Vitamins (A, C and E) and oxidative status of hemodialysis patients treated with HFR and HFR-Supra.

BACKGROUND: Hemodiafiltration with on-line endogenous reinfusion (HFR) is an extracorporeal dialytic method that combines diffusion, convection and adsorption. HFR-Supra (HFR-S) is a second-generation system with increased convective permeability and adsorption capability. Previous studies suggested that HFR reduces oxidative stress compared to standard haemodialysis. The principal aim of the present study was to compare antioxidant vitamins behavior and oxidative status of hemodialysis patients treated with HFR and HFR-S. METHODS: The study was designed as a multicenter, randomized, crossover trial. Forty-one patients were recruited from 19 dialysis centers and after a 4-month washout stabilization period in on-line hemodiafiltration (ol-HDF), each patient was randomized to a sequence of treatments (HFR-S followed by HFR or viceversa) with each treatment applied over 6 months. Plasma levels of Advanced Oxidation Protein Products, Total Antioxidant Status, vitamins C, A and E and their ligands (Retinol Binding Protein and total lipids) were measured at baseline and at the end of each treatment period. RESULTS: Results show that the higher convective permeability of HFR-S with respect to HFR did not produce additional beneficial effects on the patients' oxidative status, a slight decrease of both Vitamin A and Retinol Binding Protein being the only difference registered in the long-term. However, as compared to ol-HDF, both the re-infusive techniques allowed to reduce the intradialytic loss of Vitamin C and, in the long-term, improve the patients' oxidative status and increase Retinol Binding Protein plasma values. No significant differences were found between the Vitamin C concentration of pre- and post cartridge UF neither in HFR-S nor in HFR showing that the sorbent resin does not adsorb Vitamin C. CONCLUSION: HFR-S and HFR are almost equivalent in term of impact on antioxidant vitamins and oxidative status of hemodialysis patients. Nonetheless, as compared to ol-HDF, both treatments produced a sensible sparing of Vitamin C and may represent a new approach for reducing oxidative stress and related complications in dialysis patients. Long-term effects of re-infusive treatments on patients' cardiovascular morbidity and mortality need to be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01492491 , retrospectively registered in 10 December 2011.

Effects of acetate-free haemodiafiltration (HDF) with endogenous reinfusion (HFR) on cardiac troponin levels.

BACKGROUND: Haemofiltrate reinfusion (HFR) is a form of haemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient 'regenerated' through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine haemodialysis and HDF contain small quantities of acetate (3-5 mMol/L) as stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. Cardiac troponin (cTnT) constitutes an appreciable marker of myocardial damage and cardiac hypertrophy, and correlates with left ventricular mass. METHODS: The aim of this study was to assess the impact of the presence or lack of acetate in DS on cTnT levels in patients treated with HFR and to evaluate outcome of intra-session cardiovascular stability. Twenty-five patients devoid of major cardiovascular comorbidity were randomized and treated with AF HFR for 3 months. The same patients were subsequently treated by means of HFR with DS containing 3 mMol/L acetate for 3 months and finally with AF HFR for a further 3 months. Prior and subsequent to each treatment period, samples were collected for cTnT measurement. RESULTS: A significant decrease was observed in cTnT levels throughout the first session of AF HFR (1.32 ± 0.35-1.12 ± 0.31 ng/mL, P < 0.05) with a subsequent rise being registered during HFR with acetate-containing DS (1.12 ± 0.31-1.28 ± 0.37 ng/mL, P < 0.05) and a further drop from 1.28 ± 0.37 to 1.21 ± 0.35 ng/mL in the last AF HFR period. During HFR with acetate-containing DS, a significant drop in systolic and diastolic arterial pressure was observed in conjunction with a higher heart rate at the end of the session. CONCLUSION: We observed an increase in cTnT during HFR with acetate and drops manifested during HFR without acetate; it may therefore be concluded that the drop in cTnT level, significantly correlated with lack of acetate, is indicative of improvement of cardiac microvascular function.

Hemodiafiltration with endogenous reinfusion.

Hemodiafiltration (HDF) is well known to increase the solute convective clearance due to increased ultrafiltration but requires substantial amounts of high-quality reinfusion fluid. Initially in the early 90s, individual bags or containers of reinfusion fluid were used and caused many problems related to handling (storage, repeated connections) and costs. Additionally there was an increased risk of circuit contamination. The interest in HDF pushed technological research for online production of sterile and ultrapure reinfusion solutions. Using a 2-chamber filter, it is possible to produce reinfusion fluid from the ultrafiltrate of the patient, which has been 'regenerated' by a sorbent bed, in a closed circuit. This action eliminates any problems of sterility and apyrogenicity, while also providing the possibility of reinfusing physiologically important substances such as bicarbonates and essential and branched-chain amino acids. This HDF method, called hemofiltrate reinfusion (HFR), has been clinically demonstrated to reduce the loss of physiological components and is associated with decreased inflammation and oxidative stress. In addition to its ease of use, the technique is also highly biocompatible. Based on these observations, HFR appears to be a useful technique for patients with complex risk factors such as malnutrition, inflammation and atherosclerosis.

Disinfection of dialysis monitors.

In recent years the concept of biocompatibility is not limited to the dialytic membranes, but has been substituted by a more general viewpoint where all the parameters of the dialytic treatment are taken into consideration: the interaction of blood-surfaces (the dialyzer in all its components and the hematic lines), the sterilization of all materials, the quality of the solutions utilized for dialysis and reinfusion. Numerous studies have shown that the inflammatory response in dialysis is the cause of many of the side effects of dialytic treatment itself both acute and chronic. Hypoxemia, 'first use' syndrome, hypotension, allergic-anaphylactic reactions (short-term side effects); microinflammation, malnutrition, accelerated arteriosclerosis, anemia, beta2 microglobulin amyloidosis, immunodeficiency, bone mass loss (long-term side effects), have all been reported. In this review, we will focus on the fluids utilized for hemodialysis (HD) and hemodiafiltration (HDF); we will describe the process of disinfection of the machines which produce the dialytic solutions.

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

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 microg/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.

One year of clinical experience in postdilution hemofiltration with online reinfusion of regenerated ultrafiltrate.

BACKGROUND/AIMS: Hemofiltrate reinfusion (HFR) is characterized by the use of regenerated ultrafiltrate as replacement fluid. We set up a new technique, postdilution HFR (PD-HFR), aiming at increasing purification efficiency, treatment tolerance and at reducing inflammatory states. METHODS: We performed PD-HFR in 6 uremic patients during 1 year. Dialysis efficacy, dialyzer blood loss and the behavior of cytokines were evaluated. RESULTS: No pyrogenic reactions or other adverse events were recorded. Treatment tolerance was excellent. We observed high urea extraction rates and optimal Kt/V values, high beta2-microglobulin (beta2m) extraction rates and a decrease in dialyzer blood loss; also IL-6 and TNF-alpha decreased significantly. CONCLUSIONS: Inversion of the standard HFR configuration has allowed us to improve the removal of both urea and beta2m, and to decrease dialyzer blood loss, with an optimal tolerance. Moreover, the decrease in cytokine levels might attenuate the uremic microinflammatory state.