Hemophan Membranes Research Articles

Increased Exhaled H2O2 and Impaired Lung Function in Patients Undergoing Bioincompatible Hemodialysis

Chronic renal failure (CRF) and hemodialysis (HD) accumulate an inflammatory milieu, contributing to increased systemic and airway oxidative stress that may lead to lung damage. This study was designed to assess exhaled hydrogen peroxide (H2O2), lung function and whole blood chemiluminescence in HD and CRF patients and healthy controls. The study included 59 patients (Polyamide STM or Hemophan membranes--19, cuprophane--16, hemodiafiltration--14, continuous ambulatory peritoneal dialysis--10), 16 CRF and 16 healthy controls. The assessment of lung function included FVC (forced vital capacity), FEV1 (forced expiratory volume in the first second) and DLCOc (single breath CO diffusing capacity). Exhaled H2O2 was determined fluorometrically and resting and n-formyl-methionyl-leucyl-phenylalanine (fMLP) luminol-dependent whole blood chemiluminescence (LBCL) were measured simultaneously. Only cuprophane HD patients presented decreased lung function (FVC 63.8+/-17.4%, FEV1 55.9+/-20.3 and DLCOc 72.1+/- 9.3 % of predicted; p<0.05 vs. controls). These patients exhaled the highest H2O2 levels in comparison to CRF (p<0.01): median 0.36 microM (range R: 0.09-0.56 microM) and controls (p<0.05): 0.17 microM (0.2-17.8 microM). These levels were not decreased during the HD session: preHD 1.25 microM (0.2-16.5 microM) and postHD 1.3 microM (0.2-17.8 microM). As a marker of systemic oxidative stress, fMLP-induced LBCL (total light emission) was increased in these patients (1570.6 aUxs/10(4) phagocytes; R: 274.2-8598.9) and in the CRF group (2389.4 aUxs /10(4) phagocytes; R: 491.5- 6184; p<0.05 vs. controls). Other patient groups did not express elevated LBCL and revealed decreased exhaled H2O2 after a session. An increased oxidative burden in the lungs may contribute to functional lung impairment in patients dialyzed with a cellulose membrane. Biocompatible dialysis with other modalities might reduce airway-borne oxidative stress and is not related with lung damage.

The role of interleukin-6 and of its soluble receptors in the biocompatibility of dialysis treatment

Proinflammatory cytokines, in addition to their role in host defence, may be considered mediators of disease; a reduction of cytokine synthesis or effects is, therefore, becoming a target of many diseases. IL-6 is a pro-inflammatory cytokine that may play a role in several clinical problems related to dialysis treatment. An enhanced spontaneous production of IL-6 by Peripheral Blood Mononuclear Cells (PBMC) harvested from ESRD patients dialyzed with a poor biocompatible membrane has been first demonstrated by our group. These results were also obtained in patients undergoing continuous peritoneal dialysis, in absence of peritonitis. We have also demonstrated that IL-6 release was inversely correlated with serum albumin changes. Biological activities of IL-6 may be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R may enhance the inflammatory effects of IL-6 and is, therefore, an "agonistically" acting molecule. We have recently studied sIL-6R production in ESRD patients dialyzed with different membranes; the conclusion was that poor biocompatible membranes, via the sIL-6R, might further increase the inflammatory effects of IL-6. On the contrary, sgp130 can efficiently bind the IL-6/sIL-6R complex with "antagonistic" effects. We have evaluated plasma levels of sgp130 in 18 ESRD patients regularly dialyzed with hemophan membranes (HE) and in 15 patients dialyzed with more biocompatible synthetic membranes (BIO). Our results demonstrate that plasma levels of sgp130 in HE are 33% higher than in both healthy controls and BIO. Circulating levels of sgp130 were correlated positively with C-reactive protein (r: 0.338, p<0.05) and negatively with serum albumin (r: -0.334, p<0.05). These results suggest that higher circulating levels of sgp130 are likely associated with higher IL-6 levels. These higher amounts are probably insufficient to control the activity of IL-6 and may be considered only as a marker of PBMC activation.

Vitamin E-bonded hemodialyzer improves neutrophil function and oxidative stress in patients with end-stage renal failure

We evaluated the biocompatibility of a newly developed vitamin E hemodialyzer (CL-EE; Terumo Co Ltd, Tokyo, Japan) by neutrophil function and oxidant stress in patients with end-stage renal failure in a randomized crossover study. Ten patients underwent hemodialysis using either the CL-EE or a control dialyzer membrane identical to the CL-EE except for vitamin E binding for 12 weeks in a crossover fashion after a 1-month washout period with hemophane membranes. White blood cell counts, serum oxidized low-density lipoprotein (Ox-LDL) levels, and malondialdehyde (MDA) levels during hemodialysis sessions were measured at the initiation and end of the CL-EE and control trials. Superoxide anion production by neutrophils just before and 4 hours after starting the session also was measured. Leukocytopenia at 1 hour after starting the session was detected to a similar extent in both membranes. However, the degree of reduction was less in the CL-EE trial after repeated use. Superoxide anion production by neutrophils just before a hemodialysis session was reduced after repeated use of the CL-EE membrane. Serum Ox-LDL levels increased, whereas serum MDA levels decreased during sessions to a similar extent in both trials. However, these parameters were significantly lower in the CL-EE trial after repeated use. Serum LDL concentrations significantly decreased with repeated use of the CL-EE membrane. These data suggest that repeated use of the CL-EE membrane for 3 months improves neutrophil function, oxidant stress, and LDL concentrations in patients with renal failure. This membrane may be useful to reduce the incidence of cardiovascular events in patients with renal failure.

Long Nocturnal Dialysis

Background/Aims: The continuous growth of the dialysis pool in our unit induced us to organize a third long nocturnal dialysis (LND) session, considering the excellent survival and rehabilitation results reported with this method. This paper analyzes the results and assesses the role of LND among the different dialytic treatment options. Methods: Out of 18 patients on LND, 13 (12 males and 1 female, mean age 52 ± 13 years, time on dialysis 21.8 ± 23.8 months) with >6 months’ experience were studied, and 9 underwent a further metabolic evaluation. LND was performed using 1- to 1.4-m² Hemophan membranes, bicarbonate buffer, 200–250 ml/min blood flow, and 300–500 ml/min dialysate flow, 8 h three times a week. Kt/V and protein catabolic rate (3-point classic urea kinetics), postdialytic weight, serum albumin, total protein, hemoglobin, Ca²⁺, phosphate, intact parathyroid hormone, bioimpedance body water, blood pressure, and drug use (antihypertensives, phosphate binders, erythropoietin, vitamin D, hypnotics) were evaluated in each patient during hemodialysis and LND. In the metabolic study (done twice), sodium (compared with the Kimura model), potassium, phosphate, and urea were analyzed in blood and inlet and outlet dialysate after 0, 2, 4, 6, and 8 h. Results: The mortality was low (1 death every 247 patient-months). After 19 ± 8.1 months of LND, the postdialytic weight rose from 68.5 ± 9.6 to 70.8 ± 10.7 kg (p ≤ 0.01), and the hemoglobin concentration rose from 10.8 ± 2.2 to 11.8 ± 1.8 g/dl (p ≤ 0.05); phosphate dropped from 5.6 ± 2.0 to 4.4 ± 1.3 mg/ dl (p ≤ 0.01) and the systolic blood pressure from 152 ± 15 to 143 ± 19 mm Hg (p ≤ 0.05). In the metabolic study, the sodium profile was significantly lower during the last 4 h than in the Kimura model. The potassium concentration, stable between 4 and 6 h, rose against the gradient during the last 2-hour period. The behavior of sodium and potassium during the last part of the dialysis session can be taken to indicate exhaustion of the sodium/potassium pump. Phosphate showed a gradual reduction with no intradialytic and only a moderate postdialytic rebound. The postdialytic urea rebound was 23.4%. Conclusions: LND is a useful additional tool for nephrologists in treating chronic renal failure, it is easy to organize, and it shows overall good results. Together with other dialysis methods, this schedule permits individualized treatment for each uremic patient.

Electrical Current Leakage during Hemodialysis May Increase Blood-Membrane Interaction

During hemodialysis blood - membrane interaction causes complement activation. During dialysis there may be an electrical current leakage to the dialyzer, especially if there is a broken ground or a defect in another electrical device coupled to the patient. This study investigated whether an electric current of 1.5 mA DC could alter blood membrane interaction as measured by changes in C3d in the blood. Such a high current leakage could occur because there is no protection in the dialysis machine (Class 1B) against auxiliary current leakage. Such a current could come from a defective external device in contact with the patient during hemodialysis. A dialysis machine (Fresenius 2008C) with a filled blood-line system containing about 350 ml whole blood from each of 8 different donors was used in vitro. Each of the eight test-runs also contained 1000 U added heparin. The dialysis procedure was performed using hemophan membranes (GFS + 12, Gambro) with bicarbonate and potassium 3.0 (D210, Gambro) as dialysate. Two electric poles were placed in the blood line, before and after the dialyzer (connected in parallel) and the ground was placed at entry and exit of the dialysate fluid coming from the machine to the dialysis filter. C3d was measured before the start of "dialysis" and at 15, 30, 45 and 60 min, during dialysis. Thereafter the 1.5 mA current was switched on and additional samples were drawn at 75 and 90 min. The mean C3d values were calculated. Paired non-parametric statistical analyses were performed. There was a significant and continuous increase in C3d as compared to the "predialysis" level. The increase during 0 to 30 minutes was greater than that from 30 to 60 minutes (p=0.018); the increase in C3d during 60 to 90 min, was greater than that from 30 to 60 min (p=0.018) and there was no difference between the 0 to 30 and the 60 to 90 min increases. A current, used in this study, was able to induce a blood membrane interaction during in vitro dialysis. Even a weaker current leakage might have such adverse effects and similar interactions seem possible during regular dialysis depending on the extent of the leakage.

Dutch Society of Nephrology 60th Scientific Meeting. Maastricht, The Netherlands. October 11th, 1998

It is well known that the use of low temperature (T) dialysate can have a positive impact on hemodynamic stability during HD. However, little is known on the energy transfer (ET) from the extracorporeal system to the patient in relation to variations in dialysate T (Tdial). In this study, we assessed ET, body T (Tbody), and blood pressure (BP) during dialysis with normal Tdial (37.5 degrees C) and low Tdial (35.5 degrees C). Nine patients (4 males, 5 females; mean age 68 +/- 10 years) were studied with the patient as his/her own control. Bicarbonate was used as dialysate buffer. Hemophane membranes were used. Dialysis contained <100 CFU/mL. Ultrafiltration volume was comparable between the 2 treatment sessions. ET was assessed by continuous measurement of T in the arterial (Tart) and venous side (Tven) of the extracorporeal system (Fresenius BTM(R)) according to the formula: ET = (Tven - Tart) * blood flow * treatment time * specific thermal capacity (3.64 kJ/kg* degrees C) * blood density (1052 kg/m3). RESULTS: Results: mean+/-SD Tdial 37.5 Tdial 35.5 p Delta Syst BP mmHg -43 +/-21 -22 +/-26 <0.05 Delta Dias BP mmHg -15 +/-10 0 +/-19 0.07 Tbody before HD ( degrees C) 36.7 +/-0.3 36.4 +/-0.6 NS Tbody after HD ( degrees C) 37.2 +/-0.2 36.4 +/-0.3 <0.001 Tven after HD ( degrees C) 36.7 +/-0.1 35.0 +/-0.2 <0. 001 ET (kJ) -86 +/-43 -286 +/-74 <0.001 CONCLUSION: Tbody remained stable during Tdial = 35.5 degrees C despite significant energy loss and increased during Tdial = 37.5 degrees C despite netto ET from the patient to the extracorporeal system. The latter suggests that HD itself leads to intrinsic heat generation in the patient. The removal of this excess heat in combination with the cardiovascular response to maintain Tbody may be responsible for the beneficial hemodynamic effects of low Tdial.

Postdialysis urea rebound: Determinants and influence on dialysis delivery in chronic hemodialysis patients

We measured postdialysis urea rebound (PDUR) 30 minutes after dialysis in 92 chronic hemodialysis patients. The impact of PDUR on the estimation of dialysis delivery assessed by urea reduction ratio and Kt V was evaluated. Total recirculation, access plus cardiopulmonary, was measured at the end of dialysis with the two-needle low blood flow method. The mean age of the 92 patients (49 men and 43 women) was 59.6 ± 1.4 years. Thirty-eight patients had been receiving erythropoietin therapy for more than 3 months. Fifteen patients had central venovenous access and 77 had peripheral arteriovenous access. Sixty-five patients were dialyzed using hemophan membranes and 27 were dialyzed using polyacrylonitrile membranes. The mean blood flow rate was 240 ± 28 mL/min and the mean length of the hemodialysis sessions was 3.6 ± 0.1 hours. Kt V was calculated with Daugirdas' second-generation formula. The mean PDUR was 16.6% ± 0.8% (range, 2% to 44%) (n = 92), and significantly decreased the mean urea reduction ratio from 61.7% ± 0.8% to 55.5% ± 0.9%, the mean Kt V from 1.14 ± 0.03 to 0.97 ± 0.02, and the mean protein catabolic rate from 1.06 ± 0.04 to 0.98 ± 0.02 ( P = 0.0001). The effective Kt V at 30 minutes postdialysis was well predicted by using a recently proposed equation: eKt V 30 = Kt V sp − (0.6 × (0.6 × Kt V spt + 0.03, with a mean value corresponding also to 0.97 ± 0.02. However, this estimation was less predictive in patients with very high PDUR. Moreover, PDUR showed only a weak negative correlation with dialysis session length ( r = −0.28) and predialysis patient weight ( r = −0.29), and showed no correlation with predialysis serum urea level or with blood flow rate. However, dialysis efficiency, as assessed by K V , presented a correlation of 0.54 with both PDUR and the difference in Kt V when using urea immediately postdialysis and at 30 minutes. The mean total recirculation was 7.4% ± 0.6% (n = 86). Postdialysis urea rebound, calculated between 30 or 120 seconds and 30 minutes after dialysis to deduce the influence of recirculations, was reduced but remained important with a mean of 11.8% ± 0.7%. Thus, total recirculation contributed to nearly 30% of PDUR. The 24 patients with PDUR ≥20% were compared with the 68 patients with PDUR lower than 20%: women and patients with higher K V and higher total recirculation presented greater PDUR. Because of relatively few predictive factors for PDUR, its potential considerable impact on dialysis delivery estimation, and the influence of recirculations on the total PDUR amount, total recirculation and PDUR should be determined on an individual basis in chronic hemodialysis patients. The equation proposed to estimate effective Kt V at 30 minutes is accurate in most patients with PDUR lower than 30% and is a simple alternative.

Beta-2-microglobulin and main granulocyte components in hemodialysis patients.

Plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1-PI) increased during hemodialysis from 110 +/- 10 to 506 +/- 66 micrograms/L using dialyzers made of polyamide, from 95 +/- 2.2 to 211 +/- 54 micrograms/ml with hemophane and from 114 +/- 10 to 203 +/- 25 using dialyzers made of polysulfone. Plasma lactoferrin values were also significantly higher during hemodialysis with polyamide (772 +/- 110 micrograms/L) compared with hemophane (268 +/- 2.2) and the polysulfone (278 +/- 31 micrograms/L) dialyzer. After dialysis each dialyzer was rinsed. We found the lowest concentration of lactoferrin (902 +/- 254 micrograms/L) and E-alpha 1-PI (739 +/- 162 micrograms/L) after rinsing polysulfone dialyzers, whereas the highest concentrations were observed after rinsing the polyamide dialyzer (lactoferrin: 2,426 +/- 314; E-alpha 1-PI: 1,134 +/- 144 micrograms/L). Hemodialysis with polysulfone dialyzers caused significantly lower plasma levels of beta-2-microglobulin compared with polyamide or hemophane membranes despite significantly lower levels in the rinsing solutions. Our data indicate that low plasma levels of main granulocyte component observed with polysulfone and hemophane dialyzers are not the result of higher membrane adsorption of E-alpha 1-PI and lactoferrin. These main granulocyte components are not related to beta-2-microglobulin levels of both plasma and rinsing solutions.