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The low bath bicarbonate concentration ([ HCO 3 - ]) used by a nephrology group in Japan (25.5 mEq/L), coupled with a bath [acetate] of 8 mEq/L, provided an opportunity to study the acid-base events occurring during hemodialysis when HCO 3 - flux is from the patient to the bath. We used an analytic tool that allows calculation of HCO 3 - delivery during hemodialysis and the physiological response to it in 17 Japanese outpatients with an average pre-dialysis blood [ HCO 3 - ] of 25 mEq/L. Our analysis demonstrates that HCO 3 - addition is markedly reduced and that all of it comes from acetate metabolism. The HCO 3 - added to the extracellular fluid during treatment (19.5 mEq) was completely consumed by H+ mobilization from body buffers. In contrast to patients dialyzing with higher bath [ HCO 3 - ] values in the US and Europe, organic acid production was suppressed rather than stimulated. Dietary analysis indicates that these patients are in acid balance due to the alkaline nature of their diet. In a larger group of patients using the same bath solution, pre-dialysis blood [ HCO 3 - ] was lower, 22.2 mEq/L, but still in an acceptable range. Our studies indicate that a low bath [ HCO 3 - ] is well tolerated and can prevent stimulation of organic acid production.

Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p

A novel in vitro test (T50 test) assesses ex vivo serum calcification propensity and predicts mortality in chronic kidney disease and haemodialysis (HD) patients. For the latter, a time-dependent decline of T50 was shown to relate to mortality. Here we assessed whether a 3-month switch to acetate-free, citrate-acidified, standard bicarbonate HD (CiaHD) sustainably improves calcification propensity.T50 values were assessed in paired midweek pre-dialysis sera collected before and 3 months after CiaHD in 78 prevalent European HD patients. In all, 44 were then switched back to acetate. Partial correlation was used to study associations of changing T50 and changing covariates. Linear mixed effect models were built to assess the association of CiaHD and covariates with changing T50.A significant intra-individual increase of serum calcification resilience was found after 3 months on CiaHD (206 ± 56 to 242 ± 56 min; P 0.001), but not after switching back to acetate (252 ± 63 to 243 ± 64 min; n = 44; P = 0.29). CiaHD, Δ serum phosphate and Δ albumin but not Δ ionized calcium and magnesium were the strongest determinants of changing T50. Beneath T50, only serum albumin but not phosphate changed significantly during 3 months of CiaHD.CiaHD dialysis favourably affected calcification propensity as measured by the T50 test. Whether this treatment, beyond established phosphate-directed treatments, has the potential to sustainably tip the balance towards a more anti-calcific serum milieu needs to be further investigated.

Background: Extracorporeal carbon dioxide removal may be used to manage hypercapnia, but compared to dialysis, it’s not widely available. A recent in vitro study showed that dialysis with low bicarbonate dialysates removes CO2. Objective: To show that bicarbonate dialysis removes CO2 in an animal model to validate in-vitro findings and quantify the effect on arterial pH. Methods: Male Sprague-Dawley hypercapnic rats were dialyzed with either a conventional dialysate (PrismasolTM) or a bicarbonate-free dialysate (Bicarb0). The effect of dialysis on standard blood gases and electrolytes was measured. Results: Partial pressure of CO2 and bicarbonate concentration in blood decreased significantly after exposure to Bicarb0 compared to PrismasolTM (filter outflow values 12.8 vs 81.1 mmHg; p 2 and 3.5 vs 22.0 mmol/L; p 2 content of blood was reduced by 459 mL/L during dialysis with Bicarb0 (filter inflow 546 ± 91 vs filter outflow 87 ± 52 mL/L; p TM. Conclusions: Bicarbonate dialysis removes CO2 at rates comparable to existing low-flow ECCO2R.

“Acetate intolerance” was one of the first negative signs of acetate hemodialysis registered in the history of the treatment of chronic renal failure. Now we consider an error such an approach to kidney disease. But it was an “institutional” error according to the classification of the Italian historian of Medicine, Ettore De Benedetti, to distinguish it from the “personal” error, committed after the revision of acetate treatment and the introduction of bicarbonate dialysis. The same difference could be considered in the “short hemodialysis” technique for the adverse cardiovascular outcome. Many examples of “institutional” and “personal” errors in nephrology are reported. Errors need to be recorded and to be analysed if we want to discover why they occur and how they must be prevented. If we want to eliminate errors, it is mandatory to overcome certain attitudes, deeply rooted in the profession. Medical attitudes are often determined by medical bioethics and by the principles that determine whether ideas or actions are considered right or wrong. Errors by doctors are common. In order to reduce errors many authorities tried to reduce them giving some methodological advices. Very important are the proposals of a clinician, Neil McIntyre, and a philosopher, Karl Popper, for a “new” professional ethics summarized in ten theses, reported in this article. (Bioethics)

Background: Short frequent dialysis with NxStage System One cycler (NSO) has become increasingly popular as home hemodialysis prescription. Short dialysis sessions with NSO might not allow adequate phosphate (P) removal. Methods: Single-session and weekly balances of P and calcium (Ca) were compared in 14 patients treated with NSO (6 sessions/week) and in 14 patients on standard bicarbonate dialysis (BHD). Results: NSO and BHD showed similar plasma P fall, with end-dialysis plasma P slightly lower in BHD (2.2 ± 0.5 vs. 2.7 ± 0.8 mg/dL, p < 0.02). Single-session P removal was lower in NSO, but weekly removal was higher (3,488 ± 1,181 mg vs. 2,634 ± 878, p < 0.003). Plasma Ca increase was lower in NSO, with similar PTH fall. Ca balance varied according to start plasma Ca, dialysate to blood Ca gradient and net ultrafiltration. Conclusions: short, frequent home hemodialysis with NSO, on a 6/week-based prescription, allows higher weekly P removal than BHD. With the dialysate Ca concentration in use (6 mg/dL), total plasma Ca and iCa concentration increase is lower in NSO.

Little information have been provided till now regarding the effect of high volume HDF (hv-OL-HDF) in respect to standard bicarbonate dialysis (BHD) in medium-long term protein-bound toxins removal. A randomised cross-over multicentre study (REDERT study) was designed to compare the effects of hv-OL-HDF and low-flux BHD on uremic toxins serum levels in 36 chronic dialysis patients followed for 13 months. Group 1 patients were treated with BHD (Treatment A) for 6 months, and afterwards, they were transferred to hv-OL-HDF for a further 6 months (Treatment B). Group 2 patients were treated with Treatment B for 6 months, and afterwards, they were transferred to Treatment A for a further 6 months. Total and free pre-dialysis indoxyl-sulfate (IS) and p-cresyl-sulfate (pCS) were determined starting a midweek dialysis session at baseline and after six months of hv-OL-HDF or BHD. IS and pCS, were simultaneously measured, by liquid chromatography/electrospray ionization-tandem mass spectrometry, Kt/v and pre and post-dialysis b-2microglobulin (b2MG) levels were measured every three months. Kt/V was significantly increased in hv-OL-HDF (from 1.47 ± 0.24 to 1.49 ± 0.16; p

This study was aimed to evaluate the effects on some inflammatory markers of two dialytic treatments [bicarbonate dialysis (BHD) and hemodiafiltration (HDF)] in patients with severe chronic kidney disease. We evaluated: blood glucose, homeostasis model assessment insulin resistance index, homocistein (Hcs), high sensitivity C-reactive protein (hs-CRP), fibrinogen, lipoprotein (a) [Lp(a)], metalloproteinases-2, and -9 (MMP-2 and MMP-9), and soluble receptor for advanced glycation end products (sRAGE). Considering the all sample, we observed a decrease of sRAGE with BHD, but not with HDF. Fibrinogen, MMP-2, and -9, Hs-CRP decreased after HDF, but not after BHD. In diabetics, blood glucose decreased after HDF dialysis, but not after BHD. Soluble receptor for advanced glycation end products obtained with HDF were higher compared to BHD. Fibrinogen, MMP-2, MMP-9, Hcs, Hs-CRP decreased, and ADN increased after HDF, these changes did not happen after BHD. Furthermore, sRAGE, and ADN were higher, and MMP-2 lower after HDF. In euglycemic patients, instead, MMP-2, MMP-9, and Hs-CRP decreased, and ADN increased with HDF, but not with BHD. We can conclude that hemodiafiltration seems to greater reduce inflammatory markers, and it could be more suitable for people with type 2 diabetes. Registration number: ClinicalTrials.gov NCT01049152.

Most End-Stage Renal Disease (ESRD) patients receiving dialysis therapy are in a state of constant metabolic acidosis which is associated with high cardiovascular morbidity and mortality. In an attempt to improve the quality and efficacy of ESRD patients suffering from acidosis many experimental approaches have been used to investigate acid–base balance during dialysis sessions. However, these experimental approaches are expensive and time consuming. To reduce acidosis morbidity, a compartmental mathematical model is used in this paper. The model takes into account the exchange of small solutes, bicarbonate (HCO3−) and carbon dioxide, across a non-uniform trans-membrane dialyzer. Blood and dialysate flows are simulated using the Navier–Stokes and Darcy equations respectively. Since the trans-membrane (TM) flux would not be uniform, both blood- and dialysate-side equations are coupled with interfacial conditions calculated by Kedem–Katchalsky equations. Numerical results and clinical data are in close agreement within a satisfactory range, thus confirming that mathematical models can predict dialysis operative parameters with accuracy. Numerical results also confirm that acid–base balance for ESRD patients can be achieved during HCO3− dialysis therapy. Thus, the model quantifies adequate choice of bicarbonate and electrolyte concentrations to help improve acid–base status of ESRD patients suffering from acidosis. As an investigative framework, the model can also provide a clear insight into other small solute exchanges across the dialyzer membrane.

The use of bicarbonate-based dialysis fluids in hemodialysis centers in the United States has increased with the advent of high-efficiency and high-flux hemodialysis. However, bicarbonate dialysis fluids can support rapid bacterial growth and high endotoxin concentrations. This study determined the efficacy of an ultrafiltration device in reducing the bacterial and endotoxin concentrations in bicarbonate dialysis fluids. A polysulfone hollow fiber dialyzer was used to ultrafilter bicarbonate concentrate before entering the central proportioner and bicarbonate dialysate after exiting the proportioner in single patient dialysis machines. Pre- and post-ultrafilter samples were collected for bacterial and endotoxin assays over 10 months. Ultrafiltration of bicarbonate concentrate reduced bacterial and endotoxin concentrations from 288,330 colony forming units (CFU)/ml and 42,804 pg/ml too.47CFU/mland 109 pg/ml, respectively. Ultrafiltration of the dialysate in single patient systems decreased bacterial and endotoxin concentrations from 15,889 CFU/ml and 1,746 pg/ml to 0.003 CFU/ml and 0.109 pg/ml, respectively. These results demonstrate that ultrafiltration of bicarbonate dialysis fluids is effective in reducing bacterial and endotoxin contamination inherently associated with the use of bicarbonate-based dialysates.

Background. In patients on on-line convective treatments, given the considerable quantity of dialysis fluid re-infused, the small amount of acetate present in bicarbonate dialysis fluid as a pH stabilizing factor may allow a significant transfer of that anion to the patient, possibly inducing cytokine activation. Methods. To verify this hypothesis, we performed on-line haemodiafiltration (OL-HDF) with (3 mmol/l) and without acetate in dialysis fluid in a cross-over randomized order on 12 prevalent patients. Results. In comparison with the pre-treatment values, plasma acetate levels were unchanged during and after acetate-free OL-HDF, while they were 5–6 times higher in the course of OL-HDF containing acetate in dialysis fluid; plasma acetate levels returned to basal values 2 h after the end of the procedure. The total increase of bases in the patient attributable to acetate was 36%. Plasma bicarbonate values at the end of treatment were significantly lower in treatments without acetate, as compared to those with acetate. Interleukin-6 plasma levels were super-imposable at the beginning and in the course of the two methods compared, but there was a tendency towards a greater increase at an interval of 2 h following OL-HDF with acetate. Conclusions. Our preliminary results confirm the assumption that body gain of acetate is particularly high in convective treatments, while acetate-free OL-HDF slows down acetate burden. Clinical advantages due to these effects should be evaluated in properly designed prospective studies.

This study aimed at evaluating the feasibility of an acetate-free hemodialysis (AFHD) technique, comparing it with acetate-free biofiltration (AFB) and bicarbonate dialysis (BD). The assessment of the parameters concerned: electrolyte kinetics (Na+, K+), acid-base balance (HCO3–, pH), dialysis efficiency (Kt/V), serum β2-microglobulin reduction ratio, nutritional status (normalized protein catabolic rate, serum albumin and total proteins, body mass index), hemopoietic status (hemoglobin, hematocrit), and some clinical parameters (systolic and diastolic blood pressures, heart rate, percent blood volume reduction measured by Hemoscan®). Nine patients participated in this study which was conducted using a Latin square randomized experimental design. The results of the last week of each month of the study (1 month for each technique) were analyzed by means of Anova for repeated measures. The different treatments were comparable with regard to the main dialysis parameters such as blood flow (320 ml/min) and weight loss rate (0.6 ± 0.1 kg/h), while dialysis length and dialysate conductivities were different, depending on the dialysis technique. Electrolyte kinetics and acid-base balance were similar during the three periods. The dialysis efficiency for small molecules (Kt/V of urea) was similar (between 1.4 and 1.6); however, AFB seemed to show a higher β2-microglobulin reduction rate (47.6 ± 4 vs. 4.3 ± 10% for AFHD and vs. 9.9 ± 5% for BD; p < 0.001). The nutritional and hemopoietic status maintained stable, and the hemodynamic parameters were comparable during all periods. The percent blood volume reduction at the end of the treatments was not statistically different (–14.9 ± 9.4% in AFB, –12.1 ± 5.1% in AFHD, and –12.2 ± 4.4% in BD), and these results could explain the similar hemodynamic behavior during the three periods. In conclusion, AFHD appears to be a safe technique which has all positive effects of AFB and the low costs of BD. In our opinion, it could be used in patients with few clinical impairments, usually treated with hemodialysis, in whom a biocompatible treatment is indicated.

Recent work has shown that the dialyzer mass transfer area coefficient (Ko A) for urea increases when the dialysate flow rate is increased from 500 to 800 mL/min. In this study we determined urea and creatinine clearances for two commercial dialyzers containing polysulfone hollow fibers in vitro at 37°C, a nominal blood flow rate of 300 mL/ min, and dialysate flow rates (Qd ) ranging from 100 to 800 mL/min. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from solute concentrations in the input and output flows on both the blood and dialysate sides. Urea and creatinine Ko A values, calculated from the mean of the blood and dialysate side clearances, increased (p < 0.01) with increasing Qd over the entire range studied. The increase in both urea and creatinine Ko A with increasing Qd was proportional to the Ko A value. These data show that changes in Qd alter small solute clearances greater than predicted assuming a constant Ko A.

Hypoxia during haemodialysis, mainly acetate, has been reported several times. In our study we have monitored oxygen status during 258 bicarbonate haemodialyses. A significant drop below 80 mmHg in mean oxygen tension occurred. Mean oxygen saturation reflected this drop but did not reach levels below 90%. The mean oxygen concentration was on the whole critical low, though slightly increasing during each haemodialysis session due to ultrafiltration. It is concluded that both hypoxia and hypoxaemia do occur during bicarbonate haemodialysis. To a group of patients generally having limited cardiac reserves, a poor oxygen status is a potentially serious complication to haemodialysis. Monitoring oxygen status is thus advisable.

Hemodialfiltration (HDF) has shown good efficiency and cardiovascular stability in stable young hemodialysis patients. The aim of this work was to verify whether this is also valid for a population above the age of 65 on bicarbonate dialysis (BD) with frequent intradialytic hypotension episodes and dialysis intolerance.

Objective The evaluation of the efficacy, adequacy, clinical tolerance, and safety of a new bicarbonate continuous ambulatory peritoneal dialysis (CAPD) solution. Design and Patients A 6–week cross-over clinical study in 6 stable CAPD patients was performed. After a control period (2 weeks) with a standard CAPD solution (lactate, 35 mmol/L), a two-chamber bag containing 34 mmol/L of bicarbonate was used for 4 weeks. A breakable valve divided the two chambers, one containing bicarbonate and the other calcium. The two solutions were mixed just before use, thus avoiding the calcium and magnesium carbonate precipitation. Results No differences between control and study periods were found for blood urea nitrogen, creatinine, total proteins, albumin, total and ionized calcium, phosphate, sodium, potassium, chlorine, and hemoglobin. Blood bicarbonate significantly increased from 21.25±2.02 to 23.36±1.15 (pConclusion A CAPD bicarbonate solution is effective in uremic acidosis correction, does not affect dialysis adequacy, is safe, and well tolerated.

Introduction About ten years ago it was discovered that changes in filter design which increase passive filtration improved dialysis efficiency. Later, these modified membranes showed similar intradialytic efficiency when used in on-line hemodiafiltration or in bicarbonate dialysis, called internal hemodiafiltration. Aim and Methods On the basis of these previous results, we studied the long-term effects of internal hemodiafiltration, in comparison with low-flux bicarbonate dialysis. The pre-dialysis beta2-microglobulin level was chosen as the primary outcome variable. A prospective multicenter study with a cross-over scheme, 2 treatments and 3 periods, was designed. Twenty-four patients, followed in two dialysis centers, were enrolled. Many other parameters were measured every month at the first dialysis session of the week. The intra-dialytic removal of urea, beta2-microglobulin and homocysteine was also calculated. Results The removal of uremic toxins was significantly higher in internal hemodiafiltration than in low-flux bicarbonate dialysis. The pre-dialysis value of urea, phosphorus, beta2-microglobulin and homocysteine was lower during internal hemodiafiltration as compared with low-flux bicarbonate dialysis. The mean pre-dialysis value of hemoglobin was significantly higher during internal hemodiafiltration than low-flux bicarbonate dialysis, with a trend towards a significantly lower consumption of erythropoiesis stimulating agents during internal hemodiafiltration as compared with low-flux bicarbonate dialysis. Conclusions Long-term treatment with internal hemodiafiltration improves the removal of small molecules and stops the continuous increase of middle molecules as seen in low-flux bicarbonate dialysis. Internal hemodiafiltration may substitute low-flux bicarbonate dialysis, but we need new prospective studies about long-term hard end-points.

Lithium is used to treat manic-depressive disorders, but toxic side effects commonly occur. The preferred treatment of severe lithium intoxication is hemodialysis. No data, however, exist comparing the effectiveness of acetate to bicarbonate dialysis for the removal of lithium. We present a case of lithium intoxication treated with both. During acetate dialysis, lithium removal occurred exclusively from the extracellular fluid space, while during bicarbonate dialysis, lithium removal occurred equally from both the extracellular and intracellular fluid spaces. We hypothesize that acetate but not bicarbonate activates the sodium-hydrogen antiporter on cell membranes, and that lithium, substituting for sodium, is driven into cells. This may explain the rebound in lithium levels commonly noted after conventional dialysis. We recommend bicarbonate hemodialysis as the therapy of choice for severe lithium intoxication.

Recently introduced algorithms for determination of the arterial oxygen extraction tension (px), oxygen compensation factor (Qx), total oxyg

In hemodialysis, bicarbonate (HCO3−) balance may be affected by the choice of HCO3− concentration in the dialysis fluid. In online postdilution hemodiafiltration (HDF), we studied the effect of three various HCO3− dialysis fluid concentrations on HCO3− transport across the hemodialyser membrane and on the final HCO3− balance for the in vitro patient.

The last decade has seen not only an enormous growth in the number of hemodialysis patients but also a concomitant growth in the number of hemodialysis machines produced every year by fewer companies than 10 years ago. Because the risk of accidents increases with the number of different machines in the field, standard organizations and government authorities worldwide have issued standards and laws that regulate the design of hemodialysis machines. Both effects have slowed the development of new concepts and the effective use of modern technology in hemodialysis machines. The extracorporeal circuit has remained unchanged for more than twenty years. Bicarbonate dialysis with single patient machines and volumetric ultrafiltration control which were developed in the late 70s took more than 10 years to be generally accepted. Cost pressure has been an effective driving force for the introduction of new technology. High-efficiency dialysis was introduced in order to reduce treatment time. Underdialysis of many patients was the result because in many cases the shortening of the treatment time was not sufficiently compensated for by the increased efficacy of the dialysis process

Bicarbonate as a physiological buffer should be preferred in haemodialysis treatments. The use of bicarbonate dialysis, however, varies from 30 to 100% in the different industrialised countries. Except for the many advantages using bicarbonate dialysate, there are also clinical pitfalls in the use of the bicarbonate buffer substrate. Furthermore, technical problems can be expected in the use of varying dialysate bicarbonate concentrations, as in the concomitant use of acetate and bicarbonate dialysate in the same dialysis unit. This paper deals with the clinical and technical aspects of bicarbonate dialysis.

Bicarbonate dialysis has several clinical advantages compared to conventional acetate hemodialysis. However, the use of bicarbonate in the dialysate requires complicated hardware with considerable maintenance and servicing. We have developed a new dialysis technique, a modification of hemodiafiltration, called acetate-free biofiltration (AFBF), with no base replacement agents in the dialysate and with the infusion of bicarbonate solution in postdilution fluid. This study consisted of two parts, an acute phase (8 dialysis patients) and a chronic phase (4 patients) lasting up to 12 months. In the first phase we evaluated the effects of different amounts of infused bicarbonate (from 751 to 1,002 mEq per session) on acid-base balance. The best correction of uremic acidosis was obtained with the infusion of 900-1,000 HCO3 mEq during a 3-hour AFBF. There was a significant (p less than 0.0001) positive correlation between infused and gained bicarbonate. In the chronic part, 880-910 HCO3 mEq was infused per session and there was an increase in mean pretreatment plasma bicarbonate from 18.1 +/- 2.2 upon starting to 22.8 +/- 0.4 mEq/l by the end of the 12-month period. A very low incidence of intradialytic hypotension and stable serum chemistries were achieved with this technique as compared with standard hemodialysis despite a reduction of 3 h in weekly treatment time. AFBF is an easy-to-use, safe alternative to bicarbonate dialysis thanks to the absence of pyrogen reactions and comparatively low-cost maintenance.

During hemodialysis, ultrafiltration (UF) seems to affect the dialytic dose because of convective removal of urea and contraction of its distribution volume. We aimed to assess whether the adoption of a decreasing UF profile could yield a different dialytic dose from that obtained with a constant UF mode. Ten patients were randomly assigned to undergo 12 sessions with a constant UF mode (phase A) followed by 12 sessions with a decreasing UF rate (phase B), or the reverse. Kt/V and urea reduction ratio (URR) were 1.77 +/- 0.26 and 70.02 +/- 8.26% in phase A vs. 1.81 +/- 0.36 and 71.02 +/- 6.48% in phase B, respectively, showing no significant difference. Measurement of the differences in volemic variations between the two phases showed a statistically significant difference at the second hour (P < 0.001, the volemic reduction being greater in phase B than A) and at the fourth hour (P < 0.001, being greater in phase A than B). In standard bicarbonate dialysis, the adoption of a decreasing UF profile rather than a constant one does not alter the efficiency of the dialytic treatment.

A therapy-specific worsening of cardiovascular stability during bicarbonate dialysis (BD) with respect to acetate-free biofiltration (AFB) have been previously reported. We further investigated the impact of the 2 therapies on electrocardiographic parameters in order to gain novel insight into the cardiac responses. Holter ECG acquired during hypotension-free sessions (12 BD + 12 AFB) were retrospectively analyzed. R-R intervals were extracted from ECG recordings. An autoregressive spectral technique was used to compute low- and high-frequency (LF and HF) components of heart rate variability (HRV). QT interval duration was measured with a computer-assisted technique and corrected for HR. In BD the LF component of HRV after an initial increase was slowly depressed with respect to AFB (p < 0.05). QT duration showed a significant (p < 0.01) hemodialysis-induced reduction. QT shortening was more pronounced (p < 0.05) in BD than in AFB (-31 vs. -10 ms), even after correction for HR (p < 0.05). Cardiac electrical activity is significantly affected by the hemodialysis technique. The decrease in the LF component of HRV and the QT shortening are coherent with the worse cardiovascular tolerance observed in BD and with the hypothesis of an enhanced production of endogenous nitric oxide.

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.

Severe metabolic acidosis may occur during hemodialysis when the incorrect acid dialysis concentrate from a two-part bicarbonate dialysis system is used in an acetate dialysis machine. We deliberately applied this technique to correct severe metabolic alkalosis in a patient with chronic renal failure. Rapid correction of the metabolic alkalosis was achieved and the procedure was well tolerated.