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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.

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.

Aim To evaluate the effects on glycemic excursions during bicarbonate dialysis (BHD) compared to hemodiafiltration (HDF) in type 2 diabetic or not diabetic patients affected by end-stage renal disease (ESRD). Material and Methods Thirty-six patients (20 affected by type 2 diabetes mellitus, and 16 not diabetic patients) were evaluated and underwent BHD dialysis, followed by HDF dialysis two days later. All patients underwent also glucose continuous monitoring system, using i Pro Continuous Glucose Monitor System (Medtronic MiniMed) starting just before the BHD, and ending five days later, two days after the HDF dialysis. Glycemic control was estimated as the mean blood glucose (MBG), the area under the glucose curve above 70mg/dl (AUC >70 ) or 180mg/dl (AUC >180 ), and the percentage of time above 70mg/dl (t >70 ) or 180mg/dl (t >180 ). Intraday glycemic variability was assessed as the standard deviation (SD), M value, and the mean amplitude of glycemic excursions (MAGE). Day-to-day glycemic variability was assessed as the mean of daily difference (MODD), that is the mean of the absolute difference among glucose values taken on 2 consecutive days at the same time. Results glycemic control was better with HDF: MBG, and AUC >180 were lower during HDF compared do BHD. We also observed a significant decrease of glycemic excursions during HDF dialysis: SD, M value, and the MAGE value were lower with HDF. The MODD value was significantly changed in BHD group, while no differences were recorded during HDF. Conclusion HDF seems to greater reduce glycemic excursions during the treatment compared to BHD.

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.

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.

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.

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.

Patients on chronic hemodialysis often portray high serum [K+]. Although dietary excesses are evident in many cases, in others, the cause of hyperkalemia cannot be identified. In such cases, hyperkalemia could result from decreased potassium removal during dialysis. This situation could occur if alkalinization of body fluids during dialysis would drive potassium into the cell, thus decreasing the potassium gradient across the dialysis membrane. In 35 chronic hemodialysis patients, we compared two dialysis sessions performed 7 days apart. Bicarbonate or acetate as dialysate buffers were randomly assigned for the first dialysis. The buffer was switched for the second dialysis. Serum [K+], [HCO3-], and pH were measured in samples drawn before dialysis; 60, 120, 180, and 240 min into dialysis; and 60 and 90 min after dialysis. The potassium removed was measured in the dialysate. During the first 2 hr, serum [K+] decreased equally with both types of dialysates but declined more during the last 2 hr with bicarbonate dialysis. After dialysis, the serum [K+] rebounded higher with bicarbonate bringing the serum [K+] up to par with acetate. The lower serum [K+] through the second half of bicarbonate dialysis did not impair potassium removal (295.9 ± 9.6 mmol with bicarbonate and 299.0 ± 14.4 mmol with acetate). The measured serum K+ concentrations correlated with serum [HCO3-] and blood pH during bicarbonate dialysis but not during acetate dialysis. Alkalinization induced by bicarbonate administration may cause redistribution of K during bicarbonate dialysis but this does not impair its removal. The more marked lowering of potassium during bicarbonate dialysis occurs late in dialysis, when exchange is negligible because of a low gradient. Fil: Capdevila, M.. Fundación Robert Cade, Instituto de Especialidades Médicas; Argentina Fil: Martinez Ruiz, I.. Fundación Robert Cade, Instituto de Especialidades Médicas; Argentina Fil: Ferrer, C.. Fundación Robert Cade, Instituto de Especialidades Médicas; Argentina Fil: Monllor, F.. Fundación Robert Cade, Instituto de Especialidades Médicas; Argentina Fil: Ludjvick, C.. Fundación Robert Cade, Instituto de Especialidades Médicas; Argentina Fil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Juncos, Luis Isaias. Fundación Robert Cade, Instituto de Especialidades Médicas; Argentina

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.

Pyrogenic reactions (PR) are a well-recognized complication of hemodialysis and have been associated with dialyzer reuse, high-flux dialysis, and bicarbonate dialysate. However, the roles of bacteria and endotoxin in dialysate for producing PR are not well defined. To determine the effect of removing most bacteria and endotoxin from the dialysate on the incidence of PR, a cohort of chronic hemodialysis patients receiving high-flux, high-efficiency, or conventional hemodialysis at three centers with bicarbonate dialysis fluids that had been filtered with a polysulfone high-flux hemodialyzer was prospectively studied. Unfiltered bicarbonate concentrate had median bacterial and endotoxin concentrations of 479,000 CFU/mL and 39,800 pg/mL, respectively. After filtration of the bicarbonate concentrate at the central proportioner, dialysate had a median 9.2 CFU/mL of bacteria and 17.8 pg/mL of endotoxin. Dialysate filtered at individual proportioning dialysis machines had a median 0.001 CFU/mL of bacteria and 0.19 pg/mL of endotoxin. Nine PR were identified among 303 patients after 28,007 hemodialysis treatments (0.3 PR/1,000 treatments). The rate of PR was similar for the three hemodialysis treatment modalities and for first-use compared with reused dialyzers. Although the PR rate in this study was lower (P = 0.046) than the PR rate of a previous study with unfiltered dialysis fluids (0.7 PR/1,000 treatments), it represents a difference of only 10 PR in over 28,000 treatments. It was concluded that filtration of hemodialysis fluids is efficacious in removing bacterial and endotoxin contamination and can result in a lower incidence of PR in patients receiving high-flux, high-efficiency, or conventional hemodialysis.

Using kinetic modelling for shaping profile dialysis, we present a promising approach to improve the cardiovascular stability of patients during dialysis treatment. In order to obtain an insight into the physiological mechanisms of increased stability, a model considering alterations of electrolytes and water distribution and of acid-base status was developed. This algorithm was used for the evaluation of 114 dialysis sessions, which were performed with highly individualised profiles. Each profile was developed for one patient by trying empirically to prevent episodes of hypotension as well as other clinical problems throughout dialysis. The main advantage of profile dialysis compared to standard bicarbonate dialysis, for example, is a reduced water influx into the cell during the treatment. According to our clinical and theoretical results a correlation between water influx into the cell and time of occurrence of hypotensive episodes in individuals can be assumed. Hypotension usually starts after 0.5 litres of water have entered the intracellular space, regardless of the time necessary for this fluid shift.

The use of bicarbonate dialysate as the buffer during routine dialysis is growing. This discussion reviews several of the comparative trials in which bicarbonate and acetate buffers have been tested. Effects of the two buffers on BP, cardiac function, and pulmonary performance are discussed. Costs of the two systems are also compared. Patients who seem most likely to benefit from bicarbonate dialysate include those with a reduced muscle mass in whom a high sodium dialysate has not prevented hypotension.

Acetate and bicarbonate fluctuations and acetate intolerance during dialysis. Plasma bicarbonate losses during acetate dialysis were prevented by using a combination of acetate and bicarbonate in the dialysate. In 21 patients who were treated with combination dialysate, the fall in mean blood pressure (MBP), and frequency of symptoms, and post-dialysis task performance were all similar to that observed during dialysis with acetate alone. Furthermore, dialysis performed with bicarbonate dialysate resulted in significantly smaller MBP drops, fewer symptoms, and an improved task performance compared to either an acetate or a combination dialysis. These findings indicate that the presence of acetate, rather than a bicarbonate loss, was responsible for the patients' intolerance to acetate dialysis. Patients symptomatic on acetate dialysis had a similar ultrafiltration rate, weight loss, MBP drops, and postdialysis serum acetate levels; they were similar in age and weight to symptom-free patients. Thus, the toxic effect of acetate was not related to serum acetate level. There was no difference in bicarbonate dialysis between patients with symptoms on acetate and the symptom-free patients in reference to MBP drops and task performance. This finding suggests that symptomatic patients were not simply less tolerant to the process of dialysis, but differed from symptom-free patients in their response to the presence of acetate. Fluctuation de l'acetate et du bicarbonate, et intolerance a l'acetate pendant la dialyse. Les pertes en bicarbonates plasmatiques au cours de dialyses avec l'acetate ont ete prevenues en utilisant un melange d'acetate et de bicarbonate dans le dialysat. Chez 21 malades dialyses avec ce melange, la chute de la pression arterielle moyenne (PAM), la frequence de symptomes, et la performance a l'effort apres la dialyse etaient similaires a ce qu'elles etaient lors des dialyses contre de l'acetate seul. De plus, la dialyse contre un dialysat avec du bicarbonate s'accompagnait de chutes de PAM significativement plus faibles, de moins de symptomes, et ameliorait la performance a l'effort par rapport a la dialyse avec acetate ou avec le melange. Ces resultats indiquent que c'est la presence d'acetate, plus que la perte de bicarbonate qui est responsable de l'intolerance des malades lors d'une dialyse avec acetate. Les malades symptomatiques lors des dialyses a l'acetate avaient des taux d'ultrafiltration, une perte de poids, des chutes de PAM et des taux d'acetate plasmatique postdialyse identiques a ceux des malades asymptomatiques et etaient d'âge et de poids egaux. Ainsi, la toxicite de l'acetate n'etait pas en rapport avec la concentration d'acetate serique. Dans le cas des dialyses avec bicarbonate, il n'y avait pas de difference entre les malades symptomatiques avec l'acetate et les malades asymptomatiques, qu'il s'agisse des chutes de PAM ou de la performance a l'effort. Ce fait suggere que les malades symptomatiques n'etaient pas simplement moins tolerants a la dialyse en soi mais differaient des malades asymptomatiques par leur reponse a la presence d'acetate.

Twenty uremic patients submitted to three different dialytic procedures (6 patients to acetate dialysis, 8 patients to bicarbonate dialysis, 6 patients to hemofiltration) were monitored in respect to the hemodynamic parameters recorded with a thermistor Swan-Ganz catheter. During acetate dialysis there was an increment of cardiac index (CI) up to positive values (+4.8%), while resistance index (RI) decreased progressively until it reached -16.5%. During bicarbonate dialysis CI, after an initial fall, remained constant and RI increased (+8.6%). During hemofiltration CI decreased constantly throughout the entire procedure while RI increased until +12.9%. We concluded that during diffusive transport the buffer used plays an important role in determining hemodynamic responses to fluid removal; during convective transport vascular resistance increases in spite of acetate.

Model-based study of the effects of the hemodialysis technique on the compensatory response to hypovolemia.BackgroundHemodialysis technique (dialysate composition, filter, convection/diffusion ratio, etc.) can have an impact on the patient's tendency to acute hypotension. We have examined the hypothesis that the dialysis technique affects the hypotension risk by altering the cardiovascular compensatory response to hemodialysis-induced hypovolemia.MethodsTwelve hypotension-prone subjects were studied during six sessions of conventional bicarbonate dialysis (BD) and six sessions of acetate-free biofiltration (AFB). Blood volume (BV) control system was used in AFB to provide a BV change equivalent to the BV change observed in BD. The efficacy of reflex compensatory mechanisms was assessed by a model-based computer analysis of the BD and AFB sessions.ResultsBD sessions were complicated by hypotension more frequently than the AFB ones (34/66BD vs. 18/66AFB). Hypotension arose about 60 minutes earlier in BD (123 ± 41 minutes in BD vs. 183 ± 25 minutes in AFB, P < 0.01), and after a smaller BV reduction (hypotension BV 7.9%± 2.0% in BD vs. 10.9%± 2.6% in AFB, P < 0.05). Model-based computer analysis of the sessions without hypotension revealed differences in peripheral resistance adaptation (9%± 9% BD vs. 19%± 7% AFB, P < 0.05) as well as in the stroke volume reduction (19%± 8% BD vs. 10%± 8% AFB, P < 0.001). Model analysis of sessions with hypotension indicated that compensatory mechanisms were almost inoperative in BD, whereas a residual capacity to control peripheral resistance and cardiac contractility was present in AFB. Model simulations demonstrated that hypotension occurred later in AFB since the residual compensatory capacity in AFB was able to sustain the arterial pressure for larger BV reductions (8.3% BD vs. 11.2% AFB).ConclusionThe increased risk of acute hypotension in BD compared to AFB is caused by a therapy-induced inhibition of reflex compensatory response to hypovolemia.

Two patients with profound dialysis-induced hypotension were seen, in both of whom sequential ultrafiltration and haemodialysis failed to alleviate their symptoms; in one bicarbonate dialysis similarly produced no improvement. The hypotension was frequently severe enough to necessitate premature termination of the dialysis. Haemofiltration was associated with almost total resolution of symptoms, adequate biochemical control of uraemia, and satisfactory removal of weight gain between dialysis sessions. Profound hypotension during dialysis may become more common as older patients enter dialysis programmes; haemofiltration is a valuable technique in such cases.

To reduce the cost of hemodiafiltration (HDF), a standard hemodialysis machine was modified to permit in-line production of substitution fluid from bicarbonate dialysate. The authors' present data showing that this procedure was made bacteriologically safe; was simple to use, and offered a cheap approach to perform high-flux HDF using a hemodifilter of relatively small membrane surface area.

Eight patients were studied during four sessions of acetate-free biofiltration (AFBF). AFBF is a new dialysis technique with no base replacement agents in the dialysate and with the addition in postdilution mode of bicarbonate (HCO3) solution directly into the extracorporeal blood circuit. In this study the effects on acid-base balance of different infusions of sodium bicarbonate (NaHCO3) ranging from 751 to 1,002 mEq per session was evaluated. There were significant positive correlations between the HCO3 infused and net HCO3 gained (r = 0.776, p less than 0.0001) and between HCO3 infused and plasma intratreatment HCO3 changes (n = 0.562, p less than 0.001). Stepwise multiple linear regression analysis demonstrated that HCO3 infused and plasma predialysis HCO3 values played the major role in HCO3 balance in AFBF. The best correction of metabolic acidosis was obtained with the infusion of 900-1,000 mEq of HCO3. The use of substitution fluid with 145 mEq/L of Na concentration avoids the risk of a positive intratreatment Na balance.

To evaluate the role of bicarbonate loss through the dialyser and acetate flux to the patient in the development of symptoms during acetate dialysis, bicarbonate loss during acetate dialysis was prevented by using a combination of acetate and bicarbonate in the dialysate. Seven uraemic patients were treated for 4 months with acetate dialysis and, successively, for a similar period of time with bicarbonate, and a combination of acetate and bicarbonate dialysis. Blood-pressure drop and the incidence of hypotension and symptomatic episodes were similar in bicarbonate and combination dialysis, and significantly lower than in acetate dialysis. Serum acetate concentrations were similar during acetate and combination dialysis. These findings indicate that bicarbonate loss rather than the presence of acetate was responsible for the patients' intolerance to acetate dialysis.

Hyperacetataemia during acetate haemodialysis has been associated with the development of a variety of unpleasant symptoms, although a direct toxic effect of acetate is hard to prove. Acetaldehyde, which is produced during the metabolism of ethanol to acetate, has various toxic effects including some of those reported during acetate dialysis such as nausea, headache and palpitations. Using a novel, recently developed method we studied blood acetaldehyde concentrations during acetate dialysis in 15 patients and found significant increases in five, with a mean peak value in these patients of 1.36 mumol/l (normal less than 0.4 mumol/l). These five patients also developed high blood acetate concentrations during a subsequent acetate dialysis and showed a significant correlation between blood acetaldehyde and acetate concentrations (r = 0.55, P less than 0.05). Blood acetaldehyde did not change during bicarbonate dialysis in these patients. Our results suggest that significant accumulation of acetaldehyde may occur during acetate dialysis, especially in those patients whose metabolic capacity for acetate is somehow impaired, and that acetaldehyde may contribute to some of the symptoms previously ascribed to 'acetate' intolerance.

We present an original method for the preparation of "stable" dialysate containing 35 mEq/l of bicarbonate. The dialysate was utilized with 4 patients for periods ranging from 4 months to 1 year according to a short-term recirculated dialysis schedule in closed circuit (20-40L) (2-2 1/2 hrs) on alternate days. Preliminary results are reported here with respect to the tollerance of the dialytic run and correction of the acid-base balance equilibrium. The clinical tollerance is excellent despite high dehydration rates even in patients particularly sensitive to ultrafiltration. The acidosis correction would seem to be much better with bicarbonate than with traditional dialysis. The difference is even higher if we consider the brevity of the dialysis. During the bicarbonate dialysis we do not observe any fall of the PCO2 or significant difference in PO2 in the patient's blood. The correction of acidosis probably causes the normalization of pre-dialytic potassiemia in spite the "net" removal of K with short dialysis is considerably less.

Severe metabolic acidosis occurred during bicarbonate hemodialysis as the result of an error made in the selection of the dialysate concentrate. We questioned whether or not it was possible for the dialysis equipment to regulate the proportions in the dialysate fluid using an incorrect dialysate concentrate and still obtain the proper conductivity. We simulated this situation in vitro and found that during bicarbonate dialysis an inappropriately acidic dialysate fluid could replace the normal dialysate with an adequate range of conductivity still being maintained and therefore no triggering of alarms. The investigation showed that the dialysis machines were not adequately adjusted for sensitivity to the concentrates being employed during dialysis. We concluded that dialysis equipment should be fitted with on-line pH meters with alarm systems.