High-flux Polysulfone Membrane Research Articles

The influence of vitamin E-coated dialysis membrane on oxidative stress during a single session of on-line hemodiafiltration

Background/Aim. Oxidative stress is an important risk factor for the development of cardiovascular atherosclerotic diseases in the population of patients treated with regular hemodialysis. Bioincompatibility of the dialysis membrane and increased concentration of endotoxin in the hemodialysis solution are two main factors that can trigger oxidative stress. This paper was intended to examine the effect of a vitamin E-coated membrane on oxidative stress during a single session of on-line hemodiafiltration. Methods. Twenty-four patients undergoing hemodiafiltration with vitamin E-coated polysulfone dialysis membrane (Leoceed 21H) were examined, followed by a polysulfone dialysis membrane treatment without vitamin E (FX800). The following parameters of oxidative stress were measured: superoxide anion radical (O2-), hydrogen peroxide (H2O2), thiobarbutyric acid reactive substances (TBARS), nitric oxide (NO2-), catalase (CAT), superoxide dizmutase (SOD), and reduced glutathione (GSH) activity. Statistical analysis included the Kolmogorov-Smirnov test, Student-t test and Wilcoxon test. Results. On-line hemodiafiltration using a high-flux polysulfone vitamin E-coated membrane led to significant reduction of TBARS concentration and SOD activity, while the on-line hemodiafiltration session using a high-flux polysulfone membrane that is not vitamin E-coated induced a significant increase in H2O2 concentration in the serum and a decrease in SOD activity. There was no statistical significance among the other parameters of oxidative stress. Conclusion. A single session of on-line hemodiafiltration using a vitamin E-coated polysulfone membrane significantly affects oxidative stress. After a single session of on-line hemodiafiltration using a vitamin E-coated membrane, the concentration of TBARS has significantly decreased. The decreased activity of superoxide dismutase could be a consequence of an increased loss of microelements during an on-line hemodiafiltration session using a high-flux polysulfone membrane. Patient selection, continuous on-line hemodiafiltration using a vitamin E-coated polysulfone membrane over a 3?6 month period and increased antioxidant protection capacity could possibly reduce the risk of cardiovascular morbidity and mortality in patients treated by hemodialysis.

Amino Acid Loss during Continuous Venovenous Hemofiltration in Critically Ill Patients

Background/Objectives: During continuous venovenous hemofiltration (CVVH), there is unwanted loss of amino acids (AA) in the ultrafiltrate (UF). Solutes may also be removed by adsorption to the filter membrane. The aim was to quantify the total loss of AA via the CVVH circuit using a high-flux polysulfone membrane and to differentiate between the loss by ultrafiltration and adsorption. Methods: Prospective observational study in ten critically ill patients, receiving predilution CVVH with a new filter, blood flow 180 mL/min, and predilution flow 2,400 mL/h. Arterial blood, postfilter blood, and UF samples were taken at baseline, and 1, 8, and 24-h after CVVH initiation, to determine AA concentrations and hematocrit. Mass transfer calculations were used to determine AA loss in the filter and by UF, and the difference between these 2. Results: The median AA loss in the filter was 10.4 g/day, the median AA loss by UF was 13.4 g/day, and the median difference was –2.9 g/day (IQR –5.9 to –1.4 g/day). For the individual AA, the difference ranged from –1 g/day to +0.4 g/day, suggesting that some AA were consumed or adsorbed and others were generated. AA losses did not significantly change over the 24-h study period. Conclusion: During CVVH with a modern polysulfone membrane, the estimated AA loss was 13.4 g/day, which corresponds to a loss of about 11.2 g of protein per day. Adsorption did not play a major role. However, individual AA behaved differently, suggesting complex interactions and processes at the filter membrane or peripheral AA production.

Short-Term Effects of Branched-Chain Amino Acids–Enriched Dialysis Fluid on Branched-Chain Amino Acids Plasma Level and Mass Balance: A Randomized Cross-Over Study

The hemodialysis (HD) session per se is a catabolic event contributing to protein-energy wasting via several mechanisms including nutrient losses. Amino acids (AAs) losses in the dialysate are estimated from 6 to 10g per treatment. The HD patient plasma AA concentration is usually lower than in normal subjects. This is even more marked in patients with long dialysis vintage or malnutrition. The aim of the study was to evaluate the effect on mass balance of a branched-chain AA (BCAA)-enriched (valine, isoleucine, leucine) dialysis fluid in a group of 6 stable HD anuric patients, fasting since 12hours. The specific choice of BCAA relied on their key role on protein and muscle anabolism and their usual decreased plasma concentration in HD patients. Each patient was prescribed in a cross-over design and random order, either receiving a standard high-flux HD or an HD treatment using a BCAA-enriched acid concentrate designed to achieve a physiological plasma concentration of BCAAs. HD prescription remained unchanged during the 2 phases of study. Dialysate electrolytes prescription was kept constant for each individual patient, as well as dialysate glucose concentration (5.5 mmol/L). Pre- and post-dialysis BCAAs concentrations were measured by Ion-Exchange Liquid Chromatography. Postdialysis concentrations were corrected for hemoconcentration, and net mass transfer was calculated. Six stable prevalent end-stage kidney disease patients were studied. They consisted of 5 men and 1 woman, aged 69.9years, with body mass index of 25.2kg/m2. Treatment schedule consisted of treatment time 4hours, high-flux polysulfone membrane (1.8m2), blood flow 350mL/minute, and dialysate/blood flow ratio at 1.5. The average BCAAs concentration in dialysate was targeted to physiological levels and assessed in 6 different samples, respectively for plasma valine, isoleucine, and leucine at 271, 78, and 145 μmol/L. With standard dialysate, plasma valine decreased from 204.5 to 130.8 (P=.0014). Plasma isoleucine and leucine changes were not significant, respectively from 65.7 to 59.3 μmol/L and 110.3 to 113.4 μmol/L. When using the BCAA-enriched dialysis fluid, plasma valine increased from 197.2 to 269.2 μmol/L (P=.0001), plasma isoleucine and leucine respectively from 63.2 to 84.7 (P=.0022) and from 107.2 to 161.6 μmoles/L (P=.0002). Dialysis dose estimated from KT/V did not differ between the sessions. The mass transfer with BCAA-enriched dialysate was +115, +16, and+83 μmol per session for leucine, isoleucine, and valine, respectively. In conclusion, the addition of BCAAs at physiological concentration in the dialysis fluid contributes to restore physiological plasma concentrations for valine, isoleucine, and leucine at the end of a dialysis session. As BCAAs are essential to muscle balance, this could help to limit losses of BCAAs, restore physiological BCAAs concentrations, and decrease muscle catabolism observed during the HD treatment. Further outcome-based studies are needed to confirm this hypothesis on a larger scale and longer treatment time.

Impact of dialyzer membrane flux on metal clearance in hemodialysis patients

Deficiency of essential trace elements (such as Cu or Zn) and accumulation of potentially toxic trace elements (as Cd or Pb) are both known to have adverse effects in hemodialysis (HD) patients. Up to our knowledge, no studies about the permeability of low and high flux polysulfone membranes on metal ions during hemodialysis are available. Therefore, the aim of the present study was to address this issue. Forty one hemodialysis patients (19 were using high flux polysulfone membrane while the remaining were using low flux one) participated in the study. Blood levels of Cu, Zn, Cd and Pb were determined by graphite furnace atomic absorption spectrometry among HD patients, before and after dialysis session, as well as among matched 40 healthy persons. Blood concentrations of Cu and Zn in the whole hemodialysis group was significantly lower than those of the healthy control group, on the other hand the toxic metals (Cd and Pb) levels were observed to be significantly higher among HD patients compared to the normal persons. Among the hemodialysis group, there were no significant differences between the low and high flux dialyzer groups in terms of pre-dialysis blood levels of Cu, Zn, Cd and Pb. In addition, significantly decreased levels of all metal ions were observed after dialysis sessions using either low or high flux membranes. An exception was Pb which did not show any difference between pre-dialysis and post-dialysis values in the low flux groupIn conclusion Zn and Cu deficiencies should be considered in the treatment of these patients. High flux membranes are more efficient than low flux ones in removing excess Cd and Pb. Therefore, when high flux membranes are used, chelation therapy might not be required for Cd and Pb overload.

Study of Effect of High-Flux Versus Low-Flux Dialysis Membranes on Parathyroid Hormone

<b> </b><b>Objective</b><b>:</b><b> </b>Investigate the influence of permeability of low-flux versus high-flux dialysis membranes on intact PTH during hemodialysis. <b>Background</b><b>:</b> Hyperparathyroidism is a common finding in patients with renal insufficiency and parathyroid hormone (PTH) is considered a uremic toxin responsible for many of the abnormalities of the uremic state and bone disease. <b>Materials and Methods</b><b>:</b> Forty adult patients on regular hemodialysis were enrolled in a prospective study. Low-flux polysulfone membranes were used for at least 6 months and then the patients were switched to use high-flux polysulfone membranes for 1 month. Serum electrolytes and intact PTH before and after dialysis were compared before and after changes in dialysis membrane. <b>Results</b><b>:</b> At the end of the 1-month use of high-flux filters, predialysis intact PTH level (415.96 ± 226.72 ng/dL) showed a significant decline (P < 0.05) compared to the predialysis intact PTH (312.28 ± 191.98 ng/dL) with low-flux membranes. Intact PTH level correlated negatively with serum calcium and positively with serum phosphorus levels only in the predialysis samples with the use of low-flux but not high-flux filters. <b>Conclusion</b><b>:</b> High-flux dialysis membranes are more efficient in removal of intact PTH, one of the middle-sized uremic toxins, than low-flux membranes.

Comparative study of the effect of high-flux versus low-flux dialysis membranes on metabolic abnormalities in chronic hemodialysis patients

Objective The aim of the study was to compare the effect of permeability of low-flux versus high-flux dialysis membranes on control of metabolic abnormalities in chronic hemodialysis patients. Background End-stage renal disease is associated with multiple physiological and metabolic disturbances, including hypertension, anemia, hyperparathyroidism, dyslipidemia, malnutrition, and other serious problems that markedly and negatively affect prognosis and the quality of life of uremic patients. New dialyzers have large pores and they are more compatible than pure cellulose membranes; thus, they provoke less inflammatory reaction and are more efficient in removal of uremic toxins. Materials and methods Forty adult patients on regular hemodialysis were enrolled in a prospective study. Low-flux polysulfone membranes were used for at least 6 months and then patients were switched to use high-flux polysulfone membranes for 1 month. Serum electrolytes and intact parathyroid hormone (PTH) before and after dialysis were compared before and after changes in dialysis membrane. Results At the end of the 1-month use of high-flux filters, a highly significant increase in the mean of hemoglobin levels from 9.50 ± 1.08 to 10.29 ± 1.04 (P = 0.001) was evident. Postdialysis mean arterial blood pressure decreased significantly after use of high-flux dialysis (P = 0.002). There were highly significant decreases in predialysis blood urea nitrogen, phosphorus, sodium, and potassium after the use of high-flux filters. Predialysis intact PTH level (415.96 ± 226.72 ng/dl) showed a significant decline (P < 0.05) compared with the predialysis intact PTH (312.28 ± 191.98 ng/dl) with low-flux membranes. Conclusion High-flux dialysis membranes are more efficient in control of metabolic abnormalities in chronic hemodialysis patients than low-flux membranes.

SymbolEffect of high-flux dialysis membrane on uremic pruritus and solute clearance of maintenance hemodialysis patients

AbstractBACKGROUND:How to effectively remove uremic toxins, reduce complications and improve the quality of life and long-term prognosis in maintenance hemodialysis patients has been a hot spot.OBJECTIVE:To compare the effects of high-flux and low-flux polysulfone membrane dialyzers on uremic prurit

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.

Pulmonary hypertension in hemodialysis patients without arteriovenous fistula: the effect of dialyzer composition

Pulmonary hypertension (PHT) increases mortality rate in hemodialysis (HD) patients. Numerous clinical, hemodynamic, and metabolic abnormalities have been suggested to be associated with the development of PHT in HD patients. We aimed to investigate the acute effects of two different dialyzer membranes on pulmonary arterial pressure (PAP) throughout a HD session in maintenance HD patients. Seventy-four HD patients dialyzed through permanent tunneled jugular central venous catheter were enrolled. A first-use cellulose acetate and high-flux polysulfone dialysis membrane were tested using a crossover design. For each membrane, pre- and post-dialysis pulmonary artery pressures were measured echocardiographically. Elevated pulmonary artery pressure was observed in 68.8% of patients (n = 51), whereas mild PHT was observed in 28.3% of patients (n = 21) and moderate PHT in 40.5% (n = 30). Decrease in pulmonary artery pressure following HD procedure performed using high-flux polysulfone membrane was significantly higher than the decrease observed following HD procedure performed using cellulose acetate membrane (p < 0.05). Significant decrease in pulmonary artery pressures was observed only after HD procedures performed using high-flux polysulfone membrane (p < 0.05). Ultrafiltered volume was only significantly correlated with the decrease in pulmonary artery pressure observed after HD procedure performed through high-flux polysulfone membrane (β = 0.411, p < 0.05). PHT seems to be prevalent among HD patients even in the absence of AV fistula and abnormal cardiac functions. Membrane composition seems to be important, which may overwhelm the improving effects of ultrafiltration.

Pharmacokinetics of Sulfobutylether-Beta-Cyclodextrin and Voriconazole in Patients with End-Stage Renal Failure during Treatment with Two Hemodialysis Systems and Hemodiafiltration

Sulfobutylether-beta-cyclodextrin (SBECD), a large cyclic oligosaccharide that is used to solubilize voriconazole (VRC) for intravenous administration, is eliminated mainly by renal excretion. The pharmacokinetics of SBECD and voriconazole in patients undergoing extracorporeal renal replacement therapies are not well defined. We performed a three-period randomized crossover study of 15 patients with end-stage renal failure during 6-hour treatment with Genius dialysis, standard hemodialysis, or hemodiafiltration using a high-flux polysulfone membrane. At the start of renal replacement therapy, the patients received a single 2-h infusion of voriconazole (4 mg per kg of body weight) solubilized with SBECD. SBECD, voriconazole, and voriconazole-N-oxide concentrations were quantified in plasma and dialysate samples by high-performance liquid chromatography (HPLC) and by HPLC coupled to tandem mass spectrometry (LC-MS-MS) and analyzed by noncompartmental methods. Nonparametric repeated-measures analysis of variance (ANOVA) was used to analyze differences between treatment phases. SBECD and voriconazole recoveries in dialysate samples were 67% and 10% of the administered doses. SBECD concentrations declined with a half-life ranging from 2.6 +/- 0.6 h (Genius dialysis) to 2.4 +/- 0.9 h (hemodialysis) and 2.0 +/- 0.6 h (hemodiafiltration) (P < 0.01 for Genius dialysis versus hemodiafiltration). Prediction of steady-state conditions indicated that even with daily hemodialysis, SBECD will still exceed SBECD exposure of patients with normal renal function by a factor of 6.2. SBECD was effectively eliminated during 6 h of renal replacement therapy by all methods, using high-flux polysulfone membranes, whereas elimination of voriconazole was quantitatively insignificant. The SBECD half-life during renal replacement therapy was nearly normalized, but the average SBECD exposure during repeated administration is expected to be still increased.

Ich Denk’ es War Ein Gutes Jahr (Reinhard Mey, 1968) – The year 2010 Balance

As Editors of the IJAO, we committed to consolidating its legacy and expanding its function of providing clinicians with updated information on available treatments based on artificial, bioartificial, and tissue engineered organs. A short analysis of this year’s contributions to the IJAO - without pretending to be exhaustive - provides interesting information on the evolution of the field. Many contributions focused on hemodialysis (HD) and filtration treatments of acute or chronic kidney failure patients, the actual legacy of the past. The analysis of these papers shows that current research mainly focuses on identifying factors that would improve the quality of life of HD patients. Guney et al (2) showed that socio-psychological factors, such as depression, the mental component score, age and unemployment, are the best predictors of poor sleep quality in HD patients. Materials used for the HD treatment and the administered drugs seem also to play a role. Matsumura et al (3) reported that HD with high flux polysulfone membranes at whose surface vitaminE was bonded could reduce intradialytic hypotension, presumably by reducing the intradialytic oxidative stress caused by dialyzer bioincompatibility. Davenport (4) reported that in HD treatments using a negative sodium gradient patients could be ultrafiltered without setting up intracompartmental fluid gradients. The poor reliability of current techniques to monitor sodium levels in dialysate and the patient limits this approach. Tao et al (5) reported that the use for one year of dialysate meeting the bacteriological purity requirements of some national agencies would almost double the serum level of lipoprotein (a) (Lp(a)), a risk factor for cardiovascular complications, whereas in patients treated with ultrapure dialysate Lp(a) levels did not increase significantly. Anemia in HD is generally treated with in

Effect of FX Dialysers on Systemic Inflammation and Quality of Life in Chronic Haemodialysis Patients

Background: The FX class of haemodialysers features a new class of high-flux polysulfone membrane which has been suggested to induce less inflammation. Methods: This was a randomized, cross-over study performed on 33 haemodialysis patients. Patients were randomized to FX60 or HF80 dialysers for 3 months and then changed to the other dialyser. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at baseline, and every 3 months. The Kidney Disease Quality of Life Short Form was also administered. Results: The mean of the difference in the IL-6 level between dialysers was 1.4 ± 8.0 pg/ml (95% CI –1.8, 4.5 pg/ml). There was no significant difference in TNF-α (95% CI –0.35, 0.18 pg/ml) or CRP levels (95% CI –2.67, 6.20 mg/l). The quality of social interaction and role limitations caused by physical health problems were significantly higher with the FX60, p = 0.04 and 0.047, respectively. Conclusions: The FX dialysers do not result in a significant difference in the level of systemic inflammation compared to the HF80.

Cell‐Free Plasma DNA during Peritoneal Dialysis and Hemodialysis and in Patients with Chronic Kidney Disease

The mechanisms of clearance of circulating plasma DNA are not fully understood, and so we aimed to examine it in patients with impaired renal function compared with healthy individuals. We also assessed the effect of peritoneal dialysis and hemodialysis on circulating plasma cell-free DNA (cfDNA) in our treated patients. Overall, 20 healthy volunteers, 20 patients with chronic kidney disease (CKD), 18 patients undergoing peritoneal dialysis (PD), and 17 patients on hemodialysis (HD; high-flux polysulfone membrane) were examined. Cell-free DNA levels were determined using real-time GADPH gene sequence amplification. The levels of cfDNA in all groups of our patients did not differ significantly from those of healthy volunteers. In HD patients, cfDNA levels were significantly increased compared with those of CKD patients (P < 0.05) and PD-treated patients (P < 0.01). In PD-treated patients, cfDNA was detectable in overnight effluent, with its levels correlating inversely with the duration of PD treatment (r=-0.619, Spearman's coefficient, P= 0.008). Factors contributing to these differences may include changes in the quality and quantity of the cell population of the peritoneum, highlighting the need for additional studies clarifying the dynamics of cfDNA during PD. The plasma levels of cfDNA do not seem to be dramatically altered even in CKD patients or those on PD or HD (as long as they are measured prior to the procedure in the latter two). Our data suggest renal elimination is not the main mechanism of circulating cfDNA clearance.

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.

Effect of Hemodiafiltration on Pregnancy-Associated Plasma Protein A (PAPP-A) and Related Parameters

Background. Dialysis patients are at high risk of vascular/cardiovascular complications with multifactorial pathogenesis, and pregnancy-associated plasma protein A (PAPP-A) is one of the new markers related to cardiovascular risk. Because hemodiafiltration (HDF) is supposed to be better for cardiovascular status, the aim of this study was to describe whether it has any advantage concerning changes of PAPP-A and related molecules during the session in comparison with hemodialysis (HD). Methods. The studied group consisted of 20 chronic hemodialysis patients. In each patient, PAPP-A and related parameters—IGFBP-4 (insulin like growth factor binding protein), IGF-I (insulin like growth factor), and two MMPs (matrix metalloproteinases)-2 and 9—were determined both during a single online HDF session (high-flux polysulfone membrane HF80, postdilution) and during a single HD session (low-flux polysulfone membrane F6, F7) at time 0 (start), 15 min, 120 min, and 240 min (end) of the session. Results. PAPP-A, elevated at baseline in dialysis patients, changes significantly both during HDF and HD without significant differences between these two procedures (mean levels during HDF were 24.3, 53.9, 24.3, and 27.3 mIU/L). It increases more than two-fold from 0 to 15 min of the session (p < 0.001) and then decreases until the end of the session (p < 0.001). MMP-2 decreased slightly during both sessions (p < 0.001), and changes of other molecules were only minimal. Conclusion. A single HDF session compared to HD has no advantage in the decrease of PAPP-A and other tested molecules, all of them related to cardiovascular risk. Studies aimed at a long-term effect of both procedures on these parameters would be needed to further evaluate these therapeutical strategies.

Lymphocyte Apoptosis: Role of Uremia and Permeability of Dialysis Membrane

Background: Uremia is associated to host defense mechanism disorders. Lymphocyte apoptosis, which may cause alteration of the immune system, is increased in uremic patients. The aim of the present study was to determine if, in addition to uremia, dialysis membranes with different biocompatibility and permeability have an effect on lymphocyte apoptosis. Methods: Cell apoptosis and Fas expression were assessed using flow cytometry in four groups of patients: (1) uremic non-dialyzed (Non-D) patients; (2) hemodialysis (HD) patients on hemophan; (3) low-flux polysulfone, and (4) high-flux polysulfone membrane. Ten healthy volunteers were used ascontrols. Results: At baseline, lymphocytes from patients on hemophan showed an increase in apoptosis (18.4 ± 6.9%) as compared with Non-D (7.2 ± 2.8%; p < 0.001), low-flux (6.4 ± 2.4%; p < 0.001), high-flux (2.6 ± 1.2%; p < 0.001) and controls (2.0 ± 1.0%; p < 0.001). Fas expression was similar in lymphocytes from Non-D and hemophan dialyzed patients (40.5 ± 5% vs. 40.4 ± 6%), and in both groups it was greater than low-flux (30%±7%; p < 0.001), high-flux (11 ± 4%; p < 0.001) and controls (12.6 ± 3%; p < 0.001). When lymphocytes were cultured for 48 h, apoptosis was similar in Non-D and hemophan (27.0 ± 4.3% vs. 27.1 ± 6.9%); apoptosis of lymphocyte from patients on low-flux (14.1 ± 3.5%) was greater than on high-flux polysulfone membrane (7.0 ± 2.0%; p < 0.001). Conclusion: These findings suggest that in dialysis patients lymphocyte apoptosis is influenced not only by the biocompatibility but also by the permeability of the dialysis membrane.

Ultrapure dialysate decreases plasma pentosidine, a marker of “carbonyl stress”

Background: Advanced glycation end products (AGEs) and their reactive carbonyl precursors accumulate in renal failure (“carbonyl stress”). Carbonyl stress derives from a broad derangement in the nonenzymatic biochemistry of both carbohydrates and lipids. We tested the influence of dialysate quality on plasma level of pentosidine, an AGE moiety taken as a surrogate marker of carbonyl stress, in hemodialysis patients. Methods: Plasma pentosidine is measured by means of high-performance liquid chromatography in patients hemodialyzed successively with a conventional and an ultrapure endotoxin-free dialysate. Results: Dialysate endotoxin level decreased from 0.040 ± 0.017 EU/mL before the switch to the new water supply system to less than the detection limit (<0.001 EU/mL) after the switch. Plasma pentosidine levels decreased from 1.55 ± 0.61 nmol/mL before the switch to 1.38 ± 0.52 nmol/mL (P < 0.0001) and 1.31 ± 0.50 nmol/mL (P < 0.0001) 3 and 6 months after the switch to an ultrapure dialysate, respectively. Decreases in plasma pentosidine levels were similar regardless of dialyzer membrane type; ie, high-flux polysulfone, high-flux polymethylmethacrylate, and low-flux cellulose acetate membranes. Unexpectedly, plasma triglyceride levels decreased from 150 ± 116 mg/dL (1.69 ± 1.31 mmol/L) before the switch to 124 ± 79 mg/dL (1.40 ± 0.89 mmol/L; P < 0.01) and 119 ± 75 mg/dL (1.34 ± 0.85 mmol/L; P < 0.01) 3 and 6 months after the switch despite unchanged total cholesterol levels, respectively. Changes in pentosidine levels were unrelated to those in triglycerides, and both were unrelated to C-reactive protein levels, which remained stable throughout the study. Conclusion: Ultrapure dialysate reduces plasma pentosidine levels and improves plasma triglyceride levels in hemodialysis patients through still undefined mechanisms.

Single-dose pharmacokinetics of ofloxacin during continuous venovenous hemofiltration in critical care patients

Background:Ofloxacin is a quinolone administered to patients with severe infections. Pharmacokinetic data on ofloxacin in critically ill patients on renal replacement therapy are sparse and conflicting. Methods:Eight patients with anuric acute renal failure were administered 400 mg of ofloxacin intravenously. The pharmacokinetics of ofloxacin was analyzed during continuous venovenous hemofiltration (CVVH) with a high-flux polysulfone membrane. Serum and ultrafiltrate levels of ofloxacin were measured by means of high-performance liquid chromatography. Results:Mean serum ofloxacin concentration peak was 5.5 ± 0.7 mg/L. Elimination half-life, hemofiltration clearance, and total removal were 2.8 ± 0.5 hours, 89.9 ± 4.5 mL/min, and 76.9% ± 7.1%, respectively. Conclusion:Ofloxacin is significantly and rapidly eliminated by CVVH with a high-flux polysulfone membrane.

Does Very Low Dialysis Endtoxin Level Influence the Plasma Pentosidine Levels in Dialysis Patients?

In order to confirm whether or not very low endtoxin level in dialysate influences the formation of advanced glycation end products (AGEs) in dialysis patients, plasma pentosidine were determined in the dialysis patients before and after the switch to new water-supply system. Method: Plasma pentosidine were measured by high-performance liquid chromatography in 84 patients on long-term hemodialysis before 3 month, 6 months after the switch of dialysate endtoxin level from 0.020–0.025 to 0.001 EU/ml. Endtoxin measurement was done by the Wellreader SK603 (Seikagaku Kogyo Co. Tokyo) by which detection limit is less than 0.001 EU/ml. The plasma pentosidine levels fell from 1.55 ± 0.61 nmol/ml to 1.38 ± 0.52 nmol/ml (3 month after, p < 0.0001) and 1.31 ± 0.50 nmol/ml (6 month after, p < 0.0001). The fall in plasma pentosidine levels were equally observed in patients given dialysis with high-flux polysulfone, PMMA, and cellulose acetate membranes. Unexpectedly, the plasma triglycerides levels fell from 150 ± 116 mg/dl to 124 ± 79 mg/dl (3 month after, p < 0.01) and 119 ± 75 mg/dl (6 month after, P < 0.01). The levels of total cholesterol, c-reactive protein, β 2-microglobulin did not change during this study. Conclusion: Water purity of dialysis fluid has an impact on AGE formation and improve a status of lipid metabolism in hemodialysis patients even if endtoxin level was very low.

Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in end-stage renal disease patients.

Free immunoglobulin light chains (FLCs) have previously been shown to be uraemic toxins. In this work we investigated the effect of haemodialysis and haemodiafiltration on the level of FLCs in serum/plasma of uraemic patients. Serum/plasma proteins were separated by non-reducing SDS-PAGE and transferred to a nitro-cellulose membrane. FLCs were detected by specific antibodies and an enhanced chemiluminescence detection system. The FLC concentrations were calculated. We studied 15 healthy subjects, 10 patients with chronic renal failure, 71 patients undergoing haemodialysis treatment and 33 patients treated with haemodiafiltration. Different membranes were compared: low- and high-flux polysulfone membranes, low- and high-flux cellulose triacetate membranes, high-flux polymethylmethacrylate and polyacrylonitrile membranes. Chronic renal failure patients showed elevated FLC concentrations as compared with controls. In haemodialysis or haemodiafiltration patients these values were even higher. This was mainly due to an increased concentration of FLC of the lambda-type. The treatment modality per se did not influence the FLC concentrations. Only haemodialysis or haemodiafiltration with the polymethylmethacrylate membrane lead to a significant reduction in FLC concentrations; however, these did not reach control levels. We did not observe differences in FLC levels between patients with different underlying diseases, nor did we find a correlation between age or the duration of the dialysis treatment and FLC concentrations. We found a positive correlation between FLC concentrations at the beginning of dialysis treatment and the amount of IgLCs removed during treatment. However, the average FLC level after treatment did not reach control values. Currently available haemodialysis or haemodiafiltration treatments are unable to normalize the elevated serum/plasma levels of FLCs in end-stage renal disease patients.