Removal of acyclovir during continuous veno-venous hemodialysis and hemodiafiltration with high-efficiency membranes

We present a critically ill patient with severe renal failure and anuria who underwent hemodialysis (HD), continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF) at different occasions, with 2 commonly used high-efficiency dialyzers (F-8 and CA-210), while receiving i.v. acyclovir. We estimate that during 24 hours of CVVHD with F-8 dialyzer approximately 18% and during 24 hours of CVVHDF with CA-210 dialyzer approximately 65% of the daily administered acyclovir is removed. This is comparable to the amount removed during 4 6 hours of HD, as reported previously. The percentage acyclovir extraction was 84% and 60% during CVVHD and CVVHDF with F-8 and CA-210 dialyzers, respectively. Acyclovir clearance during CVVHD was 14 ml/min and during CVVHDF was 17 ml/min, with F-8 and CA-210 dialyzers, respectively. Acyclovir half-life was 22.5 and 25.5 hours in 2 occasions off any type of renal replacement therapy, and it was 19.5 hours during CVVHDF with CA-210 dialyzer.     

Evaluation of Three Dry-Sterilized Hollow Fiber Artificial Kidneys

We investigated three new dry sterilized hollow fiber artificial kidneys (HFAK) (Cordis Dow CDAK 1.3, Travenol CF 1200, Extracorporeal Tri-Ex 1). Dry sterilization makes these dialyzers more economical by shortening set-up time. Dry sterilization also eliminates iatrogenic administration of residual sterilant. Water of imbibition can significantly increase the blood compartment volume of the dialyzer during dialysis. Consequently, a corrected blood volume for each dialyzer was established; these corrected volumes varied from 13-36% greater than the volume determined before dialysate flow. With low dose heparinization of these dialyzers there was between an 18 and 45% decrease in the post dialysis volume, presumably due to fiber clotting during dialysis. This volume added to the residual blood loss measured by a colori-metric technique accounted for a possible blood loss ranging between 26.9 and 53.9 ml per dialysis for these three dialyzers. Our results suggest that a relationship between dialyzer clotting and decreased dialyzer efficiency may exist. These three capillary flow dialyzers had a much lower platelet drop (0-9% pre to post) when compared to 30-40% drop of flat plate dialyzers. These dialyzers were found to be safe and easy to use but the high fiber clotting warrants further investigation in chronic dialysis patients on high dose heparin.     

Formation of Blood Foam in the Air Trap During Hemodialysis Due to Insufficient Automatic Priming of Dialyzers

We were encouraged to investigate the reasons for large amounts of foam observed in bloodlines during hemodialysis (HD). Foam was visible in the venous air trap within the Artis Gambro dialysis device. Estimates of the extent of foam were graded (0—no foam, 10—extensive foam) by two persons that were blind to the type of dialyzer used. Thirty‐seven patients were involved in the dialysis procedures. Consecutive dialyses were graded using dialyzers from Fresenius Medical Care (CorDiax dialyzers that were used for high flux HD—FX80 and FX100, and for hemodiafiltration—FX1000). The extracorporeal circuit was primed automatically by dialysate using Gambro Artis software 8.15 006 (Gambro, Dasco, Medolla Italy, Baxter, Chicago, IL, USA). The priming volume recommended by the manufacturer was 1100 mL, whereas our center uses 1500 mL. Extensive amounts of blood foam were visual in the air traps. Although the manufacturer recommended extension of priming volume up to 3000 mL, this did not eliminate the foam. Microbubble measurement during HD revealed the air to derive from the dialyzers. When changing to PF210H dialyzers (Baxter) and using a priming volume of 1500 mL, the foam was significantly less (P < 0.01). The extent of foam correlated with the size of the FX‐dialyzer surface (P = 0.002). The auto‐priming program was updated to version 8.21 by the manufacturer and the extent of foam in the air trap using FX dialyzers was now reduced and there was no longer a difference between FX and PF dialyzers, although less foam was still visible in the venous air trap during several dialyses. In conclusion, this study urgently calls attention to blood foam development in the venous air trap when using Artis devices and priming software 8.15 in combination with Fresenius dialyzers. Updated auto‐priming software (version 8.21) of Artis should be requested to reduce the extent of foam for the Fresenius dialyzers. Other interactions may also be present. We recommend further studies to clarify these problems. Meanwhile caution is warranted for the combined use of dialysis devices and dialyzers with incompatible automatic priming.     

Rapid removal of DFO-chelated aluminum during hemodialysis using polysulfone dialyzers

Aluminum (Al) removal following deferoxamine (DFO) therapy in hemodialysis patients was evaluated in a paired-fashion comparing cuprophane (Travenol 12.11) and polysulfone (Fresenius F-80) dialyzers. QB and QD were held constant at 250 and 500 ml/min, respectively. The polysulfone dialyzer increased total plasma Al clearance from 20.0 +/- 2.8 to 80.5 +/- 7.6 ml/min (P less than 0.01), and reduced the t 1/2 of plasma Al during hemodialysis from 538 +/- 113 to 112 +/- 12 min (P less than 0.01). The polysulfone F-80 dialyzer increased Al removal during the first hour of hemodialysis from 518 +/- 191 to 1812 +/- 720 micrograms/hr (P less than 0.01). During a four hour hemodialysis the F-80 dialyzer returned plasma Al levels to pre-DFO values (103 +/- 36 vs. 93 +/- 23, P less than 0.05), suggesting complete removal of the DFO chelated Al complex. In one patient Al removal was evaluated using cuprophane, F-40, F-60 and F-80 dialyzers and the t 1/2 for Al removed decreased from 484.6 to 276.1 and 108 to 99 minutes, respectively. These data show the Fresenius F-80 polysulfone dialyzer effects the rapid removal of DFO-Al complexes. We propose use of the Fresenius F-80 dialyzer in conjunction with reduced DFO doses and i.m. administration of DFO the day prior to dialysis to limit DFO exposure as a method to decrease DFO-related side-effects in hemodialysis patients.     

Symptoms and activation of granulocytes and complement with two dialysis membranes

Complement (C) activation, neutropenia, and mild pulmonary dysfunction attend hemodialysis (HD) with cellophane [for example, cuprophan (Cu)] membranes. While usually asymptomatic, these phenomena may cause distress in patients with cardiopulmonary disease, and "start-up" symptoms of HD might be mediated by C-stimulated granulocytes (PMNs). Cellulose acetate (CA) hemodialysis membranes have been devised and claimed more blood compatible than Cu. In a blinded series of HD patients, pruritus, fatigue, and sense of well-being were each scored statistically more favorably by the patients during HD with CA than during HD with Cu (P less than 0.05). Postulating that less C activation might underlie the benefit, we showed that neutropenia was less severe with CA (nadir 77.6% of initial count, +/- 4 SEM) than with Cu (38.3% +/- 2.9; P less than 0.01). In vitro, incubation of CA membranes with plasma led to less C3 conversion (20% vs. 40%), less PMN aggregating activity (5.9 ZAP units vs. 36.3) and less decrement in CH50 (6.5% vs. 22%) than like incubations of Cu. C activation was also less potent in vivo: During HD plasma C3a rose from a mean 401 ng/ml to a peak 6,325 in patients on Cu dialyzers, but from 426 to only 3,637 in patients on CA devices (P less than 0.05). Time-course studies suggested CA was initially as potent an activator as Cu but rapidly lost ability to activate C, possibly because of saturation of C3b binding sites. As an index of PMN activation, we also assayed plasma lactoferrin and found levels significantly higher during Cu than CA dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Technical and Clinical Data on High-Performance Hemofiltration: Twelve Patients During One Year

In 12 chronic hemodialysis patients, postdilutional hemofiltration (HF) was substituted for conventional acetate hemodialysis (HD) (4-5 h/session with high-area capillary dialyzers). In HF, the purposes were to obtain (a) no increase in pre-HF uremia compared with pre-HD uremia (high ultrafiltrate volume), (b) an HF duration shorter than that of HD (mean ultrafiltrate rate greater than 120 ml/min), (c) a disposable cost of an HF session identical to that of an HD session (reuse of hemofilters and extemporaneous preparation of substitution fluid). One-year results were (a) an ultrafiltrate volume of 26.8 L/session and a pre-HF uremia of 35.4 mmol/L (pre-HD uremia 34.0 mmol/L), (b) a mean ultrafiltrate rate of 143 ml/min and a mean HF duration of 190 min (mean HD session duration 250 min), and (c) better clinical tolerance and vascular stability in HF than in HD (weight loss 3.5 kg in HF and 3.0 kg in HD). Reuse of filters and extemporaneous preparation of substitution fluid were not responsible for any pyrogen reaction or bacterial contamination. In conclusion, (a) compared with conventional HD, high-flux HF results included identical removal of small molecules, improvement in vascular stability, decrease in session duration, and identical disposable cost; (b) routine high-flux HF is workable in a dialysis unit; (c) vascular access is the most important limiting factor to high-flux HF. Today 30-40% of patients can be treated with this method.     

Plasma adrenomedullin levels in patients on hemodialysis

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 +/- 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 +/- 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.     

Influence of Hemodialysis Membranes on Gene Expression and Plasma Levels of Interleukin-iβ

Abstract: Plasma levels of interleukin-iβ (IL-iβ) were measured in 10 normal subjects, in 11 nondialyzed end-stage renal failure (ESRD) patients, and in 22 hemodialysis (HD) patients. Of the HD patients, 7 were dialyzed with Cuprophan (CU), 7 with polymethylmethacrylate (PMMA), and 8 with polysulphone (PS) dialyzers. In normal controls, nondialyzed ESRD patients, and HD equipped with CU, PAMM, and PS dialyzers, plasma levels of IL-iβ were 10.73 ± 5.24 pg/ml, 9.97 ± 3.61 pg/ml, 13.17 ± 4.04 pg/ml, 15.16 ± 6.16 pg/ml, and 13.96 ± 5.47 pg/ml, respectively. There were no statistically significant differences among the groups (p ≥ 0.05). In contrast, the gene expression of IL-iβ for peripheral blood mononu-clear cells (PBMC) by in situ hybridization showed differences among the groups. The gene for IL-iβ for PBMC appears in HD equipped with different membranes, but not in cases of nondialyzed uremic patients and normal subjects. With computer imaging analysis, we carried out quantitative analysis of cells in in situ hybridization with an area of positive spots to an area of total cells. In HD with CU, PMMA, and PS, the results were 10.64 ± 1.07, 3.34 ± 0.74, and 3.27 ± 0.64%, respectively. The levels of IL-iβ gene expression in CU were higher than that in PMMA or PS. There were statistically significant differences (p ≤ 0.001) between CU and PMMA or PS and no significant difference between the PMMA and PS (p ≥ 0.05). We suggest measuring the gene expression of cy-tokines for PBMC and which may be better than measuring cytokine levels only for investigating the blood compatibility of dialyzers, which may help in understanding chronic complications of the dialysis procedure.     

Cuprophan reuse and intradialytic changes of lung diffusion capacity and blood gases

The changes in arterial blood gas, pulmonary function tests, leukocyte counts and complement activation were evaluated during first use and subsequent reuse of cuprophan dialyzers. The dialysate buffer was bicarbonate. Reuse of cuprophan dialyzers significantly attenuated the fall in leukocyte counts and the rise in C3a des Arg seen during first use dialysis. First use dialysis also caused a drop in arterial paO2 from 93.0 +/- 12.4 mm Hg to a nadir of 82.8 +/- 12.6 mm Hg at 60 minutes (P less than 0.01). PaO2 levels did not change when reused dialyzers were employed (93.7 +/- 12.2 before dialysis and 96.4 +/- 15.2 mm Hg at 60 minutes, P greater than 0.05). Intradialytic paO2 curves obtained during first use and reuse were significantly different by variance analysis (P less than 0.001). There was also a significant decline in lung diffusion capacity (DLCO, from 30.70 +/- 8.89 to 23.77 +/- 7.76 ml/min X mm Hg, P less than 0.01) and transfer factor (KCO, from 6.07 +/- 1.97 to 5.65 +/- 2.13 ml/min X mm Hg, P less than 0.01), during first use at one hour after initiation of dialysis. This decrease was entirely prevented during reuse, (P less than 0.001 vs. first use by variance analysis). Percentual changes in leukocyte counts and C3a des Arg concentration on one hand, and in paO2, DLCO and KCO on the other were significantly correlated to each other. Other factors with a possible influence on intradialytic pulmonary function such as ultrafiltration volume, dialysate buffer composition, evolution of intradialytic blood pH and cardiac output, were all identical under both experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of insulin adsorption behavior of dialyzer membranes used in hemodialysis

Although it has been reported that plasma insulin is removed by hemodialysis (HD), the mechanism for this has not been elucidated. We investigated the mechanism of insulin removal during HD treatment and the characteristics of insulin removal with three high-flux membranes. In our in vivo study, 20 stable diabetic patients on HD were randomly selected for three HD sessions with three different membranes: polysulfone (PS), cellulose triacetate (CTA), and polyester polymer alloy (PEPA). Blood samples were obtained from the blood tubing at the arterial (A) site at the beginning and end of the sixth HD session to investigate insulin reduction in patients. At 1 h after the initiation of dialysis, blood samples were obtained from both the A and venous sites of the dialyzer to investigate the insulin clearance with the different membranes. There was a significant reduction in patients' plasma insulin at each time point with each of the three membranes. The insulin clearance with the PS membrane was significantly higher than that with the CTA and PEPA membranes. Although no difference was observed in the plasma insulin reduction rate between the three membranes in the total subject group, there was a significantly higher reduction rate with the PS membrane in insulin-dependent diabetes mellitus subjects. The clearance of insulin in in vitro tests was significantly higher with the PS and PEPA membranes than with the CTA membrane in both new and clinically used dialyzers. Insulin was not detected in the dialysate or ultrafiltration fluids in either the in vivo or in vitro studies. The mechanism of plasma insulin clearance by HD is mainly by adsorption, and the amount of insulin adsorbed differed depending on the dialyzer membrane used.     

The Effects of Endotoxin–Contaminated Dialysate and Polysulfone or Cellulosic Membranes on the Release of TNFα during Simulated Dialysis

Abstract: Simulated dialysis of whole blood was used to determine whether membrane factors (biocompatibility), endotoxin (ET) membrane diffusion, or transmembrane monocyte–ET interactions would stimulate tumor necrosis factor (TNFα) release. Whole blood containing EDTA and aprotinin was recirculated in the blood compartment of hollow fiber dialyzers containing either regenerated cellulose or polysulfone membranes. ET–free and ET–spiked dialysate were recirculated consecutively in the dialysate compartment for 30 min each. Blood and dialysate samples were collected at t _o and after each 30 min of simulated dialysis for determination of TNFa and ET concentrations. TNFa was not detected in any blood samples collected after simulated dialysis with regenerated cellulose (RC) membranes and ET–free or ET–spiked dialysate. However, blood ET concentrations, as determined by the Limulus amebocyte lysate (LAL) assay, increased in RC dialyzers after each 30 min of simulated dialysis even with ET–free dialysate. Since TNFa was not detected in these blood samples, the material detected by the LAL assay probably was not ET but an LAL–reactive material. After simulated dialysis with polysulfone dialyzers and ET–free dialysate, TNFa and ET were not detected in blood samples. ET also was not detected in blood samples after dialysis with ET–spiked dialysate. However, TNFa was detected in 7 of 13 (54%) of the blood samples following the 500 ng/ml of ET dialysate spike. TNFα release during simulated dialysis with polysulfone membranes and ET–contaminated dialysate may be due to transmembrane stimulation of circulating mononuclear cells and not diffusion of ET across the membrane.     

Effect of sympathetic and plasma renin activity on hemodialysis hypertension

BACKGROUND: The reasons for poor control of blood pressure in hemodialysis (HD) patients are not clear, while patients have achieved their desirable dry weight and excess weight are not different between the hypertensive and normotensive patients. A link between sympathetic activity and HD hypertension could be an alternative explanation. PATIENTS AND METHODS: We studied the effect of sympathetic and plasma renin-aldosterone activity of 10 hypertensive patients, 5 men and 5 women, aged from 30 to 60 years. The results were compared to those of another 10 normotensive hemodialysis patients. Blood samples were taken before HD and at the end of a 4-hour HD session for plasma aldosterone (ALDO), renin activity (PRA), adrenaline and noradrenaline determination. One month dialysis records, which includes 13 dialysis sessions and 26 blood pressure readings for each patient were used, for pre-dialysis and post dialysis mean arterial blood pressure (MAP) measurement. RESULTS: Pre-dialysis plasma adrenaline was 124.12 +/- 12.93 pg/ml vs. 121.12 +/- 14.71 pg/ml and plasma noradrenaline was 260.88 +/- 140.86 pg/ml vs. 138.11 +/- 122 +/- 32 pg/ml for hypertensive and normotensive patients, respectively. Post-dialysis plasma adrenaline and noradrenaline levels were 119.37 +/- 8.81 pg/ml vs. 120.62 +/- 15.35 pg/ml and 210.44 +/- 126.71 pg/ml vs. 94.88 +/- 64.05 pg/ml for hypertensive and normotensive patients, respectively. Pre-dialysis PRA was 8.70 +/- 6.37 ng/ml/h vs. 2.77 +/- 1.8 ng/ml/h and plasma ALDO was 457.07 +/- 245.54 pg/ml vs. 197.74 +/- 87.46 pg/ml for hypertensive and normotensive patients, respectively. Pre-MAP was 109.76 +/- 5.21 mmHg vs. 99.28 +/- 7.13 mmHg and post-MAP was 107.22 +/- 6.74 mmHg, vs. 91.61 +/- 7.27 mmHg for hypertensive and normotensive patients, respectively. Plasma ALDO and fluid volume removed by ultrafiltration were found to be significantly correlated (p < 0.05). PRA and plasma adrenaline-noradrenaline levels were not correlated with MAP or body weight alterations. CONCLUSIONS: It is suggested that sympathetic activity, as it was expressed by plasma catecholamine alterations, is not associated with hemodialysis hypertension.     

Activation of coagulation during hemodialysis: effect of blood lines alone and whole extracorporeal circuit

Activation of coagulation during hemodialysis (HD) is a relevant clinical problem, especially when patients at risk of bleeding are treated. However, little is known about the relative contribution of the various components of the circuit to the thrombotic process. Thus, an experimental model was developed that is aimed at evaluating biochemical markers of coagulation activation at different times and sites throughout the HD circuit. A HD blood-tubing set with integrated arterial and venous chambers (cartridge-line set) was used, which was added with the following sampling points: at the beginning of the arterial line (P1), before the blood pump (P2), after the blood pump (P3), and at the end of the venous line (P4). A bypass system allowed us to circulate the blood only into the blood lines for the first 20 min of the extracorporeal circulation. The extracorporeal circuit was rinsed with 1.7 L of heparinized saline (2,500 IU/L) that was completely discarded before patient connection. A continuous administration of unfractionated heparin (500-800 IU/h) without a starting bolus was adopted as a low heparin extracorporeal treatment. Samples were collected before the start of the extracorporeal circulation from the fistula needle (T0P0), after 5 (T1), 10 (T2), and 20 min (T3) from P1, P2, P3, and P4. After 20 min, the blood was returned to the patient using only saline and HD was then started, circulating the blood through the dialyzer. Further samples were obtained from P1 and P4 after 5 (T4) and 210 min (T5). Plasma levels of coagulation activation markers-thrombin-antithrombin complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2)-were evaluated in all the samples in 12 stable HD patients. In each patient, the activated partial thromboplastin time (APTT) was measured at T0P0 and T1-T5 from P1. No significant changes were found at any time as far as F1 + 2 is concerned. However, TAT levels increased over time only after the start of HD, suggesting that the latter test could be more useful in order to detect coagulation activation during HD. The same experiments performed with nonheparin-primed extracorporeal circuit showed similar results. The blood lines used did not significantly activate coagulation during the first 20 min, whereas only 5 min of blood circulation throughout the whole circuit increased TAT values, which still remained lower than previous reports, even after 210 min of treatment.     

Residual Formaldehyde in Dialyzers: Quantity, Location, and the Effect of Different Methods of Rinsing

When formalin-sterilized dialyzers were rinsed by our standard technique (similar to that used in many other dialysis centres) undesirable concentrations of formaldehyde were found in the dialyzers at the start of dialysis. When the technique was modified by passing part of the saline through the blood compartment immediately before connection and discarding the saline left in the dialyzer at the time of connection, the concentration of formaldehyde infused into the patient fell below 2 μg/ml. However, the dialyzers still contained up to 13 mg of formaldehyde which leached slowly from the dialyzer during simulated dialysis. Some residual formaldehyde was found in several components of the dialyzer but the great majority was contained in the cellulose membrane.     

Net Ultrafiltration May Not Eliminate Backfiltration During Hemodialysis with Highly Permeable Membranes

Backfiltration of dialysis solution can occur during hemodialysis with highly permeable membranes. A method has recently been developed for determining backfiltration rates in vitro at low dialysate flow rates by measuring changes in the local dialysate concentration of a marker macromolecule via sampling ports added to the hemodialyzer housing. In the present study, the influence of net ultrafiltration on backfiltration rates was determined for five commercial dialyzers containing membranes with different water permeabilities. In vitro experiments were performed (n = 3) using freshly donated whole blood at blood flow rates of 200 and 340 ml/min and at a dialysate flow rate of 100 ml/min. At zero net ultrafiltration, backfiltration rates increased with increasing membrane water permeability and ranged from 0.9 to 6.9 ml/min. At a net ultrafiltration rate of 10 ml/min, backfiltration was eliminated for dialyzers containing membranes with water permeabilities of less than 30 ml/h/mm Hg but remained significant for dialyzers with higher membrane water permeabilities. Therefore, despite a significant net ultrafiltration rate, backfiltration may still occur during hemodialysis with highly permeable membranes.     

Warning of high-flux hemodialysis.

In order to estimate the influence of flux on plasma refilling during hemodialysis (HD), prospective crossover studies were performed in 10 HD patients with low-flux and high-flux dialyzers. Hematocrit was continuously monitored to assess changes in blood volume. In addition, plasma osmolarity and total protein concentration were measured. Intradialytic reductions in body weight (-5 +/- 1 vs -5 +/- 1%) and plasma osmolarity (-5 +/- 1 vs -5 +/- 1%) were similar in both conditions. Although mean blood pressure remained unchanged in either state, the decrease in blood volume was larger in high-flux HD (-13 +/- 2 vs -10 +/- 2%, p<0.05). In spite of greater contraction in blood volume during high-flux HD, total proteins were increased equally between low-flux and high-flux HD (11 +/- 4 vs 11 +/- 4%). Our data that although high-flux HD failed to induce significant drops in blood pressure, it elicited greater magnitude of decreases in blood volume, implicate the judicious application of high-flux HD.     

WARNING OF HIGH-FLUX HEMODIALYSIS

In order to estimate the influence of flux on plasma refilling during hemodialysis (HD), prospective crossover studies were performed in 10 HD patients with low-flux and high-flux dialyzers. Hematocrit was continuously monitored to assess changes in blood volume. In addition, plasma osmolarity and total protein concentration were measured. Intradialytic reductions in body weight (?5 ± 1 vs ?5 ± 1%) and plasma osmolarity (?5 ± 1 vs ?5 ± 1%) were similar in both conditions. Although mean blood pressure remained unchanged in either state, the decrease in blood volume was larger in high-flux HD (?13 ± 2 vs ?10 ± 2%, p < 0.05). In spite of greater contraction in blood volume during high-flux HD, total proteins were increased equally between low-flux and high-flux HD (11 ± 4 vs 11 ± 4%). Our data that although high-flux HD failed to induce significant drops in blood pressure, it elicited greater magnitude of decreases in blood volume, implicate the judicious application of high-flux HD.     

Improvement of Intradialytic Hypotension in Diabetic Hemodialysis Patients Using Vitamin E‐Bonded Polysulfone Membrane Dialyzers

Currently, there are no detailed reports on the effects of vitamin E‐bonded polysulfone (PS) membrane dialyzers on intradialytic hypotension (IDH) in diabetic hemodialysis (HD) patients. This study was designed to evaluate changes in intradialytic systolic blood pressure (SBP) using “VPS‐HA” vitamin E‐bonded super high‐flux PS membrane dialyzers. The subjects were 62 diabetic HD patients whose intradialytic SBP fell by more than 20%. Group A comprised patients who required vasopressors to be able to continue treatment or who had to discontinue therapy due to their lowest intradialytic SBP being observed at 210 min (28 patients). Group B comprised patients who showed no symptoms and required no vasopressors but showed a gradual reduction in blood pressure, with the lowest intradialytic SBP seen at the end of dialysis (34 patients). The primary outcome was defined as the lowest intradialytic SBP after 3 months using VPS‐HA. Secondary outcomes included changes in the following: lowest intradialytic diastolic blood pressure, pulse pressure, pulse rate, plasma nitric oxide and peroxynitrite, serum albumin, and hemoglobin A1c. Group A's lowest intradialytic SBP had significantly improved at 3 months (128.0 ± 25.1 mm Hg vs. 117.1 ± 29.2 mm Hg; P = 0.017). Group B's lowest intradialytic SBP had significantly improved at 1 month (134.4 ± 13.2 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.047) and 3 months (139.1 ± 20.9 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.011). We conclude that VPS‐HA may improve IDH in diabetic HD patients.     

Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients.

BACKGROUND: Enhanced oxidative stress in haemodialysis (HD) patients may be considered as a risk factor for accelerated atherosclerosis. Reduced antioxidant defences include impairment in enzyme activities and decreased plasma levels of hydrophilic vitamin C (vit C), and cellular levels of lipophilic vitamin E (vit E). METHODS: We investigated plasma levels of vit C in 19 patients undergoing regular haemodiafiltration (HDF) (mean age 62+/-7 years) and in 1846 healthy elderly subjects (HS) (mean age 69+/-5 years). The contribution of convection and diffusion was determined using paired filtration dialysis (PFD), a modified HDF technique which physically separates convective from diffusive fluxes. Blood samples were collected before and after the HDF session; in addition at 60 min of HDF, samples were drawn from arterial lines (AL) and venous lines (VL), dialysate (D) and ultrafiltrate (UF). Blood levels of total vit C were determined using an HPLC fluorescence method. Markers of oxidative stress were also assessed in both populations as follows: levels of malondialdehyde (MDA) were determined by fluorometric assay, measurements of advanced oxidation protein products (AOPP) and glutathione peroxidase (GSH-Px) activity were performed by spectrophotometric assay, and plasma vit E content was obtained by an HPLC procedure. RESULTS: A significant reduction in plasma vit C level was observed in HDF patients when compared with HS (1.6+/-1.4 microg/ml in HDF vs 6.6+/-3.7 microg/ml in HS; P<0.01). The HDF session was associated with a dramatic reduction in vit C levels (1.87+/-1.57 microg/ml before HDF and 0.98+/-0.68 microg/ml after HDF); at 60 min of HDF, concentrations were as follows: AL=1.35+/-1.27 microg/ml; VL=0.37+/-0.31 microg/ml, D=0.40+/-0.34 microg/ml, UF=1.24+/-1.18 microg/ml; corresponding to a diffusive flux of 271 microg/min and a convective flux of 126 microg/min. Total loss of vit C could be assessed at 66 mg/session (8--230 mg/session). According to this loss of vit C, presence of an oxidative stress was demonstrated in HD population as shown by a significant increase in MDA (1.66+/-0.27 microM in HD vs 0.89+/-0.25 microM in HS; P<0.01) and AOPP (77.5+/-29.3 microM in HD vs 23.5+/-13.2 microM in HS; P<0.01) levels, and a decrease in GSH-Px activity (259.2+/-106.3 U/l in HD vs 661.2+/-92.2 U/l in HS; P<0.01). No change in plasma vit E between both populations (30.7+/-9.1 microM in HD vs 35.3+/-7.34 microM in HS) was observed. CONCLUSIONS: These results suggest that HDF with highly permeable membranes is associated with a significant loss of vit C. Diffusive transport is responsible for two-thirds whereas convective phenomenon accounts for only one-third of this loss.     

Complement Activation During Hemodialysis: Clinical Observations, Proposed Mechanisms, and Theoretical Implications

Abstract: Human C3a radioimmunoassay techniques were employed to define both the temporal profile and the amount of complement activation taking place in the extracorporeal circuit during maintenance hemodialysis. Prospective studies demonstrated that C3a formation, like hemodialysis-associated leukopenia, was a transient phenomenon that occurred predominantly during the first 30 min of dialysis. Quantitative comparisons revealed that new Cuprophan hemodialyzers displayed somewhat greater complement-activating potential than cellulose acetate dialyzers. By contrast to new Cuprophan membranes, both reused Cuprophan and polyacrylonitrile dialyzers exhibited only a modest ability to activate human complement. These findings are compatible with the known mechanisms of complement activation and suggest that certain chemical and biochemical methods might be exploited to enhance the biocompatibility of cellulose dialysis membranes.