On-line Regeneration Of Ultrafiltrate Research Articles

Isonatric Dialysis Biofeedback in Hemodiafiltration with Online Regeneration of Ultrafiltrate in Hypertensive Hemodialysis Patients: A Randomized Controlled Study

Dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR) could help to improve arterial hypertension. We evaluated the impact of isonatric HFR (HFR-iso) on hypertension control compared to conventional HFR. Forty-seven hemodialysis patients were included and randomized (ratio 2/1) HFR-iso versus HFR during 24 dialysis sessions. In the HFR-iso group (32 patients, 768 dialysis sessions), the predialytic systolic blood pressure (BP) decreased from S1 to S24 of 9 ± 20 mm Hg and increased of 5 ± 24 mm Hg in the HFR group (15 patients, 360 dialysis sessions), variation that differed between the 2 groups (ΔS1-S24, p = 0.035; interaction group*time, p = 0.012). The diastolic BP (HFR-iso -3 ± 14 mm Hg vs. HFR 5 ± 13 mm Hg; p = 0.088), the DDD of antihypertensive treatment and the dry weight did not vary significantly during the study. Number of sessions complicated by symptomatic hypotension was similar in the 2 groups. HFR-iso improved BP control without increasing dialysis hypotension episodes. Short Summary: In this multicenter, open-label, controlled, randomized study, we evaluated the impact of dialysis biofeedback in HFR on arterial hypertension compared to conventional HFR. We observed that HFR-iso improved arterial BP control without increasing dialysis hypotension episodes.

Hemodiafiltration with online regeneration of ultrafiltrate for severe nevirapine intoxication in a HIV-infected patient

Hemodiafiltration with online regeneration of ultrafiltrate for severe nevirapine intoxication in a HIV-infected patient

Isonatric dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR): rationale and study protocol for a randomized controlled study

Dialysate sodium prescription has major implications for hemodialysis tolerance but also for dialyzed patients' cardiovascular morbidity as a determinant factor of blood pressure. Biofeedback systems have been developed to drive dialysate conductivity in order to reach a prescribed serum sodium concentration, indirectly evaluated by a dialysate or an ultrafiltrate conductivity measurement. A biofeedback system using hemodiafiltration with online regeneration of ultrafiltrate (HFR) has been specially developed with an isonatric mode maintaining an equal serum sodium concentration between start and end of the dialysis session, combined with ultrafiltration and conductivity profiles. We hypothesized that using this biofeedback in an isonatric mode would have a beneficial effect on blood pressure and dialysis tolerance. The study protocol has been approved by our ethics committee and is presented herein.

The effects of 1-year treatment with a haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) dialysis on biomarkers of oxidative stress in patients with chronic renal failure

In the last few years haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) has been shown to have a positive impact on inflammation and oxidative stress biomarkers, but its effect on antioxidant levels and on oxidative damage to biomolecules in the long-term is still unknown. This is a randomised clinical study over 12 months involving 40 patients on haemodialysis, comparing the effect of HFR (n=25) dialysis with haemodialysis with polysulfone (HD-PS, n=15) on oxidative stress. Total antioxidant capacity, enzymatic antioxidant [superoxide dismutase (SOD), catalase and glutathione peroxidase], non-enzymatic (GSH) and biomarkers of oxidative stress (TBARs, carbonyl groups and 8-OH-dG) were evaluated. The antioxidant activity decreased in the lymphocytes of patients dialysed with HFR, with a significant decrease in the enzyme SOD. In the oxidative stress biomarkers, an increase was seen in the levels of 8-OH-dG in patients on HD-PS dialysis but not in those treated with HFR. Throughout the year the changes in antioxidant levels and biomarkers of oxidative damage in patients dialysed with HFR were generally more modest and fluctuated less than those dialysed with HD-PS. Our study indicates that, in general, long-term dialysis with HFR does not modified antioxidant parameters or increases the oxidative damage to biomolecules. The HFR showed to be a biocompatible technique for long-term dialysis.

Hemodiafiltration With Online Regeneration of Ultrafiltrate: Effect on Heme‐Oxygenase‐1 and Inducible Subunit of Nitric Oxide Synthase and Implication for Oxidative Stress and Inflammation

Hemodiafiltration with regeneration of ultrafiltrate (HFR) has a positive impact on inflammation and oxidative stress (OxSt), risk factors for cardiovascular disease (CVD), the most common cause of excess morbidity and mortality for end-stage renal disease (ESRD) patients. However, studies have been of limited duration. This study extends our previous study of HFR effects by evaluating the effect on mononuclear cell protein expression of heme-oxygenase-1 (HO-1), induced by OxSt, and inducible subunit of nitric oxide synthase (iNOS), and plasma level of interleukin-1β (Il-1β) and oxidized low-density lipoproteins (OxLDL), marker of OxSt, for a 12-month period. Fourteen ESRD patients stable on hemodialysis over a period of at least 2 years and on conventional bicarbonate dialysis were switched to be treated with HFR. Blood samples were collected at baseline, after 3, 6, 9 and 12 months. HO-1 and iNOS protein expression were evaluated by Western blot, OxLDL by enzyme-linked immunosorbent assay (ELISA), and Il-1β by enzyme amplified sensitivity immumoassay assay. HFR significantly increased HO-1 at the 9 and 12 months (ANOVA = P < 0.00001): 0.17 ± 0.11 (baseline) versus 0.48 ± 0.20, P < 0.043 and 0.59 ± 0.32, P < 0.004, respectively. Il-1β declined (ANOVA = P < 0.0001) since the 3 months from 169.92 ± 92.39 pg/mL (baseline) to 39.03 ± 10.01 (12 months), P < 0.0001. HFR also reduced plasma OxLDL: 475.4 ± 110.8 ng/mL (baseline) versus 393.1 ± 101.9 ng/mL (12 months), P < 0.04. iNOS showed no changes upon HFR treatment. These results together with our previous results indicate that HFR improves OxSt and inflammation. Given the strong relationships between OxSt and inflammation with CVD, their reduction might provide a beneficial impact by reducing the risk of atherosclerotic CVD in dialysis patients.

Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients

Increased oxidative stress (OxSt) as well as inflammation are risk factors for cardiovascular events and determinant of cardiovascular disease which remains the most common cause of excess morbidity and mortality for end-stage renal disease ESRD patients. Haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) has been shown to have a positive impact on markers of inflammation while its effect on OxSt is not known. This study evaluates in haemodialysis patients the effect of HFR on the plasma level of oxidized LDL (OxLDL), a marker of OxSt, and mononuclear cell gene and protein expression of OxSt-related proteins such as p22phox (subunit of NAD(P)H oxidase), PAI-1 (induced by OxSt and atherothrombogenetic) and haeme-oxygenase-1 (HO-1) (induced by OxSt). Fourteen patients were randomized into two groups in a crossover design, treated for 6 month periods with HFR (SG8 Plus-Bellco, Mirandola, Italy) or low-flux bicarbonate dialysis (HD) using a polysulphone dialyser 1.8 m2. Blood samples were collected at the beginning of the study, after 6 months (crossover) and after 12 months. ANOVA analysis of the data performed to rule out any crossover effect in either sequence was not significant and thus data from both sequences were combined and then analysed further statistically. HFR reduced mRNA production and protein expression of p22phox and PAI-1 compared with HD (-9+/-5 vs 2+/-6 Delta%, P<0.0001 and -15+/-20 vs 3+/-17 Delta%, P<0.05 for p22phox; -19+/-6 vs -5+/-5 Delta%, P<0.0001 and -24+/-12 vs 9+/-15 Delta%, P<0.0001 for PAI-1). HO-1 was unchanged (-12+/-8 vs -10+/-8 Delta% and -21+/-12 vs -14+/-8 Delta%) while plasma OxLDL was reduced (-14+/-19 vs 1+/-14 Delta%, P<0.01). The results of our study indicate that HFR treatment, compared with standard dialysis, has a lower impact on OxSt. Given, the strong relationship between OxSt and inflammation and their impact on the long-term cardiovascular complications in end-stage renal disease patients, HFR might have a more beneficial impact in reducing the risk of atherosclerotic cardiovascular disease in dialysis patients.

A Mathematical Model for the Prediction of Solute Kinetics, Osmolarity and Fluid Volume Changes during Hemodiafiltration with On-Line Regeneration of Ultrafiltrate (HFR)

Hemodiafiltration with on-line regeneration of ultrafiltrate (HFR) is a technique indicated for the treatment of dialysis patients affected by inflammatory syndrome and malnutrition. In the present work, a mathematical model, which describes intradialytic fluid and solute kinetics during standard diffusive dialysis, has been adapted to analyze solutes and fluid dynamics during HFR. The model is an improved version of our previous ones, and represents a good compromise between simplicity and reliability. It considers the intradialytic kinetics of sodium, potassium and urea, and two body fluid compartments: intracellular and extracellular. Moreover, the model includes simple equations to predict the intradialytic time pattern of osmolarity. The model has been experimentally validated by using 9 HFR sessions on 9 patients (one per each patient), comparing the time course of plasma solutes and osmolarity measured every 30 minutes during HFR, with those predicted by the model. Predictions are performed a priori, i.e., without any parameter adjustment, but just starting from knowledge of a few quantities (plasma sodium, potassium, urea, osmolarity and body weight) at the beginning of the session. The average deviations between model and real data (sodium: 1.9 mEq/L; potassium: 0.32 mEq/L; urea: 1.04 mmol/L; osmolarity: 5.02 mosm/L) are of the same order as measurement errors and similar to those obtained using our previous models in standard and profiled hemodialysis. Moreover, the prediction on sodium concentration only scarcely worsens (from 1.9 to 2.02 mEq/L) if default values are used for the initial value of other solutes in blood (i.e., if the algorithm uses only initial body weight and initial sodium concentration in plasma). The results confirm the good predictive capacity of the model in HFR, and suggest its possible innovative use to optimize sodium balance in HFR, from knowledge of only the sodium concentration in the ultrafiltrate.

In vivo Removal of High- and Low-Molecular-Weight Compounds in Hemodiafiltration with On-Line Regeneration of Ultrafiltrate

Background: Current methods of renal replacement therapy, combining convection and diffusion, are largely unsatisfactory in removing uremic toxins. Adsorption is a third mechanism that has been applied in extracorporeal therapy. This study evaluates the impact of hemodiafiltration with on-line regeneration of ultrafiltrate, a new two-step integrated sorbent system, on in vivo removal of a wide spectrum of solutes with different molecular weights. Methods: Pre- and post-dialysis concentrations of small, medium-size, and large molecules were determined in ten patients undergoing regular hemodiafiltration treatments with on-line regeneration of the ultrafiltrate. We also analyzed, at different times of the same dialysis session, the inlet and outlet ultrafiltrate; the latter had been regenerated by the sorbent cartridge and was used as reinfusion liquid. The mean dialysis time was 260 ± 21.2 min with a blood flow of 361 ± 33.3 ml/min and a reinjection volume of 3.6 ± 0.2 l/h. Results: Urea, creatinine and phosphate reduction ratio were respectively 69.8 ± 8.2, 61.9 ± 5.5, and 40.2 ± 17.3%. Removal of medium-size markers such as calcitonin, osteocalcin, β₂-microglobulin, cystatin C, myoglobin and prolactin varied between 24 and 60%. The percentage of reduction for retinol binding protein and α₁-microglobulin was negligible and we were unable to demonstrate any removal of α₁-acid glycoprotein, pre-albumin, and albumin in the regenerated ultrafiltrate. Conclusion: The hemodiafiltration with on-line regeneration of ultrafiltrate is a new hemodialysis system, which allows uremic toxin removal over a wide molecular-weight spectrum.

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

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. 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. 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). 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.