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NDT Advance Access originally published online on November 22, 2005
Nephrology Dialysis Transplantation 2006 21(3):756-762; doi:10.1093/ndt/gfi189
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Articles: Dialysis and Transplantation

Effects on inflammatory and nutritional markers of haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over randomized multicentre trial

Vincenzo Panichi1, Giovanni Manca-Rizza1, Sabrina Paoletti1, Daniele Taccola1, Cristina Consani1, Cristina Filippi2, Emanuela Mantuano1, Antonino Sidoti3, Giovanni Grazi4, Alessandro Antonelli5, Daniela Angelini5, Isabella Petrone6, Carlo Mura7, Patricia Tolaini8, Franco Saloi9, Paolo M. Ghezzi1, Giuliano Barsotti1 and Roberto Palla10

1 Department of Internal Medicine, and 2 Neuroscience Department, University of Pisa, Pisa, 3 Renal Unit, Poggibonsi, 4 Renal Unit, Pontedera, 5 Renal Unit, Lucca, 6 Renal Unit, Pescia, 7 Renal Unit, Montevarchi, 8 Renal Unit, Castelnuovo Garfagnana, 9 Renal Unit, Barga and 10 Renal Unit, Massa, Italy

Correspondence and offprint requests to: Vincenzo Panichi MD, Dipartimento Medicina Interna, Via Roma 67, 56100 Pisa, Italy. Email: vpanichi{at}med.unipi.it



   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
 References
 
Background. HFR [double chamber haemodiafiltration (HDF) with reinfusion of regenerated ultrafiltrate] is a novel dialytic method which combines the processes of diffusion, convection and adsorbance. In this technique an adsorbent cartridge of resin and charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The aim of this multicentre randomized cross-over study was to compare HFR to online HDF in terms of inflammatory and nutritional parameters.

Methods. After a 1 month run-in period of standard bicarbonate dialysis (HD) with a synthetic membrane, 25 chronic dialytic patients were randomized (A-B or B-A) to be treated by HFR (A) with a two-chamber filter (SG 8 Plus – high permeability Polysulphone HF 0.7 m2 + SMC 1.95 sqm; Bellco, Mirandola, Italy) or by online sterile bicarbonate HDF. Each study period of 4 months was separated by 1 month of HD and the entire length of the study was 10 months. CRP levels were measured by a highly sensitive nephelometric assay (Dade, Behring) with a sensitivity of 0.1 µg/ml. Cytokine concentrations were determined by EIA [Interleukin (IL) 6, Biosource, USA and IL-10 Bender MED-Systems, Vienna]. The sensitivity thresholds were <5 pg/ml for IL-6 and <8 pg/ml for IL-10. Serum leptin was determined with a ELISA method (Biosource, USA). All parameters were determined monthly in patients starting a midweek dialytic session.

Results. Plasma CRP and IL-6 were significantly reduced during the 4 months of HFR and HDF: CRP from 8.0±3.2 to 5.6±3.4 mg/l with HFR (P<0.05) and from 9.4±4.3 to 5.9±3.9 mg/l with HDF (P<0.05). IL-6 decreased from 14.8±6.3 to 10.1±3.2 with HFR (P<0.02) and from 12.1±4.2 to 9.6±3.7 with HDF (P = ns) with a percentage decrease after 4 months of 32% with HFR vs 21% with HDF. During the 1 month wash-out period with HD, CRP increased from 5.7±3.6 to 8.7±3.9 mg/l (P<0.01) and IL-6 from 10±3.4 to 13.5±5.2 pg/ml (P<0.01). A significant increase in IL-10 was detected either in HFR (from 4.8±2.1 to 6.89±1.7 pg/ml) and in HDF (from 3.3±1.7 to 8.95±4.3 pg/ml; P<0.05) after 4 months. No significant variation in serum leptin levels were observed during the study. CRP and IL-6 were highly correlated (r = 0.54; P<0.001) as was serum albumin and prealbumin (r = 0.39; P<0.001). Serum albumin was negatively correlated with CRP (r = –0.26; P<0.01) and IL-6 (r = –0.19; P<0.05); serum prealbumin was correlated with IL-6 (r = 0.37; P<0.001) and with CRP (r = 0.24; P<0.01).

Conclusions. Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are highly biocompatible techniques and no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers. Further studies with a longer follow-up are needed to evaluate the clinical relevance of the online endogenous reinfusion to counteract the chronic inflammatory state of the uraemic patient.

Keywords: CRP; cytokines; dialysis; HFR; IL-6; IL-10; online haemodiafiltration



   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Conclusions
 References
 
Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor, which is commonly observed in dialysis patients, may cause malnutrition and progressive atherosclerotic cardiovascular disease by several pathogenetic mechanisms [1]. Available data suggest that pro-inflammatory cytokines play a central role in the genesis of both malnutrition and CVD in end-stage renal disease (ESRD). While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute phase reaction may also be a direct cause of acute vascular injury by several pathogenetic mechanisms. The cause(s) of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors [2,3]. Despite rapid improvements in dialysis technology during the last 20 years, the mortality rate in ESRD patients treated with dialysis is still unacceptably high; therefore studies on the effects of various anti-inflammatory treatment strategies, either pharmacological or dialytic, on the nutritional and cardiovascular status as well as outcome in this patient group are warranted [4]. HFR (double chamber HDF with reinfusion of ultrafiltrate regenerated through a charcoal–resin cartridge) is a novel method which combines the processes of diffusion, convection and adsorbance [5]. During HFR, the ultrafiltrate derived by the convective section of the filter is processed by a charcoal–resin cartridge and the regenerated ultra-filtrate is reinfused into the bloodstream before the diffusive section of the filter.

Several studies suggest that bacterial contamination of dialysate may enhance cytokine production in haemodialysis; therefore back-filtration of bacterial contaminated dialysate may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding back-filtration of contaminated dialysate [6]. HFR is a peculiar technique in which the second chamber is made of a low-permeability membrane to ensure diffusion and the patient's weight loss. This low-permeability diffusive membrane in the second stage of the HFR filter reduces the risk of back-filtration of dialysate so that it is similar to that of a typical low-flux HD, and less than that using high-permeability membranes in high-flux haemodialysis and HDF. Furthermore, the resin component of the cartridge is able to adsorb several medium–high-molecular weight solutes and in particular pro-inflammatory cytokines [7].

The main working hypothesis of this study is based on the assumption that online HFR could reduce or eliminate the chronic inflammatory state and therefore improve nutritional parameters. The aim of this multicentre randomized cross-over study was to compare haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration in terms of inflammatory and nutritional parameters.



   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Conclusions
 References
 
Patients
Twenty-five chronic, clinically stable uraemic patients in regular dialytic treatment for at least 1 year prior to the study (M/F 1.5:1; mean age of 67.5±13.8 years and mean dialytic age 81±36 months) were included in a multicentre randomized study. Chronic renal failure was caused by chronic glomerulonephritis in 16 patients, adult polycystic kidney disease in four patients, chronic pyelonephritis in three patients and renal failure of uncertain etiology in the remainder. Twenty-one patients had an arteriovenous fistula and four a subcutaneous polytetrafluoroethylene graft (PTFE).

This study lasted 10 months and was conducted in nine haemodialysis centres from November 2003 to December 2004. Informed consent was requested and given in written form. Patients with conditions that could influence cytokine production such as acute infection or blood transfusion in the past month, chronic infection, active immunological disease, immunosuppressive therapy, previous transplantation or history of malignancy were excluded from the study. During the study periods, patients were carefully checked for co-morbidities and infections, in particular regarding dialysis access.

Study design
After a 1 month run-in period of standard bicarbonate dialysis (HD) patients were centrally randomized into two groups according to the type of treatment (Figure 1). Group I: 13 patients (56±13 years; 8M and 5F) were treated for 4 months with HFR; after 1 month of HD they were transferred to HDF for 4 months. Group II: 12 patients (mean age 63±11 years; 7M and 5F) were treated for 4 months with HDF, after 1 month of HD they were transferred to HFR for 4 months.


Figure 1
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  		Fig. 1. Study design. After a 1 month run-in period of standard bicarbonate dialysis (HD), patients were centrally randomized into two groups according to the type of treatment. Patients treated for 4 months with HFR, after 1 month of HD, were transferred to HDF for 4 months. Patients treated for 4 months with HDF, after 1 month of HD, were transferred to HFR for 4 months.

 
Dialytic modalities
HFR: A double-chamber haemodialyser consisting of a 0.7 m2 high permeability Polysulphone membrane as a convective dialyser and a 1.95 m2 SMC membrane in diffusive dialyser (SG 8 Plus Bellco, Mirandola, Italy) was used. The two chambers of the filters are arranged in series. The ultrafiltrate obtained by the convective section of the filter is processed by a charcoal–resin cartridge; the regenerated ultrafiltrate is re-infused into the bloodstream before the diffusive section of the filter. The regenerating adsorbent cartridge (Selecta Plus, Bellco) used contains two adsorbent materials: white spherical particles of undissolvable macro-porous-structured styrenic resin (20 ml) and activated uncoated charcoal (240 ml). On the non-ionic macroporous resin are adsorbed medium–high-molecular weight solutes as pro-inflammtory cytokines, beta-2 MG and AGEs, and charcoal is able to adsorb creatinine and uric acid and several other low-molecular weight solutes. After passage through the charcoal cartridge, the ultrafiltrate was reinfused between the two dialysers in series. Blood flow was 330±20 ml/min and dialysate flow was 545±85 ml/min.

Bicarbonate dialysate was purified by sterile filtration before entering the dialyser. The Quf from the convective sector and the reinfusion were kept at 50–60 ml/min. The weight loss, all obtained from the diffusive sector was 1000±60 g/h with a dialytic time of 240±15 min. The compositions of the dialysate were Na 139 mmol/l, K 1.5 mmol/l, HCO3 39 mmol/l and Ca 1.5 mmol/l. Immediately before use the double-chamber filters' haemodialyser and cartridge were washed with 2 litres of saline solution to eliminate the storage solutions. The charcoal cartridge was used only once.

HDF: Postdiluition haemodiafiltration was performed using a specifically designed system incorporating an online preparation of substitution solution. The dialysate is prepared by proportioning ultrafiltered water, derived by passing it through a single-use ultrafilter, liquid acid concentrate and liquid bicarbonate concentrate made on-line from a dry powdered cartridge. This substitution solution is then rendered ultrapure by passage through a second ultrafilter. The present study used high-flux polyamide (1.7 m2) and high-flux polysulphone membranes (1.8–2.0 m2). The blood flow was 330±20 ml/min with a dialysate flow of 570±85 ml/min. The ultrafiltration rate was 4500±250 ml/h with a weight loss of 910±100 g/h in dialytic time of 240±15 min.

HD: Standard bicarbonate dialysis was performed with low-flux synthetic highly biocompatible membranes (polysulphone and polyamide) with a surface area ranging from 1.6 to 1.9 m2, with a blood flow of 320±41 and a dialysate flow of 550±100 ml/min, dialytic time 240±15 min and a weight loss of 840±90 g/h. The composition of the dialysate was Na 139 mmol/l, K 1.5 mmol/l, HCO3 39 mmol/l, and Ca 1.5 mmol/l. Patients were weighed before and after each treatment, to determine the volume of ultrafiltration. Net fluid removal was set on an individual basis according to the patient's clinical need. All haemodialysis treatments were carried out with a volumetric control machine allowing for a precise rate of fluid removal.

Biochemistry
Predialysis serum urea, creatinine, albumin, beta-2microglobulin, total calcium, phosphate and bicarbonate were measured at the start of the study and at monthly intervals. Haemoglobin, white cell, lymphocyte and platelet counts were also assessed monthly. Urea kinetics were performed monthly in a mid-week session according to the methods of Gotch and Sargent [8]. Postdialysis urea samples were obtained 10 min after the end of the dialysis session.

Inflammation and nutritional parameters
All parameters were determined monthly in patients starting a mid-week dialytic session. CRP was measured by a high sensitivity modified laser nephelometry technique (Berhing Diagnostics, Gmbh, Rarburg). The CRP assay was standardized according to the WHO First International Reference Standard and had a sensitivity of 0.1 µg/ml, with a standard reference range of between 0.1–0.4 mg/l. IL-6 (Biosource, USA) and IL-10 (Bender, USA) were measured by quantitative sandwich enzyme immunoassay techniques. Plasma, collected using heparin as anti-coagulant, was separated less than 30 min after drawing and stored at –40° until analysis. Samples were assayed in duplicate and the intra and inter-assay coefficient of variation for IL-6 was less than 5.3 and 7.2%, respectively. The limit detection of IL-6 was less than 5 pg/ml. Serum pre-albumin and albumin were measured with a nephelometric technique (Dade Behring Marburg GmbH) with an intra and interassay variability of 4.3 and 4.4%, respectively. Leptin was determined using enzyme-linked immunoassays (ELISA; Linco Research, St Charles, MO, United States).

Sensitivity was 0.5 ng/ml with an intra- and inter-assay variation of less than 5% and less than 10%, respectively.

Clinical tolerance
Complications during the dialytic sessions such as hypotension, cramps, headache, arrythmias, hypertension and angina were recorded. Extradialytic symptoms such as thirst, pruritus, weakness, cramps, dyspnoea and vomiting were also recorded.

Statistics
Results were expressed as mean±SE. The difference between the mean values in the two groups was evaluated by Student's t-test; analysis of variance (ANOVA test) for multiple comparisons was used to analyse differences between the three different dialytic modalities. Correlation between two variables was examined by simple regression analysis. A P-value less than 0.05 was taken to be statistically significant.



   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Conclusions
 References
 
Inflammatory markers
Plasma CRP and IL-6 were significantly reduced during the 4 months of HFR and HDF: CRP from 8.0±3.2 to 5.6±3.4 mg/l with HFR (P<0.05) and from 9.4±4.3 to 5.9±3.9 mg/l with HDF (P<0.05). IL-6 decreased from 14.8±6.3 to 10.1±3.2 with HFR (P<0.02) and from 12.1±4.2 to 9.6±3.7 with HDF (P = n.s.) with a percentage decrease after 4 months of 32% in HFR vs 21% with HDF.

During the 1 month wash-out period on HD, CRP increased from 5.7±3.6 to 8.7±3.9 mg/l (P<0.01) and IL-6 from 10±3.4 to 13.5±5.2 pg/ml (P<0.01). The detailed data are reported in Figures 2 and 3. CRP and IL-6 were highly related (r = 0.53; P<0.001) as shown in Figure 4. The effect of the dialytic modalities (BD, HDF, HFR) on inflammatory markers were assessed by univariate analysis of variance (ANOVA) and in Table 1 we have reported the differences that were statistically significant; no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers.


Figure 2
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  		Fig. 2. Variations in serum CRP level during the study. Plasma CRP was significantly reduced after 1 and 4 months of HFR (P<0.04) in comparison to the HD month. Furthermore, CRP significantly increased (P<0.03) when patients were transferred from HFR4 to HD. Finally, CRP was significantly reduced after 4 months of HDF (P<0.05). As shown in Figure 1, after 1 month of bicarbonate dialysis (HD) patients were randomized to start either HFR or HDF. In this figure the cumulative results for each technique are depicted.

 

Figure 3
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  		Fig. 3. Variations in serum IL-6 level during the study. Plasma IL-6 was significantly reduced after 4 months of HFR (P<0.04) in comparison to the HD month. Furthermore, IL-6 significantly increased (P<0.04) when patients were transferred from HFR4 to HD. Finally, no significant reduction of IL-6 was observed during the 4 months of HDF (NS). As shown in Figure 1, after 1 month of bicarbonate dialysis (HD) patients were randomized to start either HFR or HDF. In this figure the cumulative results for each technique are depicted.

 

Figure 4
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  		Fig. 4. Correlation between serum CRP level and IL-6 level. CRP and IL-6 were highly related (r = 0.53; P<0.001).

 

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  		Table 1. The effect of the dialytic modalities on inflammatory markers including CRP and IL-6. One-way analysis of variance (ANOVA). Post hoc test at P<0.05. Dialytic treatment effect on inflammatory markers CRP and IL-6: HD1 vs HFR4, HFR4 vs HD2, HD2 vs HDF4

 
A significant increase in IL-10 was detected in HFR (from 4.8±2.1 to 6.89±1.7 pg/ml) and in HDF (from 3.3±1.7 to 8.95±4.3 pg/ml; P<0.05) after 4 months: In HD plasma, IL-10 levels decreased from 6.8±1.7 to 4.2±1.8 pg/ml.

Nutritional markers
No significant variation in serum leptin levels were observed during the study. Plasma leptin remained unchanged in HFR (from 9.17±2.1 to 9.71±3.1 ng/ml; P = ns), during the HD wash-out month (from 9.71±3.1 to 8.6±2.7 ng/ml; P = ns) and in HDF (from 8.6±2.3 to 8.14±2.5 ng/ml; P = ns) Serum albumin and prealbumin were highly correlated (r = 0.39; P<0.001). A slight but not significant increase in serum albumin was observed during HFR and HDF periods (from 3.5±0.23 to 3.83±0.25 g/dl in HFR, and from 3.59±0.22 to 3.73±0.20 g/dl in HDF).

Nutritional markers were inversely correlated with inflammatory markers including CRP and IL-6.

Serum albumin was negatively correlated with CRP (r = –0.26; P<0.01) and IL-6 (r = –0.19; P<0.05); serum prealbumin was more strongly inversely correlated with IL-6 (r = –0.37; P<0.001) than with CRP; (r = –0.24; P<0.01).

Biochemical markers
A non-significant reduction in beta-2microglobulin was observed in the HFR (Table 2); no significant differences in serum albumin and prealbumin were observed during the study (Table 2). Mean dry weight remained constant during the whole duration of the study.


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  		Table 2. The effect of the dialytic modalities on nutritional markers and beta-2microglobulin during the study

 
Clinical tolerance
Dialysis-related symptoms and dialysis-associated hypotension were not significantly different in the different haemodiafiltration modalities. No particular complaints were noted in patients either during or between sessions; subjective assessment was positive for all patients and no changes were observed in medication throughout the study. No pyrogenic reactions were observed throughout the study.

Patients, body temperature did not show significant inter-individual differences.



   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Conclusions
 References
 
In this study, the assessment of the acute phase response induction shows that HFR is comparable with ultrapure online HDF in terms of IL-6 and CRP production. Moreover, a significant reduction of IL-6 on dialysis plasma levels was detected in HFR after 4 months (32% in HFR vs 21% in HDF). This finding is very interesting, because recent studies have showed that IL-6, rather than CRP, better predicts cardiovascular mortality in haemodialysis patients [9].

Haemodiafiltration with online regeneration of ultrafiltrate (HFR) is a highly biocompatible technique, combining the delivery of ultrapure dialysate to the adsorption of pro-inflammatory factors by the resin. Cole et al. [10] with an elegant experimental study showed that it is possible to remove, simultaneously, a range of preformed pro-inflammatory cytokines from an extracorporeal circuit with coupled haemofiltration and adsorption, using a haemofilter with a nominal average 150 kDa pore size and an uncoated charcoal cartridge.

Furthermore, the reinfusion of a sterile and pyrogen-free fluid could have an impact on the overall biocompatibility of the dialysis system and possibly on reducing cytokine generation. Several studies have reported beneficial effects of changing from conventional to ultrapure dialysis fluid. In a randomized study, Sitter et al. [11] assigned 15 patients to a group treated with conventional (with potential microbiologic contamination) dialysate and 15 patients to a group treated with online produced ultrapure dialysate. A significant, sustained reduction of the erythropoietin dose, accompanied by a decrease in C-reactive protein and IL-6 levels, was observed in the ultrapure dialysate group.

Masakane et al. [12] reported in 55 patients that ultrapure dialysate has beneficial effects on haematocrit and serum albumin. However, in a pilot study on eight chronic dialytic patients, the change from bicarbonate haemodialysis to HFR was safe and well tolerated, but was not associated with an improvement of nutritional and inflammatory parameters or a reduction of serum beta-2microglobulin levels [13]. Interestingly, after a switch to HFR, CRP levels tended to be lower at the end of the study than at baseline, although the difference was not statistically significant for the small number of patients in this study.

Furthermore, HFR and online HDF resulted in a significant improvement in inflammatory parameters in comparison to bicarbonate haemodialysis. Apart from the role of cytokines in convective removal or adsorption, several in vitro and in vivo experiments suggested that pyrogen permeability of dialyser membranes are influenced by the characteristics of the dialyser membrane, such as the capability of the membrane polymer to adsorb CIS, membrane thickness and the formation of a second protein layer of plasma proteins on the dialyser surface [14].

In this study we have also investigated the variations of IL-10, an anti-inflammatory cytokine, that may influence the effects of a broad range of pro-inflammatory factors [15]. Chronic uraemic patients are characterized by a low-grade systemic inflammation that reflects the consequences of an unbalanced production of pro-inflammatory and anti-inflammatory cytokines and contributes to the progression of atherosclerotic vascular disease and malnutrition. IL-10 is known to counter-regulate the cascade of pro-inflammatory cytokines, including IL-6, as part of the acute-phase reaction. The importance of IL-10 as an anti-inflammatory cytokine is emphasized by a recent study in which a low-producing IL-10 gene polymorphism was associated with a higher cardiovascular morbidity and mortality in a cohort of haemodialysis patients [15]. In this study, we suggest that ultrapure and highly biocompatible dialysis techniques with increased IL-10 production may counteract the chronic inflammatory state of uraemia by a feedback inhibition of pro-inflammatory cytokine production.

Elevated levels of pro-inflammatory may be an important cause of wasting syndrome in dialysis patients [16]. The effects of cytokines may result from their catabolic effects on protein metabolism or their direct action on the gastrointestinal system or indirect effects mediated by cytokines in the central nervous system, resulting in anorexia [17]. The mechanism by which elevated serum levels of pro-inflammatory cytokines cause anorexia are not clear. However, inflammation has been speculated to mediate anorexia through the anorexic hormone leptin which, at least in animal experiments, has been shown to be up-regulated by pro-inflammatory cytokines [18]. Leptin is a hormone secreted by adipocytes, which regulates food intake, thermogenesis and body fat. Plasma leptin has been described as significantly elevated in haemodialysis patients over the general population and our data confirm these elevated values [19].

Finally, although this study confirms that serum albumin and prealbumin are directly correlated and inversely related to inflammatory markers, no significant variation was observed during the study in the visceral protein pool. Serum albumin levels increased in both online haemodiafiltration and HFR during the 4 month study period with respect to conventional haemodialysis, but did not reach statistical significance.

Schiffl et al. [20] randomly assigned 48 patients to conventional or ultrapure dialysate; changing from conventional to ultrapure dialysis fluid significantly reduced IL-6 and C-reactive protein levels and resulted in significant increases in estimated dry body weight, serum albumin concentration and protein catabolic rate after 12 months. We believe that the shorter follow-up of our study and the smaller population observed may explain the lack of significance of nutritional parameters in this study.



   Conclusions
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
References
 
Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are highly biocompatible techniques and no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers.

These preliminary data, which need confirmation in a long-term study, seem to indicate that HFR is a highly biocompatible technique able to reduce the chronic inflammatory response that by several pathogenetic mechanisms may cause malnutrition and progressive atherosclerosis. Further studies with a longer follow-up are needed to evaluate the clinical relevance of the online endogenous re-infusion in counteracting the chronic inflammatory state of the uraemic patient.



   Acknowledgments
 
This work was partially supported by a grant from Bellco, Mirandola-Italy.

Conflict of interest statment. None of the Authors declared involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. Prof. PM Ghezzi is an external consultant for Bellco, Mirandola-Italy.



   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
 References
 

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Received for publication: 17. 2.05
Accepted in revised form: 9. 9.05


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L. A Calo, A. Naso, G. Carraro, M. L. Wratten, E. Pagnin, L. Bertipaglia, M. Rebeschini, P. A Davis, A. Piccoli, and C. Cascone
Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients
Nephrol. Dial. Transplant., May 1, 2007; 22(5): 1413 - 1419.
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