- 2.4 mmol/l, K+ 3.4 +/- 1.23 mmol/l, Ca++ 1.18 +/- 0.14 mmol/l, HCO3- 26.7 +/- 2.3 mmol/l, phosphates 2.88 +/- 0.81 mg/dl, urea 63 +/- 14 mg/dl, creatinine 0.08 +/- 0.02 mg/dl, uric acid 0.05 +/- 0.0 mg/dl, beta-2 microglobulin 0.5 +/- 0.5 mg/l, and hANP 4.15 +/- 5 pg/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-performance liquid chromatographic determination of cefepime in human plasma and in urine and dialysis fluid using a column-switching technique

A high-performance liquid chromatographic method with UV absorbance was developed for the analysis of cefepime in human plasma and urine, and in dialysis fluid. Detection was performed at 280 nm. The assay procedure for cefepime in plasma involves the addition of an internal standard (cefpirome) followed by treatment of the samples with trichloracetic acid, acetonitrile and dichloromethane. To quantify cefepime in diluted urine (1:20) and in the dialysis fluid, samples spiked with the internal standard (cefpirome) were analysed using a column-switching technique. The HPLC column, Nucleosil C18, was equilibrated with an eluent mixture composed of acetonitrile-ammonium acetate (pH 4). Linear detector responses were observed for the calibration curve standards in the range 0.5 to 100 microg/ml, which spans what is currently thought to be the clinically relevant range for cefepime concentrations in body fluids. The limit of quantification was 0.5 microg/ml in the three matrices. Extraction recoveries proved to be more than 84%. Precision, expressed as %RSD, was in the range 1.5 to 9%. Accuracy ranged from 93 to 105%. This method was used to follow the time course of the concentration of cefepime in plasma, urine and dialysate outlet samples after a 10-min infusion period of 2 g of this drug in patients with acute renal failure undergoing hemodiafiltration.     

A comparison of bicarbonate kinetics and acid-base status in high flux hemodialysis and on-line post-dilution hemodiafiltration

Objectives: To compare bicarbonate kinetics and acid base status in HD and HDF for the same patient; and to investigate the effect of patient physiologic parameters on these kinetics. Methods: In order to monitor HCO3- kinetics during dialysis, acid-base parameters, pH, blood gases partial pressures, and HCO3- concentrations were recorded during 3 regular dialysis (HD) and 3 on-line post-dilution HDF sessions performed on 12 patients, using same dialysis fluid with a 38 mmol/l HCO3- concentration. HCO3- mass transfers through the hemodialyzers membranes and into the patients were continuously calculated during the sessions from HCO3- concentrations, together with HCO3-dialysance. The"apparent" HCO3-gain was calculated by integrating over time the instantaneous mass transfer from dialyzer and re-infusion fluid to the patient. A second method consisted in calculating the patient apparent bicarbonate space (ABS) and HCO3- mass (ABS times plasma concentration) at beginning and end of session. Results: No significant differences were observed between acid base parameters at the end of HD and HDF sessions. In contrast to urea clearances, HCO3- dialysances decayed with time during sessions from 110 to 140 ml/min to about 40 ml/min after one hour. The net HCO3- gain was taken as the difference between final and initial HCO3-masses. This net gain was in average 63% of apparent gain in HD and 74% in HDF. Conclusions: Uremic acidosis was well corrected without risk of alkalosis. An unexpected result was the continuous decay of bicarbonate dialysance both in HD and HDF during runs.     

Laboratory data in chronic dialysis patients]

The principle of prescribing dialysis therapy is treatment of uremic symptoms and morbidity, and adequate therapy to prevent complication of long term dialysis. For this purpose careful measurement and monitoring of various parameters should be done in chronic dialysis patients. We analyzed the laboratory data of 82 patients treated at our dialysis center. We started correction of renal anemia with erythropoietin from 1987, and the mean hematocrit was improved from 24% to 28%. The blood transfusion volume was decreased markedly. There was a significant correlation between plasma alpha-human atrial natriuretic peptide (HANP) levels and the size of the heart. Plasma HANP seems to be a reliable parameter of the so-called dry weight in patients on maintenance dialysis. We analyzed the parameters of bone for the recent four years. Alkaline phosphatase (ALP) and C-PTH increased throughout the duration of dialysis, while bone mineral density (BMD) decreased. Annual changes of sigma GS/D were negatively correlated with ALP and C-PTH. In relation to duration of dialysis, changes of sigma GS/D were less in the group treated for less than 3 years. Nine patients (60% of patients on dialysis more than 10 years) had carpal tunnel syndrome (CTS) with symptoms and signs. Median nerve distal motor latency was positively correlated with the duration of dialysis. The beta 2-microglobulin (beta 2-MG) level of dialysis patients was very high and even though the beta 2-MG level was lowered by hemodiafiltration CTS was not improved.