High-flux Polysulfone Dialyzers Research Articles

MO666INVESTIGATIONS INTO DIFFERENCES AND SIMILARITIES BETWEEN SHORT DAILY HIGH-FLUX HEMODIALYSIS AND SHORT DAILY ON-LINE HEMODIAFILTRATION

Abstract Background and Aims Short daily hemodialysis (SDHD) has improved outcomes observed in conventional thrice-weekly hemodialysis (CHD). Analogously, short daily hemodiafiltration (SDHDF) has also improved outcomes observed in conventional thrice-weekly hemodiafiltration (CHDF). Furthermore, while high-volume CHDF has been proclaimed to be superior to CHD, there have been no studies comparing SDHDF to SDHD. We performed a comparison of clinical, laboratory, echocardiographic and quality of life features in dialysis patients treated by SDHD or SDHDF. Method Twelve patients (mean age 60.8±15.4 years; 7 males; AVF 7, AVG 1, Catheter 4) on regular in-center SDHD program were studied in a longitudinal, prospective, non-randomized, single-subject A-B-A design comparing high-flux SDHD to post-dilution on-line SDHDF. Patients had been for at least 6 months on SDHD (105-150min, 6x/week; SDHD1) and were clinically stable before conversion to SDHDF (105-150min, 6x/week, mean total convective volume of 63.57±5.44 L per week) for 6 months. Following that, all patients were switched back to SDHD for another 6 months (SDHD2). Data were collected at the end of each period. Dialysis parameters throughout the study were matched and set as follows: high-flux polysulfone dialyzers (BBraun Xevonta Hi 23®), blood flow 300–350 mL/min, dialysate flow 500 mL/min and ultra-purified water (Aquaboss heat disinfection osmosis). The results were expressed as mean ± standard deviation. Each patient served as his/her own control. Repeated measures analysis of variance (ANOVA) were used. Results Slightly higher predialysis mean arterial pressure (MAP) levels were observed during SDHDF (102.51±11.28 mmHg) compared to SDHD1 (MAP 95.5±9.82 mmHg, p<0.01) or to SDHD2 (97.61±11.19 mmHg, p=0.03), without significant differences in intradialytic blood pressure variability. Similarly, there was an increase in predialysis hemoglobin levels (Hb) during SDHDF (Hb 12.39±1.2 g/dL), compared to SDHD1 (Hb 11.30±1.09 g/dL, p=0.02) or to SDHD2 (Hb 11.23±1.84 g/dL, p<0.01), although there were no significant differences in erythropoietin-stimulating agent or iron supplementation weekly doses, transferrin saturation rates or ferritin levels. Solute kinetics measurements showed higher myoglobin clearance during SDHDF (45.95±11.0 mL/min) compared to SDHD1 (20.11±5.2 mL/min, p<0.01) or to SDHD2 (21.39±3.55 mL/min, p<0.01). Likewise, there was a slight increase in β2-microglobulin removal in SDHDF (64.92±10.4 mL/min) compared to SDHD1 (59.78±17.0 mL/min, p<0.01) or to SDHD1 (53.01±7.71 mL/min, p<0.01), whereas there were no significant differences in urea and creatinine clearances. On the other hand, predialysis osteometabolic (serum PTH, calcium, phosphate, alkaline phosphatase, sodium, potassium, glucose and glycated hemoglobin), inflammatory (serum c-reactive protein and interleukin-6) or nutritional (serum albumin, total protein and lipid profile) parameters did not change significantly during the study. Left ventricular mass index, left atrial volume index and global longitudinal strain, assessed by echocardiography at the end of all 3 periods, were similar, as well as brain natriuretic peptide and homocysteine serum levels. Additionally, there were no significant changes in any quality of life features evaluated by Kidney Disease Quality of Life-Short Form, or symptoms assessed by Edmonton Symptom Assessment System Revised Renal, throughout the full course of the study. Conclusion In spite of mild increase of predialysis mean arterial pressure and hemoglobin levels along with greater removal of middle molecular weight solutes, no others clinical, laboratory, echocardiographic or quality of life findings differed significantly during the three periods. Together, these data do not provide evidence of clinically meaningful benefit from on-line hemodiafiltration over high-flux hemodialysis, both performed six times a week.

Hemodialysis raises oxidative stress through carbon-centered radicals despite improved biocompatibility.

Leukocyte activation and the resulting oxidative stress induced by bioincompatible materials during hemodialysis impact the prognosis of patients. Despite multiple advances in hemodialysis dialyzers, the prognosis of hemodialysis patients with complications deeply related to oxidative stress, such as diabetes mellitus, remains poor. Thus, we re-evaluated the effects of hemodialysis on multiple reactive oxygen species using electron spin resonance-based methods for further improvement of biocompatibility in hemodialysis. We enrolled 31 patients in a stable condition undergoing hemodialysis using high-flux polysulfone dialyzers. The effects of hemodialysis on reactive oxygen species were evaluated by two methods: MULTIS, which evaluates serum scavenging activities against multiple hydrophilic reactive oxygen species, and i-STrap, which detects lipophilic carbon-center radicals. Similar to previous studies, we found that serum hydroxyl radical scavenging activity significantly improved after hemodialysis. Unlike previous studies, we discovered that scavenging activity against alkoxyl radical was significantly reduced after hemodialysis. Moreover, patients with diabetes mellitus showed a decrease in serum scavenging activity against alkyl peroxyl radicals and an increase in lipophilic carbon-center radicals after hemodialysis. These results suggest that despite extensive improvements in dialyzer membranes, the forms of reactive oxygen species that can be eliminated during dialysis are limited, and multiple reactive oxygen species still remain at increased levels during hemodialysis.

Hemocompatibility of Polysulfone Hemodialyzers - Exploratory Studies on Impact of Treatment Modality and Dialyzer Characteristics.

The hemocompatibility of dialyzers for extracorporeal kidney replacement therapy (KRT) is of importance to minimize harmful reactions between blood constituents and the membrane. We investigated in these exploratory studies the hemocompatibility profile of several types of polysulfone dialyzers. Hemocompatibility of various high-flux polysulfone dialyzers were compared in two consecutive, prospective, randomized, crossover studies, each including 24 adult patients being at least 3 months on hemodialysis (HD) or on-line hemodiafiltration (HDF). These dialyzers, differing in membrane type, fiber geometry, sterilization method, and production technology, were each applied for 1 week in HD or HDF. Hemocompatibility was assessed through markers of complement activation, cell activation, coagulation, contact activation, and immunologic reactions. The patients in the two studies were on average 67±11 and 68±11 years old, 75% and 67% were male, and were on KRT for 5.4±5.0 and 4.4±3.6 years. The complement factors C3a and C5a increased early and transiently during treatment, less so with HDF than with HD, and with dialyzers combining wider inner fiber diameter (210 versus 185 µm) and advanced membrane type (Helixone plus versus Helixone). sC5b-9 increased in all study phases, reaching its highest level after 60 minutes, with lower values over the entire treatment (area under the curve) for HDF than HD, and for wider inner fiber diameter and advanced membrane type. Leukocytes decreased in the first 10 minutes, without significant differences between dialyzers. PMN elastase increased in the first hour, more so with HD than HDF. Thrombocytes decreased slightly in the first 30 minutes, with differences only between HDF and HD mode. IL-8 decreased from pre- to postdialysis, particularly on HDF. No differences were observed for kallikrein, IgE, and hsCRP. In these explorative studies we found indications to a comparable hemocompatibility profile of the investigated dialyzers. We observed distinctions in compounds between HDF and HD and for some dialyzer and membrane characteristics.

Randomized Controlled Open-Label Trial of Vitamin E-Bonded Polysulfone Dialyzer and Erythropoiesis-Stimulating Agent Response

A 1-year multicenter prospective randomized controlled study was conducted on the effects of vitamin E-bonded polysulfone dialyzers on erythropoiesis-stimulating agent response in hemodialysis patients. Major inclusion criteria were use of high-flux polysulfone dialyzers with 50-70 ml/min β2-microglobulin clearance over 3 months, transferrin saturation over 20%, same erythropoiesis-stimulating agent for over 3 months, and hemoglobin at 10-12 g/dl. Hemodialysis patients were placed in four interventional groups: two hemoglobin ranges (10.0-10.9 or 11.0-11.9 g/dl) and two dialyzers. Patients were randomly assigned by central registration to a vitamin E-bonded polysulfone dialyzers or polysulfone control group. Primary end point was relative erythropoiesis resistance index at baseline between groups at 12 months. Erythropoiesis resistance index was defined as total weekly erythropoiesis-stimulating agent dose divided by hemoglobin. There were no statistically significant differences in age or sex. There was no significant difference in relative erythropoiesis resistance index between vitamin E-bonded polysulfone dialyzers and control groups at 12 months (vitamin E-bonded polysulfone dialyzers: 1.1, control: 1.3). The vitamin E-bonded polysulfone dialyzers group showed better relative erythropoiesis resistance index than the control group at 11.0-11.9 g/dl hemoglobin (vitamin E-bonded polysulfone dialyzers: 1.0, control: 1.4 at 12 months, significant difference) but no difference at 10.0-10.9 g/dl hemoglobin. The overall relative erythropoiesis resistance index showed no difference between the vitamin E-bonded polysulfone dialyzers and control groups, although the change in relative erythropoiesis resistance index differed according to hemoglobin level.

Passive and Facilitated Transport of Cyanocobalamin (Vitamin B12) across Polymeric Membranes in Artificial Kidneys

Clearance of molecules by closed-circuit low-volume dialysis systems is limited by the accumulation of compounds in the dialysate and loss of the diffusion gradient. We sought to maintain dialysance of selected solutes by inducing “sink conditions” through the use of antibody-specific binding in the receiver compartment. Vitamin B12 was used as the test molecule since it is of clinically relevant size (molecular weight 1355 Da) and its clearance has been well-characterized for many dialyzer membranes. Using an in vitro haemodialysis model we perfused high-flux polymethylmethacrylate and low-flux polysulfone dialyzer membranes with known amounts of vitamin B12 through the intracapillary space. Clearances over time were calculated until equilibrium was reached within the fixed dialysate volume after 60 minutes. Anti-B12 monoclonal antibodies were then added to the receiver compartment reservoir. Under these sink conditions B12 clearance was restored, amounting to 77% and 118% of the integrated pre-equilibrium clearance for the high- and low-flux haemofilters, respectively. The magnitude of enhancement was such that the antibodies increased vitamin B12 clearance in low-flux dialyzers to levels observed in the high-flux devices. These studies demonstrate the feasibility of antibody-based sink conditions so as to promote substantial and highly selective solute clearance into small volume recirculating extracorporeal circuits.

145 A New High Flux Polysulfone Dialyzer with Waved Fibers Possessing Larger Pores Packed in Lower Fiber Density (Aps-Ea) Is Superior in Eliminating Low Molecular-Weight Proteins as Well as Small Toxins in Comparison to a Conventional Polysulfone Dialyzer with Straight Fibers Possessing Conventional Pores in Popular Fiber Density (Aps-El)

A NEW HIGH FLUX POLYSULFONE DIALYZER WITH WAVED FIBERS POSESSING LARGER PORES PACKED IN LOWER FIBER DENSITY (APS-EA) IS SUPERIOR IN ELIMINATING LOW MOLECULAR-WEIGHT PROTEINS AS WELL AS SMALL TOXINS IN COMPARISON TO A CONVENTIONAL POLYSULFONE DIALYZER WITH STRAIGHT FIBERS POSSESING CONVENTIONAL PORES IN POPULAR FIBER DENSITY (APS-EL) Emi Kihara, Miho Kando, Daisuke Okita, Nozomi Okada, Ken-ichi Taira, Yasuo Nomura, Kimiko Takahashi, Kazuko Arita, Katsutoshi Maeda, Hiroaki Oda, Oda Medical Clinic, Hiroshima, Japan. Advanced progress of a high flux polysulfone dialyzer has improved the prognosis of long-term hemodialysis (HD) patients in Japan. The purpose of this study is to elucidate beneficial effects of APS-EA compared to APS-EL in eliminating uremic toxins taking account of the differences in the shape of fibers (waved vs. straight), shape of baffles (extended vs. partial), average pore diameters (8.5 nm vs. 8.3 nm) and hallow fiber packed densities (58% vs. 71%). Elimination rates of low molecular-weight proteins (β2 microglobulin; β2-m and α1 microglobulin; α1-m) as well as small toxins (BUN, creatinine, uric acid) were estimated in 49 maintenance HD patients using APS-EL followed by APS-EA. Paired Student’s t-test was applied to the statistical analysis and p<0.05 was considered significant. Elimination rates are shown in the following table (mean±SD). β2-m α1-m BUN creatinine uric acid APS-EL 66.3±6.6 14.4±4.2 65.2±7.5 59.3±6.8 67.7±7.1 APS-EA 69.1±6.3 25.5±5.0 67.1±7.8 60.4±7.1 69.1±7.7 p value <0.01 <0.01 <0.01 <0.01 <0.01 APS-EA showed significantly higher elimination rates of low molecular-weight proteins and small toxins than APS-EL. An average value of Kt/V in APS-EA (1.35±0.30) was significantly higher than that in APS-EL (1.28±0.27), while serum albumin concentration in APS-EA (3.75 g/dl) showed slight decrease compared with that in APS-EL (3.87 g/dl). In conclusion, APS-EA, waved fibers with larger pores in less fiber packed density in an extended baffle, further developed the better performance of high flux polysulfone membrane.

On‐line hemodiafiltration reduces serum gentamicin levels much more efficiently than conventional hemodialysis

Although gentamicin pharmacokinetics during conventional hemodialysis (C-HD) have been investigated,1, 2 there is no information regarding gentamicin removal during on-line hemodiafiltration (OL-HDF). Here we present the results of a study that was undertaken to clarify this issue, after receiving the approval of the hospital scientific and ethic committees and the consent of patients. In 8 stable chronic hemodialysis patients undergoing OL-HDF (group A), and 6 other patients undergoing C-HD (group B), a single dose of 2 mg/kg gentamicin was administered intravenously over a period of 10 min. None of the patients had received gentamicin during the previous month, none had significant residual renal function, and all had well-functioning vascular accesses. Patient demographics are shown in Table I. Blood samples for gentamicin serum level measurements were drawn before its administration (time 0 = T0), 1 1/2 hr later, immediately before the start of the dialysis session (time 1 = T1), and 3 min after the end of the session (time 2 = T2). Serum was stored at −4°C until measurement. Gentamicin serum levels were measured on an AxSYM-FPIA analyzer (Abbott, Abbott Park, Ill). The dialysis session length was 240 min in all patients. The dialyzer blood flow rate was maintained between 330 and 350 mL/min, while the dialysate flow rate was kept at 700 mL/min in all patients. ON-HDF was performed using high-flux polyester-polymer-alloy (PEPA) dialyzers (FDX18GW, surface area 1.8 m2, Nikkiso, Tokyo, Japan) with a total of 18 L replacement fluid administered post-filter, while C-HD was performed using low-flux polysulfone dialyzers (Fresenius-F8, surface area 1.8 m2, Fresenius Medical Care, Bad Homburg, Germany). BUN and creatinine levels were also measured using conventional biochemical methods at times T1 and T2. Table II shows the results of the study. None of the parameters measured differed significantly between groups A and B, with the exception of gentamicin serum levels at the end of the study sessions. These end-dialysis gentamicin levels were significantly lower in group A patients compared with group B patients (1.2 ± 0.3 ng/ml vs. 2.3 ± 0.5 ng/mL, respectively; p < .001). No correlation was found between BUN or creatinine serum levels changes and the corresponding gentamicin changes during the study sessions. Although our investigation is not a detailed pharmacokinetic study, it clearly indicates that gentamicin is removed much more efficiently during ON-HDF compared with C-HD. This is an expected outcome since ON-HDF is performed with high-flux dialyzers, and the method used (diffusion plus convection) is more efficient than C-HD (diffusion only) in removing middle-sized molecular substances such as aminoglycosides (MW approximately 500 Da).3 It has been reported that high-flux polysulfone dialyzers permit better removal of gentamicin.4 However, it is not clear from our study whether the dialyzer, the method, or both are responsible for this difference. Although blood level monitoring is the gold standard method to adjust gentamicin dose in patients with end-stage renal disease undergoing dialysis, the difference between ON-HDF and C-HD should be kept in mind, especially when gentamicin is administered before dialysis, as has been proposed recently.5 More studies are needed to clarify the cause of lower gentamicin serum levels at the end of ON-HDF compared with C-HD, and to determine practical guidelines for gentamicin administration in patients undergoing OL-HDF.

The anticoagulant activity of enoxaparin sodium during on‐line hemodiafiltration and conventional hemodialysis

To study and compare the anticoagulant activity of enoxaparin sodium during on-line hemodiafiltration (OL-HDF) and conventional hemodialysis (C-HD). Enoxaparin was administered as an anticoagulant to 21 hemodialysis patients at the beginning of a single 4-hour OL-HDF session as an intravenous bolus dose of 80 IU/kg [DOSAGE ERROR CORRECTED] On-line hemodiafiltration was performed using a high-flux polyester polymer alloy dialyzer and a total of 18 L replacement fluid (session A). One week later, the study was repeated in the same patients during a single 4-hour session of C-HD using a low-flux polysulfone dialyzer (session B). Blood samples for the measurement of Hb, blood urea and nitrogen (BUN), activated partial thromboplastin time (APTT), and anti-Xa levels were taken before each study session and 5-minute postdialysis. In 13 more patients, the same study was performed during OL-HDF using a high-flux polysulfone dialyzer (session C). No differences were found between sessions A, B, and C when predialysis values for Hb, BUN, APTT, and anti-Xa were compared. The mean postdialysis APTT and anti-Xa values were 32.5+/-3.8 seconds and 0.19+/-0.11 IU/mL, respectively, in session A, 39.0+/-5.0 seconds and 0.71+/-0.17 IU/mL in session B, and 33.8+/-3.1 seconds and 0.35+/-17 IU/mL in session C (A vs. B, P<0.0001, for both parameters, A vs. C, P<0.003 for anti-XA, and B vs. C, P<0.005, for both parameters). The anticoagulant activity of enoxaparin sodium is decreased significantly during a 4-hour OL-HDF session compared with to a similar session of C-HD. The degree of the reduction seems to depend on the dialyzer's membrane.

An In Vivo‐In Vitro Study of Cefepime and Cefazolin Dialytic Clearance During High‐Flux Hemodialysis

To assess the influence of in vitro and in vivo hemodialysis with a new high-flux dialyzer on the clearance of cefazolin and cefepime; to assess the correlation of in vivo dialytic clearance of these antibiotics with blood flow rate; and to assess the correlation between in vitro and in vivo dialytic clearances of these antibiotics. Prospective, open-label, dialysis clearance study. A tertiary-care, university health science center. Five adults who received high-flux hemodialysis 3 times/week. Intervention. For the in vivo experiment, patients received a single intravenous infusion of cefazolin 1 g and cefepime 1 g before dialysis and then underwent a modified hemodialysis session. For the in vitro experiment, a buffered simulated plasma water (SPW) solution containing cefazolin and cefepime was used. Hemodialysis for both experiments was performed with use of a new high-flux polysulfone dialyzer. Cefazolin and cefepime dialytic clearances were determined at blood and/or SPW flow rates of 100, 200, 300, and 400 ml/minute after a 15-minute equilibration period. The degree of correlation of in vitro and in vivo clearances with blood flow rate was determined. Cefepime dialytic clearance increased proportionally with blood flow rate (p<0.01), reaching a maximum mean +/- SD value of 178.9 +/- 24.3 ml/minute at a blood flow rate of 400 ml/minute. Cefazolin dialytic clearance ranged from a mean +/- SD of 42.3 +/- 7.7 to 52.7 +/- 16 ml/minute; no significant correlation was noted between blood flow rate and dialytic clearance. In vitro cefazolin and cefepime dialytic clearances increased proportionally with SPW flow rate (p<0.05). After adjusting the in vitro cefazolin and cefepime dialytic clearances based on their degrees of protein binding, the correlation between the in vitro and in vivo cefepime dialytic clearances was significant (r(2)=0.91, p=0.04), but no significant correlation was noted between the in vitro and in vivo cefazolin clearances (r(2)=0.61, p=0.22). The in vivo hemodialysis clearances of cefepime and cefazolin with the new high-flux polysulfone dialyzer used in this study are markedly higher than values reported with conventional dialyzers but similar to values observed with other high-flux hemodialyzers. The in vivo dialytic clearance of cefazolin was significantly lower than the in vitro values, most likely due to cefazolin's high degree of protein binding. These results highlight the limitation of directly applying in vitro data to clinical situations.

The Impact of Standard High-Flux Polysulfone Versus Novel High-Flux Polysulfone Dialysis Membranes on Inflammatory Markers: A Randomized, Single-Blinded, Controlled Clinical Trial

This study is a prospective, randomized, single-blind, clinical trial over 12 months involving 60 stable hemodialysis patients comparing standard high-flux polysulfone dialyzer membranes with a novel high-flux polysulfone dialyzer membrane (Helixone; Fresenius Medical Care, St Wendel, Germany) modified in the fiber-spinning process to enhance middle-molecule clearance through changing the distribution of pore size and increased filtration. Markers of protein and lipid oxidation and inflammatory markers, including proinflammatory cytokines and cell adhesion molecules, were compared. The hypothesis tested was that improved clearances of middle molecules with the FX80 membrane would lead to less oxidative stress and inflammation compared with the high-flux polysulfone (HF80) membrane. Type of dialysis membrane used did not significantly affect lipid and protein peroxidation, C-reactive protein level, interleukin 6 level, or sgp130 level during 12 months. beta(2)-Microglobulin concentrations decreased significantly in the Helixone membrane group compared with those dialyzed using conventional polysulfone membranes during the study (-15%; 95% confidence interval, -20 to -10). Long-term dialysis with a Helixone membrane did not modify any parameters of oxidative stress or inflammation in this stable hemodialysis population compared with a high-flux polysulfone dialysis membrane.

Vasopressin administration facilitates fluid removal during hemodialysis

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Treatment of hirudin overdosage in a dialysis patient with heparin-induced thrombocytopenia with mixed hemodialysis and hemofiltration treatment

We report a patient who developed type II heparin-induced thrombocytopenia (HIT) and accidentally received a recombinant hirudin (r-hirudin) overdosage. Treatment with hemodialysis (HD) using high-flux polysulfone dialyzer and hemofiltration was performed. Length of treatment was adjusted, monitoring activated partial thromboplastin time (aPTT) to 1.5-2.5 times the mean of the normal range. She developed deep venous thrombosis and occlusion of vascular access. Only after cessation of heparin lock catheter, platelet count began to increase. After one year of treatment with acenocoumarol and additional low-dose r-hirudin, neither bleeding nor thrombotic episodes have been reported.

Does an alteration of dialyzer design and geometry affect biocompatibility parameters?

The aim of the study was to assess the biocompatibility profile of a newly developed high-flux polysulfone dialyzer type (FX-class dialyzer). The new class of dialyzers incorporates a number of novel design features (including a new membrane) that have been developed specifically in order to enhance the removal of small- and middle-size molecules. The new FX dialyzer series was compared with the classical routinely used high-flux polysulfone F series of dialyzers. In an open prospective, randomized, crossover clinical study, concentrations of the C5a complement component, and leukocyte count in blood and various thrombogenicity parameters were evaluated before, and at 15 and 60 min of hemodialysis at both dialyzer inlet and outlet in 9 long-term hemodialysis patients using the FX60S dialyzers and, after crossover, the classical F60S, while in another 9 patients, the evaluation was made with the dialyzers used in reverse order. The comparison of dialyzers based on evaluation of the group including all procedures with the FX60S and the group including procedures with the F60S did not reveal significant differences in platelet count, activated partial thromboplastin times, plasma heparin levels, platelet factor-4, D-dimer, C5a, and leukocyte count at any point of the collecting period. Both dialyzer types showed a significant increase in the plasma levels of the thrombin-antithrombin III complexes; however, the measured levels were only slightly elevated compared with the upper end of the normal range. Biocompatibility parameters reflecting the behavior of platelets, fibrinolysis, complement activation, and leukopenia do not differ during dialysis with either the FX60S or the F60S despite their large differences in design and geometry features. Although coagulation activation, as evaluated by one of the parameters used, was slightly higher with the FX60S, it was still within the range seen with other highly biocompatible dialyzers and therefore is not indicative of any appreciable activation of the coagulation system. Thus, the incorporation of various performance-enhancing design features into the new FX class of dialyzers does not result in a deterioration of their biocompatibility profile, which is comparable to that of the classical F series of dialyzers.

Dialyzer reuse and clinical outcomes—A 3‐year comparison between high flux polysulfone and polyflux® dialyzers

Purpose: This study evaluated improvements in dialyzer reuse parameters and clinical outcomes associated with a CQI project in a hospital‐based dialysis center in which high flux polysulfone dialyzers were replaced with high flux Polyflux® dialyzers (GAMBRO® Renal Products). Methods: Dialyzers were reprocessed using a Renatron® II Dialyzer Reprocessing System in conjunction with Renalin® sterilant (Minntech Corp.). Renalog® RM software was used to track dialyzer reprocessing rates and failures. Reasons for dialyzer failure included inadequate dialyzer volume; excess pressure; appearance; clotting during use; and maximum number of uses reached. The average number of dialyzer reuses with polysulfone dialyzers between January and June 2002 were compared to that achieved with Polyflux® dialyzers for the same periods in 2003 and 2004. Analysis periods were separated to avoid the impact of dialyzer transition on clinical parameters. Achievement of URR goals during these same periods was likewise compared. Results: Transition from polysulfone to Polyflux® dialyzers was associated with a &gt;40% increase in average number of reuses between 2002 and 2003 and a &gt;63% increase comparing the 2002 and 2004 periods. During the 2002 analysis period with polysulfone dialyzers the target URR of 65% was achieved in approximately 75% of hemodialysis patients; this increased to nearly 95% with Polyflux® dialyzers in both the 2003 and 2004 periods, despite more reprocessing of these dialyzers. Conclusions: These results demonstrate an improvement in both reuse efficiency and clinical outcomes associated with Polyflux dialyzers. Identifying clinical products through CQI studies that provide an economic and clinical advantage plays an important role in the success of hospital‐based hemodialysis.

Hemodialysis Procedure Does Not Affect the Levels of sICAM-1 and sVCAM-1 in Patients with End Stage Renal Disease

Atherosclerosis is by far the leading cause of mortality and morbidity in patients with end stage renal disease undergoing chronic hemodialysis (HD). Vascular endothelial cell adhesion molecules like the intercellular adhesion molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) are involved in the pathogenesis of atherosclerosis. Their soluble forms (sICAM-1, sVCAM-1) are considered potential serum markers of endothelial activation and atherosclerosis. The aim of this study was to clarify the influence of the HD procedure on the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease. We evaluated 35 clinically stable patients (18 males, 17 females, mean age 61 ± 12) on chronic HD treatment. Diabetes mellitus coexisted in eight patients and arterial hypertension in 23 patients. Blood was drawn before, every hour during, and after a single HD session in each patient. Low-flux cuprophane dialyzers (GFS 12®, Gambro, Lund, Sweden) were used in 22 and high-flux polysulfone dialyzers (Hemoflow F 60S®, Fresenius, Oberursel, Germany) in 13 cases. At 30 min into the HD session (n = 31, 20 low-flux HD, 11 high-flux HD) blood was drawn simultaneously from the entrance and the exit line of the dialyzer. From all these samples, serum concentrations of sICAM-1 and sVCAM-1 were determined by commercially available enzyme immunoassays (ELISA, R&D Systems, Minneapolis, USA). Results were corrected according to hemoconcentration, where appropriate. Plasma levels of sVCAM-1 were elevated in patients with end stage renal disease before the beginning of the dialysis session when compared to healthy controls (1449 ± 497 ng/mL vs. 691 ± 118 ng/mL). On the contrary, such an elevation was not found in the case of sICAM-1 (231 ± 58.5 ng/mL vs. 236.4 ± 96.8 ng/mL in healthy controls). These levels remained stable in all measurements throughout the dialysis procedure. Furthermore, serum sICAM-1 and sVCAM-1 levels remained unaltered after the passage of the dialyzer. The levels of sICAM-1 and sVCAM-1 were not influenced by the existence of diabetes mellitus, hypertension, or by the utilization of biocompatible, high flux dialyzers. Our study confirms that in chronic HD patients serum levels for sVCAM-1 are elevated. The levels of adhesion molecules are not affected by the HD procedure. These findings probably can be attributed to a decreased renal clearance or catabolism of sICAM-1 and sVCAM-1 and to the different sources of the two molecules. Neither coexisting diabetes mellitus nor arterial hypertension influences the circulating levels of these adhesion molecules. The functional role of sVCAM-1 and sICAM-1, the exact renal contribution to their metabolism, and their role as markers of atherosclerosis in chronic renal disease need further evaluation.

On-line clearance: a useful tool for monitoring the effectiveness of the reuse procedure.

Reprocessing of a dialyzer for repeated use in the same patient is widely practiced. The dialyzer fiber bundle volume (FBV) is monitored as an indicator of the dialyzer's suitability for continued use, with standards for reprocessed dialyzers requiring a FBV of greater than 80% of a new dialyzer to be maintained. We have used on-line measurement of clearance of sodium (OLC module, Fresenius Medical Care, Walnut Creek, CA) to assess small molecule clearance changes during and between treatments for a group of 29 chronic hemodialysis patients who reused high flux polysulfone dialyzers (F80, Fresenius Medical Care, Lexington, MA) reprocessed using citric acid and heat (95 degrees C). Data pertaining to the initial, 5th, 10th, and 15th uses were analyzed and showed that, within a single dialysis session, there was a trend for the clearance to reduce throughout the treatment (p < 0.001). Overall, there was also a trend for clearances to decline with increasing number of reuses (p < 0.008). Changes in FBV occurred, but such changes remained within the guidelines suggested by standards. It is concluded that on-line clearance measurements provide a simple noninvasive method to monitor dialyzer performance over each use and between uses.

Does Monitoring of Pre-/Post-Dialyzer Pressure Difference Improve Efficiency in Intermittent Hemodialysis?

Background: Continuous monitoring of pre-/post-dialyzer pressure difference (ΔP) is widely used in continuous renal replacement therapies to monitor extracorporeal circuit function. The aim of this study was to verify whether ΔP may help to identify chronic subclinical worsening of dialysis quality due to incomplete dialyzer clotting in intermittent hemodialysis. Methods: Nine chronic hemodialysis patients were enrolled in the study and dialyzed twice (high-flux polysulfone dialyzer) with ΔP and urea-clearance monitoring: the first session with a standard anticoagulation and the second without. To verify whether a visible clotting of the dialyzer precedes or follows a significant ΔP increase, we checked the dialyzers for the presence of red clots after a saline flush performed when a 50% increase in ΔP was registered. Results: In the second dialysis session after a 50% increase in ΔP (documented in 7/9 patients), all dialyzers, after saline flush, showed a visible fiber clotting but not a significant reduction (>15%) in urea clearance. In the majority of the patients (6/7), until a few minutes before complete occlusion of the extracorporeal circuit, the urea clearance did not change significantly (–8.9 ± 12.7%). Conclusions: The usual check of the presence or absence of red clots in the dialyzer at the end of the dialysis session is enough, in the absence of red clots, to ensure that dialyzer efficiency is maintained during the whole treatment. Contrary to what is applied in CRRT, a continuous monitoring of ΔP during intermittent hemodialysis would not significantly help to unmask unnoticed inefficient hemodialysis sessions.

Impact of Hemodialysis Membrane and Permeability on Neutrophil Transmigration in vitro

Background/Aim: The impact of dialysis membrane permeability on neutrophil transmigration properties in vitro was examined in the present study. This issue has not been fully scrutinized before. Methods: We studied the capacity of neutrophils collected from a group of dialysis patients randomly treated with cuprophan, low- or high-flux polysulfone, to transmigrate in vitro through a membrane covered with fibronectin (a main constituent of the endothelial basement membrane). The hemodialysis-induced quantitative changes in expression of adhesion molecules were examined in parallel. Results: At the end of dialysis, neutrophils collected from patients treated with high-flux polysulfone dialyzers had a significantly higher transmigration index than neutrophils from patients treated with low-flux polysulfone membrane (p < 0.01) or cuprophan membrane (p < 0.01), and approached the level of transmigration observed in neutrophils collected from healthy controls. In the groups treated with low-flux polysulfone and cuprophan dialyzers, the transmigration capacity was significantly lower (p < 0.02) compared to neutrophils from healthy subjects. We also noted that differences between low- and high-flux polysulfone dialysis, in the context of transmigration properties, were not mirrored by changes in adhesion phenotype, which strengthens the view that there is no strict relationship between these two features. Conclusion: The study demonstrates that high-flux polysulfone dialysis, as opposed to low-flux polysulfone and cuprophan treatment, improves the transmigration properties of circulating neutrophils, despite similar effects on adhesion molecule phenotypes. A plausible mechanism is that potentially toxic middle range molecules that inhibit neutrophil migration are more efficiently eliminated during high-flux polysulfone dialysis, but this explanation requires further support.

High-flux dialysis lowers plasma leptin concentration in chronic dialysis patients.

Leptin is a protein produced by fat cells and involved in body weight regulation. Plasma leptin is significantly higher in some hemodialysis (HD) patients than in normal controls. We examined the influence of dialyzer membrane biocompatibility and flux on elevated plasma leptin concentrations in hemodialysis patients. Employing a crossover design, leptin and tumor necrosis factor-alpha (TNF-alpha) levels were serially determined in eight chronic dialysis patients. Patients were dialyzed sequentially on low-flux cellulosic (TAF) dialyzers, low-flux (F8) polysulfone, high-flux (F80B) polysulfone, then low-flux polysulfone and cellulosic dialyzers again. Mean leptin concentrations were similar when low-flux polysulfone or cellulosic dialyzers were employed (141.9+/-24.2 microg/L versus 137.8+/-18.4 microg/L, respectively (P=NS). In contrast, leptin fell significantly on the high-flux polysulfone dialyzer (99.4+/-16.2 microg/L) compared with cellulosic (P < 0.005), and low-flux polysulfone dialyzers (P < 0.02). Leptin clearance by the high-flux polysulfone dialyzer was significantly higher than the low-flux dialyzers (50.4+/-21.5 v -9.6+/-10.3 mL/min; P=0.043), but did not account fully for the 30% decline in plasma leptin during the high-flux arm of the study. Concentrations of TNF-alpha were lower when high-flux polysulfone dialyzers were employed, but there was no correlation of individual TNF-alpha levels with leptin concentrations. High-flux dialysis lowers plasma leptin concentrations an average of 30%, but biocompatibility does not influence leptin levels. The decrease in plasma leptin on high-flux dialysis cannot be explained solely by enhanced clearance.

Pharmacokinetics of Recombinant Hirudin in Hemodialyzed End-stage Renal Failure Patients

Recently, hirudin was used for the first time as an anticoagulant during hemodialysis in men. Pharmacokinetic data of this compound in end-stage renal failure are however not available. In this study, the pharmacokinetics of recombinant hirudin (HBW 023) was evaluated in hemodialysis-treated end-stage renal failure patients. HBW 023 was administered as a bolus at the start of a single dialysis (0.02 to 0.08 mg/kg) in 20 patients, and plasma hirudin levels were followed during this and the 5 following dialyses, without additional hirudin administration. The initial dialysis (HD1) was performed with a low flux polysulfone dialyzer, the following dialyses (up to HD6) with a high flux polysulfone dialyzer and regular heparin. Hirudin levels averaged 504.0 +/- 214.0 and 527.7 +/- 217.1 ng/ml in the middle and at the end of HD1, and then gradually decreased to 15.2 +/- 15.2 ng/ml at the end of HD6. Pharmacokinetic data were compared to those obtained in healthy controls (n = 5), receiving the same dose, and reaching the same peak hirudin level. Hirudin half-life was > 30 times longer in hemodialysis patients (51.8 +/- 15.6 vs. 1.7 +/- 1.5 h, p < 0.001), whereas area under the curve was > 60 times higher (34,669 +/- 14,898 vs. 545 +/- 205 ng/ml x h, p < 0.001). Distribution volume was lower in hemodialysis patients (11.0 +/- 3.1 vs. 14.1 +/- 2.01, p < 0.05). Hirudin disappearance rate was the same during high flux polysulfone dialysis as during interdialytic periods. Hirudin removal was markedly higher in those patients still maintaining some residual renal function and parameters of hirudin removal were significantly correlated to residual creatinine clearance. It is concluded that hirudin removal from the body is markedly depressed in hemodialyzed end-stage renal failure patients and that even minor residual renal function may increase this removal rate.