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which is found in some HD patients&#44; may be controlled using acetate-free dialysate&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">In terms of HD technique&#44; convective therapies are associated with better tolerance and clearance of larger molecules as compared with conventional HD treatments&#46;<span class="elsevierStyleSup">6</span> These techniques have shown good cardiovascular stability with the use of more biocompatible membranes and ultrapure endotoxin-free dialysate&#46; Recently&#44; a new pre-dilution convectional technique has been described on-line PHF&#44; which uses a double chamber dialyser and allows reinfusion of large amount of substitution fluid than conventional post-dilution techniques&#46;<span class="elsevierStyleSup">7&#44;8</span> On-line PHF has proven to be a safe technique in both children and adults allowing greater &#946;2-microglobulin clearance with good clinical tolerance&#46;<span class="elsevierStyleSup">9&#44;10</span></p><p class="elsevierStylePara">The purpose of this study was to evaluate and compare the changes in biochemical and clinical data during dialysis by subjecting the same patient to three different dialysis techniques&#58; high-flow HD&#44; on-line PHF with conventional dialysate and on-line PHF with acetate-free DF&#44; using HCl&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">PATIENTS AND METHODS</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patients</span></p><p class="elsevierStylePara">Thirty-five clinically stable HD patients &#40;20 men and 15 women&#41; from six level-3 hospitals in Spain &#40;Madrid&#44; C&#243;rdoba&#44; Santander and Barcelona&#41; were selected for the study&#46; All patients gave informed consent to participate in the study and the study was approved by the six hospitals&#8217; ethics committees&#46;</p><p class="elsevierStylePara">The inclusion criteria were as follows&#58; aged over 18&#59; undergoing HD for more than three months who were stable on three weekly sessions of 3 to 5 hours a stable regimen of anticoagulation and erythropoietin&#59; haematocrit higher than 28&#37; and vascular access allowing flows greater than 250ml&#47;min&#46;</p><p class="elsevierStylePara">Patients with known coagulation problems were excluded from the study as were those with a survival rate lower than 18 months or with significant residual renal function &#40;diuresis greater than 400ml&#47;day or creatinine clearance &#62; 2ml&#47;min&#41;&#46;</p><p class="elsevierStylePara">The patients had a mean age of 62 &#177; 14 years &#40;range 24-81&#41; and the mean duration of HD treatment was 67 &#177; 57 months &#40;range 4-249&#41; &#40;table 1a&#41;&#46;</p><p class="elsevierStylePara">The aetiology of renal failure was glomerulonephritis &#40;n &#61; 5&#41;&#59; interstitial nephritis &#40;n &#61; 8&#41;&#59; polycystic kidney disease &#40;n &#61; 5&#41;&#59; arterial hypertension &#40;n &#61; 7&#41;&#59; diabetes mellitus &#40;n &#61; 2&#41;&#59; and unknown &#40;n &#61; 8&#41;&#46;</p><p class="elsevierStylePara">The Charlson comorbidity index was 5&#46;2 &#177; 2&#46;4 &#40;range 2-12&#41;&#44; &#40;table 1a&#41;&#46;</p><p class="elsevierStylePara">Table 1b shows the characteristics of the 21 patients who completed the study&#46; There were no significant differences between the 35 patients selected and the 21 who completed the study&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dialysis technique and study design</span></p><p class="elsevierStylePara">All patients underwent dialysis for 3-4 hours thrice weekly using conventional bicarbonate concentrate with acetate &#40;BHD3 A4&#44; Fresenius Medical Care&#44; Bad Homburg&#44; Germany or Dialisan-Bicart Ca 30&#44; Hospal&#44; Lyon&#44; France&#41;&#46; All HD machines were equipped with endotoxin filters &#40;Bellco&#44; Mirandola&#44; Italy&#41;&#46; Daily diuresis was less than han 150ml&#47;24 hours and mean dry weight was 65&#46;2 &#177; 13kg &#40;47-100&#41;&#46; The mean Kt&#47;V &#40;Daugirdas 93&#41; was 1&#46;26 &#177; 0&#46;24&#44; the mean Qb was 345 &#177; 40ml&#47;min&#44; the Qd was fixed for all at 500ml&#47;min&#46; Interdialytic weight gain was 1&#46;8 &#177; 0&#46;75kg&#46;</p><p class="elsevierStylePara">Total mean conductivity was 13&#46;9 &#177; 0&#46;1ms&#47;cm and mean bicarbonate conductivity was 3&#46;1 &#177; 0&#46;1ms&#47;cm and both remained constant for all patients during the study&#46; The temperature of the DF was fixed at 36&#186; C for all patients in all the centres during the study&#46; All patients used high permeable synthetic membranes during the first three months of the study&#46; When the technique was changed to on-line PHF&#44; the membranes were substituted by double chamber polyethersulfone dialysers&#46; The mean volume of liquid infused during pre-dilution was 10L&#47;hour&#46;</p><p class="elsevierStylePara">All the patients underwent conventional HD for three months and one group was then randomised to on-line PHF technique using a conventional concentrate with bicarbonate for six months and then changed to on-line PHF with acetate-free concentrate &#40;611 free-acetate&#44; Bellco&#44; Mirandola&#44; Italy&#41;&#46; The other group reversed these two periods&#46; The patients were randomised by centre and allocation order&#46; Blood tests were performed monthly throughout the study&#46; Clinical data was collected during 13 consecutive sessions at baseline and at 3&#44; 6&#44; 9&#44; 12 and 15 months&#46;</p><p class="elsevierStylePara">The three techniques used during the study were performed using the Formula dialysis machine &#40;Bellco&#44; Mirandola&#44; Italy&#41;&#46;</p><p class="elsevierStylePara">HD tolerance was evaluated as in terms of number of hypotensive episodes&#44; headaches&#44; pruritus&#44; vomiting or cramps per month&#46;</p><p class="elsevierStylePara">Episodes of hypotension were defined as a fall in systolic blood pressure&#44; below 95mmHg associated with symptoms requiring the intervention of healthcare professionals&#46;</p><p class="elsevierStylePara">Monthly blood tests performed pre and post-HD included urea&#44; creatinine&#44; sodium&#44; potassium&#44; chloride&#44; bicarbonate&#44; acetate&#44; calcium&#44; phosphate&#44; glucose&#44; albumin&#44; &#946;2-microglobulin and C-reactive protein &#40;CRP&#41;&#46; The latter was analysed using nephelometry &#40;ultrasensitive CRP&#44; Behring Diagnostics&#44; GMBH&#44; Rarburg&#44; Germany&#41; with a detection limit of 0&#46;1mg&#47;ml and a reference range between 0&#46;1 and 0&#46;4mg&#47;L&#46; The coefficient of variation was lower than 4&#37;&#46;</p><p class="elsevierStylePara">The following were measured pre-dialysis&#58; uric acid&#44; total cholesterol&#44; HDL cholesterol&#44; triglyceride&#44; total proteins&#44; prealbumin&#44; ferritin&#44; transferrin saturation index&#44; serum iron&#44; parathyroid hormone&#44; haematocrit&#44; haemoglobin&#44; fibrinogen and homocysteine&#46;</p><p class="elsevierStylePara">Serum acetate was determined by the ultraviolet radiation method&#46; The enzymatic reaction in acetate synthesis results in the formation of NADH&#43; measured as an increase in absorbency&#46; Normal values in the healthy population were lower than 0&#46;1mmol&#47;L with a detection limit of 0&#46;01mmol&#47;L&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Preparing the acetate-free DF</span></p><p class="elsevierStylePara">All the electrolytes&#44; except from bicarbonate&#44; were present on the concentrate&#46;The acetic acid was substituted by HCl &#40;Bellco-Soludia&#44; Fourquevaux&#44; France&#41;&#46; The pH of the concentrate was then less than 1&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">The data are expressed as mean &#177; standard deviation&#46; The Kolmogorov-Smirnov test was used to evaluate the normal distribution of the variables&#46; All the variables had normal distribution with the exception of CRP which had an exponential curve and required logarithm transformation&#46; For parametric variables&#44; the paired t-test was used for two measurements and the ANOVA test for more than two&#46;</p><p class="elsevierStylePara">For non-parametric variables&#44; the Wilcoxon test was used for two measurements and the Dunett&#8217;s test for more than two&#46; The Friedman test was used to evaluate the effect of the different treatments on HD tolerance&#46;</p><p class="elsevierStylePara">The X<span class="elsevierStyleInf">2</span> test was used for categorical variables&#46; All the data were analysed using the SPSS version 12&#46; Statistical significance was defined as p &#60; 0&#46;05&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">The study lasted 15 months&#46;</p><p class="elsevierStylePara">Of the 35 patients 30 were randomised&#46; Of these four died&#44; five received a kidney transplant and 21 completed the study&#46;</p><p class="elsevierStylePara">During the first six months&#44; 12 patients were randomised to on-line PHF with conventional DF and 18 patients were randomised to on-line PHF with acetate-free DF&#46; The groups then switched to the alternative treatment for a further 6 months&#46;</p><p class="elsevierStylePara">No significant differences were found in the biochemical parameters&#44; except for post-dialysis chloride level and pre and post-dialysis bicarbonate&#46; Dry weight and interdialytic weight gain remained stable during the entire study &#40;table 2&#41;&#46;</p><p class="elsevierStylePara">The pre-dialysis plasma acetate levels during the conventional HD treatment period and the acetate-free on line PHF &#177; standard deviation of the concentrate did not differ statistically from the group treated with on-line PHF with HCl concentrate &#40;0&#46;10 &#177; 0&#46;09 vs&#46; 0&#46;09 &#177; 0&#46;07mmol&#47;L&#44; p &#61; ns&#41;&#44; while the post-dialysis acetate levels were significantly higher during the treatment period with acetic acid concentrate in comparison to the treatment with HC1 concentrate &#40;0&#46;24 &#177; 0&#46;16 vs&#46; 0&#46;15 &#177; 0&#46;13&#44; p &#61; 0&#44;000&#41; &#40;table 2&#41;&#46;</p><p class="elsevierStylePara">There were no significant differences in the nonphysiological values of acetate in pre-dialysis &#40;26&#37; of patients using DF with acetate&#44; 17&#37; of patients using DF with HC1&#44; p &#61; ns&#41;&#46; There were however significant differences between the two treatment periods &#40;with or without acetate&#41; regarding the presence of pathological values of acetate in post-dialysis &#40;61&#37; of patients using DF with acetate vs 30&#37; of patients using DF with HC1&#44; p &#61; 0&#46;000&#41; &#40;figure 1&#41;&#46;</p><p class="elsevierStylePara">On-line HDF with conventional DF was associated with fewer hypotensive episodes than treatment with conventional HD or on-line PHF without acetate &#40;p &#61; 0&#46;019&#41;&#44; &#40;figure 2&#41;&#46; There was no difference in the remaining parameters for dialysis tolerance between the groups but the symptoms&#160; were very low throughout the study&#46;</p><p class="elsevierStylePara">No significant differences were found in the &#946;2-microglobulin reduction rate between conventional HD and convective techniques &#40;table 2&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">With the widespread use of dialysis in patients with multiple co-morbidities &#40;diabetics&#44; advanced age&#44; cardiovascular complications&#41; there is a need for more efficient &#40;better clearance of larger uraemic toxins&#41; and well tolerated &#40;more biocompatible&#41; dialysis techniques&#46;</p><p class="elsevierStylePara">In recent years&#44; pre and post-dilution convective techniques and acetate-free techniques such as acetate-free biofiltration &#40;AFB&#41; led to an improvement in haemodynamic tolerance&#44; correction of the acid-base balance&#44; clearance of larger molecules and greater biocompatibility &#40;ultrapure water&#41; in comparison with conventional HD&#46;<span class="elsevierStyleSup">6&#44;11</span> The present study did not find greater clearance of &#946;2-microglobulin with convective treatment in comparison with conventional HD&#44; however this may be explained by insufficient volumes of pre-dilution reinfusate&#46;</p><p class="elsevierStylePara">When the study was performed&#44; the Formula machine did not allow infusion flows greater than 160ml&#47;min for on-line HDF&#46; This meant that the volume infused was limited to between 28&#46;8 and 38&#46;4L&#46; The comparable volume&#44; in terms of the clearance of medium molecules such as &#8218;&#946;2-microglobulin&#44; is 20L in post-dilution HDF&#44; which would be approximately 60L in pre-dilution HDF&#46;<span class="elsevierStyleSup">12</span></p><p class="elsevierStylePara">As expected&#44; the acetate-free on-line PHF allows the majority of patients to complete treatment with post-HD acetatemia within the physiological range in comparison with the other two techniques which use conventional concentrate with 4mmol&#47;L of acetate&#46; These results are in agreement with other studies&#44; whether using conventional HD and DF with or without acetate or pre-dilution HDF using DF with or without acetate&#46;<span class="elsevierStyleSup">4&#44;5&#44;13</span></p><p class="elsevierStylePara">Recently&#44; Pizzarelli <span class="elsevierStyleItalic">et al&#46;</span><span class="elsevierStyleSup">5</span> reported that the gain in acetate is particularly high in convective treatments and that the plasma levels of acetate return to baseline levels two hours after completing the treatment&#46; In our study&#44; we found no differences in the pre-dialysis values using the concentrate with or without acetate supporting the finding of temporary hyperacetatemia&#46;</p><p class="elsevierStylePara">In this study&#44; there was a reduction in the levels of bicarbonate&#44; pre and post-dialysis&#44; in patients using the acetate-free concentrate&#46; Once in the body&#44; the acetate converts to bicarbonate&#46; Thus&#44; in a patient with bicarbonate levels of 20mmol&#47;L in the plasma pre-dialysis&#44; who undergoes HD with a conventional DF&#44; containing 4mmol&#47;L of acetic acid&#44; in the final positive balance of buffer&#44; approximately 25&#37; corresponds to acetic acid and its metabolisation&#46; With the new acetate-free DF&#44; this component does not exist and therefore to achieve a similar balance the concentration of bicarbonate in the DF needs to be increased&#44; raising its partial conductivity&#46; We suggest that this needs to be increased by 0&#46;2mS&#47;cm&#44; as proposed by Pizzarelli <span class="elsevierStyleItalic">et al</span>&#46; in their study&#46;<span class="elsevierStyleSup">14</span></p><p class="elsevierStylePara">It is known that the acetate induces hypotension by causing vasodilatation and myocardial depression&#46; When we changed from a conventional HD to the convective technique using a standard concentrate&#44; the number of hypotensive episodes was reduced&#46; However it was surprising that when we used acetate-free on-line PHF technique the number of hypotensive episodes increased again &#40;as in the conventional HD treatment period&#41;&#46; One possible explanation for this phenomenon may be that the lower supply of bicarbonate in the acetate-free dialysate group was not compensated for by increasing the bicarbonate conductivity in the machine and&#44; therefore&#44; the tendency towards acidosis resulted in poorer tolerance in the convective technique&#46; In addition to this&#44; the concentration of sodium in the DF has a direct and significant influence on tolerance of dialysis&#46; The ratio between sodium concentration and final conductivity decreases due to the increased concentration of chloride in this new DF&#46; Chloride has a high ionic strenght which significantly contributes to conductivity&#44; with higher strenght than that of acetic acid&#46; Since the machine adjusts dilution based on final conductivity&#44; the increased chloride is compensated with greater dilution of the other elements&#44; with greater proportional influence on sodium&#46; To maintain sodium concentration in acetate-free DF we have to increase the total final conductivity by 0&#46;2mS&#47;cm&#46; It is important to remember that if these adjustments are not made&#44; the patient dialysing with the new acetate-free DF will be more acidotic and the dialysate will have less sodium&#46;</p><p class="elsevierStylePara">Among the multiple factors influencing anaemia in renal failure&#44; is the existence of molecules that accumulate during uraemia which inhibit erythropoiesis&#46;<span class="elsevierStyleSup">15</span> By clearing particles of greater molecular weight&#44; convective techniques allow better control of anaemia and a reduced dose of erythropoietin&#46;<span class="elsevierStyleSup">16 </span>In addition it is known that acetate is a promoter of inflammation and this in turn reduces the response to erythropoietin&#46; We did not find any changes in haemoglobin levels or erythropoietin requirements after changing from conventional HD to the convective technique with or without acetate&#46;</p><p class="elsevierStylePara">It has been suggested that the repeated increase in acetatemia during the dialysis sessions is part of the chronic inflammation presented by patients with renal failure in HD&#46; The exposure to small amounts of acetate during conventional HD is able to induce the production of cytokines by activated polymorphonuclear leukocytes&#44; demonstrated by increased TNF synthesis&#44; serum levels of IL-1&#8218; and nitric oxide synthetase activity&#46;<span class="elsevierStyleSup">17-19</span> The inflammatory parameters evaluated during the study&#44; such as CRP&#44; ferritin and&#47;or albumin&#44; were not modified following the change in technique and&#47;or dialysate&#46; The duration of the study and the small sample size &#40;21&#47;30 patients selected completed the study&#41; may have been insufficient to detect significant changes in these parameters&#46;</p><p class="elsevierStylePara">It is also to be noted that the sample of patients who participated in this study is not representative of the global HD population since&#44; by including patients with good vascular access allowing high blood flows&#44; a population with low prevalence of diabetes mellitus was selected and catheters for vascular access were excluded&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span></p><p class="elsevierStylePara">The on-line PHF technique using an acetate-free concentrate prevents exposure to high concentrations of acetate with the patient achieving the end of the HD session levels of acetatemia within the physiological range&#46; On-line PHF is a pre-dilution PHF treatment with greater tolerance than conventional HD using bicarbonate&#44; that requires high volumes of replacement liquid to achieve effective clearance of molecules with greater molecular weight such as &#946;2-microglobulin&#46; Improvement in tolerance of dialysis may be achieved by the addition of acetate-free DF&#44; but this should be accompanied by increased bicarbonate conductivity &#40;&#43;0&#46;2mS&#47;cm&#41; and total conductivity &#40;&#43;0&#46;2mS&#47;cm&#41; in the HD machine&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgement</span></p><p class="elsevierStylePara">To Sorin Group&#46;</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;t1a&#95;p157&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_t1a_p157.jpg" alt="Characteristics of the patients selected for the study"></img></a></p><p class="elsevierStylePara">Table 1a&#46; Characteristics of the patients selected for the study</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;t1b&#95;p158&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_t1b_p158.jpg" alt="Characteristics of the patients who completed the study"></img></a></p><p class="elsevierStylePara">Table 1b&#46; Characteristics of the patients who completed the study</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;t2&#95;p159&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_t2_p159.jpg" alt="Monitoring of different biochemical parameters pre and post-dialysis"></img></a></p><p class="elsevierStylePara">Table 2&#46; Monitoring of different biochemical parameters pre and post-dialysis</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;f1&#95;p160&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_f1_p160.jpg"></img></a></p><p class="elsevierStylePara">Figure 1&#46; </p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;f2&#95;p160&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_f2_p160.jpg"></img></a></p><p class="elsevierStylePara">Figure 2&#46; </p>"
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        "resumen" => "<p class="elsevierStylePara">Antecedentes&#58; la presencia de ac&#233;tico en el L&#237;quido de Di&#225;lisis &#40;LD&#41; expone al paciente a una concentraci&#243;n de acetato 30-40 veces superior a la normal&#46; Dicha exposici&#243;n aumenta en t&#233;cnicas de Hemodiafiltraci&#243;n &#40;HDF&#41; online&#46; El objetivo de dicho estudio fue evaluar los cambios cl&#237;nico-anal&#237;ticos al usar tres t&#233;cnicas de Hemodi&#225;lisis &#40;HD&#41; diferentes&#46; M&#233;todos&#58; se reclutaron 35 pacientes en HD estable&#46; Se dializaron tres meses con HD convencional y luego fueron aleatorizados para pasar a una t&#233;cnica de PHF on-line con concentrado convencional seis meses&#44; y despu&#233;s pasaron a PHF on-line sin acetato otros seis meses&#46; El otro grupo invert&#237;a estos dos per&#237;odos&#46; Se obtuvieron an&#225;lisis de sangre y datos cl&#237;nicos de HD&#46; Resultados&#58; las medias de los acetatos posdi&#225;lisis fueron significativamente superiores durante los per&#237;odos de tratamiento con ac&#233;tico respecto al per&#237;odo sin acetato&#46; El porcentaje de valores patol&#243;gicos de acetato posdi&#225;lisis fue significativamente superior durante los per&#237;odos de tratamiento con ac&#233;tico &#40;61 respecto al 30&#37;&#41;&#46; Las concentraciones de cloro pos-HD fueron superiores y las de bicarbonato pre y pos-HD fueron menores durante el per&#237;odo sin ac&#233;tico&#46; El n&#250;mero de hipotensiones fue significativamente inferior en el per&#237;odo de PHF on-line con LD est&#225;ndar respecto a los otros per&#237;odos&#46; Conclusiones&#58; la t&#233;cnica de PHF on-line sin acetato disminuye la exposici&#243;n a concentraciones elevadas de acetato y consigue que la mayor&#237;a de pacientes termine la HD con una acetatemia en el rango fisiol&#243;gico&#46; La PHF on-line es un tratamiento de HDF predilucional con mejor tolerancia que la HD est&#225;ndar con bicarbonato&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">Summary Background&#58; the small quantity of acetate present in the dialysis fluid exposes patient&#8217;s blood to an acetate concentration 30-40 times the physiological levels&#46; This amount is even greater in hemodiafiltration on-line&#46; Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient&#46; Methods&#58; 35 patients on hemodialysis were included&#46; All patients were treated with conventional bicarbonate dialysate for 3 months&#44; after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods&#46; Blood samples were drawn monthly throughout the study and clinical data were obtained&#46; Results&#58; Posdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate&#46; Moreover&#44; the percentage of patients with posdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period &#40;61&#37; vs&#46; 30&#37;&#41;&#46; Serum concentrations of chloride posdialysis were higher and serum concentrations of bicarbonate pre and poshemodialysis were lower in the PHF free-acetate period&#46; The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate&#46; Conclusions&#58; PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges&#46; PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate&#46;</p>"
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Acetate-free on-line PHF: how to improve hyperacetatemia and haemodynamic tolerance
PHF on-line sin acetato: como mejorar la hiperacetatemia y la tolerancia hemodinámica
Elisabet Colla, Rafael Pérez-Garcíaa, Angel De Franciscob, Josep Galceranc, Rosa García-Osunac, Alejandro Martín-Malod, MªAntonia Alvarez de Larad, Begoña Sáncheze, A.. Martínez-Castelaoe, Rosa Llopisf
a Hospital Gregorio Marañón, Madrid, Madrid, España,
b Hospital Marqués de Valdecilla, Santander, Santander, España,
c Hospital de Palamós, Palamós, Girona, España,
d Hospital Reina Sofía, Córdoba, Córdoba, España,
e Hospital de Bellvitge, Barcelona, Barcelona, España,
f Clínica Puerta de Hierro, Madrid, Madrid, España,
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which is found in some HD patients&#44; may be controlled using acetate-free dialysate&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">In terms of HD technique&#44; convective therapies are associated with better tolerance and clearance of larger molecules as compared with conventional HD treatments&#46;<span class="elsevierStyleSup">6</span> These techniques have shown good cardiovascular stability with the use of more biocompatible membranes and ultrapure endotoxin-free dialysate&#46; Recently&#44; a new pre-dilution convectional technique has been described on-line PHF&#44; which uses a double chamber dialyser and allows reinfusion of large amount of substitution fluid than conventional post-dilution techniques&#46;<span class="elsevierStyleSup">7&#44;8</span> On-line PHF has proven to be a safe technique in both children and adults allowing greater &#946;2-microglobulin clearance with good clinical tolerance&#46;<span class="elsevierStyleSup">9&#44;10</span></p><p class="elsevierStylePara">The purpose of this study was to evaluate and compare the changes in biochemical and clinical data during dialysis by subjecting the same patient to three different dialysis techniques&#58; high-flow HD&#44; on-line PHF with conventional dialysate and on-line PHF with acetate-free DF&#44; using HCl&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">PATIENTS AND METHODS</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patients</span></p><p class="elsevierStylePara">Thirty-five clinically stable HD patients &#40;20 men and 15 women&#41; from six level-3 hospitals in Spain &#40;Madrid&#44; C&#243;rdoba&#44; Santander and Barcelona&#41; were selected for the study&#46; All patients gave informed consent to participate in the study and the study was approved by the six hospitals&#8217; ethics committees&#46;</p><p class="elsevierStylePara">The inclusion criteria were as follows&#58; aged over 18&#59; undergoing HD for more than three months who were stable on three weekly sessions of 3 to 5 hours a stable regimen of anticoagulation and erythropoietin&#59; haematocrit higher than 28&#37; and vascular access allowing flows greater than 250ml&#47;min&#46;</p><p class="elsevierStylePara">Patients with known coagulation problems were excluded from the study as were those with a survival rate lower than 18 months or with significant residual renal function &#40;diuresis greater than 400ml&#47;day or creatinine clearance &#62; 2ml&#47;min&#41;&#46;</p><p class="elsevierStylePara">The patients had a mean age of 62 &#177; 14 years &#40;range 24-81&#41; and the mean duration of HD treatment was 67 &#177; 57 months &#40;range 4-249&#41; &#40;table 1a&#41;&#46;</p><p class="elsevierStylePara">The aetiology of renal failure was glomerulonephritis &#40;n &#61; 5&#41;&#59; interstitial nephritis &#40;n &#61; 8&#41;&#59; polycystic kidney disease &#40;n &#61; 5&#41;&#59; arterial hypertension &#40;n &#61; 7&#41;&#59; diabetes mellitus &#40;n &#61; 2&#41;&#59; and unknown &#40;n &#61; 8&#41;&#46;</p><p class="elsevierStylePara">The Charlson comorbidity index was 5&#46;2 &#177; 2&#46;4 &#40;range 2-12&#41;&#44; &#40;table 1a&#41;&#46;</p><p class="elsevierStylePara">Table 1b shows the characteristics of the 21 patients who completed the study&#46; There were no significant differences between the 35 patients selected and the 21 who completed the study&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dialysis technique and study design</span></p><p class="elsevierStylePara">All patients underwent dialysis for 3-4 hours thrice weekly using conventional bicarbonate concentrate with acetate &#40;BHD3 A4&#44; Fresenius Medical Care&#44; Bad Homburg&#44; Germany or Dialisan-Bicart Ca 30&#44; Hospal&#44; Lyon&#44; France&#41;&#46; All HD machines were equipped with endotoxin filters &#40;Bellco&#44; Mirandola&#44; Italy&#41;&#46; Daily diuresis was less than han 150ml&#47;24 hours and mean dry weight was 65&#46;2 &#177; 13kg &#40;47-100&#41;&#46; The mean Kt&#47;V &#40;Daugirdas 93&#41; was 1&#46;26 &#177; 0&#46;24&#44; the mean Qb was 345 &#177; 40ml&#47;min&#44; the Qd was fixed for all at 500ml&#47;min&#46; Interdialytic weight gain was 1&#46;8 &#177; 0&#46;75kg&#46;</p><p class="elsevierStylePara">Total mean conductivity was 13&#46;9 &#177; 0&#46;1ms&#47;cm and mean bicarbonate conductivity was 3&#46;1 &#177; 0&#46;1ms&#47;cm and both remained constant for all patients during the study&#46; The temperature of the DF was fixed at 36&#186; C for all patients in all the centres during the study&#46; All patients used high permeable synthetic membranes during the first three months of the study&#46; When the technique was changed to on-line PHF&#44; the membranes were substituted by double chamber polyethersulfone dialysers&#46; The mean volume of liquid infused during pre-dilution was 10L&#47;hour&#46;</p><p class="elsevierStylePara">All the patients underwent conventional HD for three months and one group was then randomised to on-line PHF technique using a conventional concentrate with bicarbonate for six months and then changed to on-line PHF with acetate-free concentrate &#40;611 free-acetate&#44; Bellco&#44; Mirandola&#44; Italy&#41;&#46; The other group reversed these two periods&#46; The patients were randomised by centre and allocation order&#46; Blood tests were performed monthly throughout the study&#46; Clinical data was collected during 13 consecutive sessions at baseline and at 3&#44; 6&#44; 9&#44; 12 and 15 months&#46;</p><p class="elsevierStylePara">The three techniques used during the study were performed using the Formula dialysis machine &#40;Bellco&#44; Mirandola&#44; Italy&#41;&#46;</p><p class="elsevierStylePara">HD tolerance was evaluated as in terms of number of hypotensive episodes&#44; headaches&#44; pruritus&#44; vomiting or cramps per month&#46;</p><p class="elsevierStylePara">Episodes of hypotension were defined as a fall in systolic blood pressure&#44; below 95mmHg associated with symptoms requiring the intervention of healthcare professionals&#46;</p><p class="elsevierStylePara">Monthly blood tests performed pre and post-HD included urea&#44; creatinine&#44; sodium&#44; potassium&#44; chloride&#44; bicarbonate&#44; acetate&#44; calcium&#44; phosphate&#44; glucose&#44; albumin&#44; &#946;2-microglobulin and C-reactive protein &#40;CRP&#41;&#46; The latter was analysed using nephelometry &#40;ultrasensitive CRP&#44; Behring Diagnostics&#44; GMBH&#44; Rarburg&#44; Germany&#41; with a detection limit of 0&#46;1mg&#47;ml and a reference range between 0&#46;1 and 0&#46;4mg&#47;L&#46; The coefficient of variation was lower than 4&#37;&#46;</p><p class="elsevierStylePara">The following were measured pre-dialysis&#58; uric acid&#44; total cholesterol&#44; HDL cholesterol&#44; triglyceride&#44; total proteins&#44; prealbumin&#44; ferritin&#44; transferrin saturation index&#44; serum iron&#44; parathyroid hormone&#44; haematocrit&#44; haemoglobin&#44; fibrinogen and homocysteine&#46;</p><p class="elsevierStylePara">Serum acetate was determined by the ultraviolet radiation method&#46; The enzymatic reaction in acetate synthesis results in the formation of NADH&#43; measured as an increase in absorbency&#46; Normal values in the healthy population were lower than 0&#46;1mmol&#47;L with a detection limit of 0&#46;01mmol&#47;L&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Preparing the acetate-free DF</span></p><p class="elsevierStylePara">All the electrolytes&#44; except from bicarbonate&#44; were present on the concentrate&#46;The acetic acid was substituted by HCl &#40;Bellco-Soludia&#44; Fourquevaux&#44; France&#41;&#46; The pH of the concentrate was then less than 1&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">The data are expressed as mean &#177; standard deviation&#46; The Kolmogorov-Smirnov test was used to evaluate the normal distribution of the variables&#46; All the variables had normal distribution with the exception of CRP which had an exponential curve and required logarithm transformation&#46; For parametric variables&#44; the paired t-test was used for two measurements and the ANOVA test for more than two&#46;</p><p class="elsevierStylePara">For non-parametric variables&#44; the Wilcoxon test was used for two measurements and the Dunett&#8217;s test for more than two&#46; The Friedman test was used to evaluate the effect of the different treatments on HD tolerance&#46;</p><p class="elsevierStylePara">The X<span class="elsevierStyleInf">2</span> test was used for categorical variables&#46; All the data were analysed using the SPSS version 12&#46; Statistical significance was defined as p &#60; 0&#46;05&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">The study lasted 15 months&#46;</p><p class="elsevierStylePara">Of the 35 patients 30 were randomised&#46; Of these four died&#44; five received a kidney transplant and 21 completed the study&#46;</p><p class="elsevierStylePara">During the first six months&#44; 12 patients were randomised to on-line PHF with conventional DF and 18 patients were randomised to on-line PHF with acetate-free DF&#46; The groups then switched to the alternative treatment for a further 6 months&#46;</p><p class="elsevierStylePara">No significant differences were found in the biochemical parameters&#44; except for post-dialysis chloride level and pre and post-dialysis bicarbonate&#46; Dry weight and interdialytic weight gain remained stable during the entire study &#40;table 2&#41;&#46;</p><p class="elsevierStylePara">The pre-dialysis plasma acetate levels during the conventional HD treatment period and the acetate-free on line PHF &#177; standard deviation of the concentrate did not differ statistically from the group treated with on-line PHF with HCl concentrate &#40;0&#46;10 &#177; 0&#46;09 vs&#46; 0&#46;09 &#177; 0&#46;07mmol&#47;L&#44; p &#61; ns&#41;&#44; while the post-dialysis acetate levels were significantly higher during the treatment period with acetic acid concentrate in comparison to the treatment with HC1 concentrate &#40;0&#46;24 &#177; 0&#46;16 vs&#46; 0&#46;15 &#177; 0&#46;13&#44; p &#61; 0&#44;000&#41; &#40;table 2&#41;&#46;</p><p class="elsevierStylePara">There were no significant differences in the nonphysiological values of acetate in pre-dialysis &#40;26&#37; of patients using DF with acetate&#44; 17&#37; of patients using DF with HC1&#44; p &#61; ns&#41;&#46; There were however significant differences between the two treatment periods &#40;with or without acetate&#41; regarding the presence of pathological values of acetate in post-dialysis &#40;61&#37; of patients using DF with acetate vs 30&#37; of patients using DF with HC1&#44; p &#61; 0&#46;000&#41; &#40;figure 1&#41;&#46;</p><p class="elsevierStylePara">On-line HDF with conventional DF was associated with fewer hypotensive episodes than treatment with conventional HD or on-line PHF without acetate &#40;p &#61; 0&#46;019&#41;&#44; &#40;figure 2&#41;&#46; There was no difference in the remaining parameters for dialysis tolerance between the groups but the symptoms&#160; were very low throughout the study&#46;</p><p class="elsevierStylePara">No significant differences were found in the &#946;2-microglobulin reduction rate between conventional HD and convective techniques &#40;table 2&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">With the widespread use of dialysis in patients with multiple co-morbidities &#40;diabetics&#44; advanced age&#44; cardiovascular complications&#41; there is a need for more efficient &#40;better clearance of larger uraemic toxins&#41; and well tolerated &#40;more biocompatible&#41; dialysis techniques&#46;</p><p class="elsevierStylePara">In recent years&#44; pre and post-dilution convective techniques and acetate-free techniques such as acetate-free biofiltration &#40;AFB&#41; led to an improvement in haemodynamic tolerance&#44; correction of the acid-base balance&#44; clearance of larger molecules and greater biocompatibility &#40;ultrapure water&#41; in comparison with conventional HD&#46;<span class="elsevierStyleSup">6&#44;11</span> The present study did not find greater clearance of &#946;2-microglobulin with convective treatment in comparison with conventional HD&#44; however this may be explained by insufficient volumes of pre-dilution reinfusate&#46;</p><p class="elsevierStylePara">When the study was performed&#44; the Formula machine did not allow infusion flows greater than 160ml&#47;min for on-line HDF&#46; This meant that the volume infused was limited to between 28&#46;8 and 38&#46;4L&#46; The comparable volume&#44; in terms of the clearance of medium molecules such as &#8218;&#946;2-microglobulin&#44; is 20L in post-dilution HDF&#44; which would be approximately 60L in pre-dilution HDF&#46;<span class="elsevierStyleSup">12</span></p><p class="elsevierStylePara">As expected&#44; the acetate-free on-line PHF allows the majority of patients to complete treatment with post-HD acetatemia within the physiological range in comparison with the other two techniques which use conventional concentrate with 4mmol&#47;L of acetate&#46; These results are in agreement with other studies&#44; whether using conventional HD and DF with or without acetate or pre-dilution HDF using DF with or without acetate&#46;<span class="elsevierStyleSup">4&#44;5&#44;13</span></p><p class="elsevierStylePara">Recently&#44; Pizzarelli <span class="elsevierStyleItalic">et al&#46;</span><span class="elsevierStyleSup">5</span> reported that the gain in acetate is particularly high in convective treatments and that the plasma levels of acetate return to baseline levels two hours after completing the treatment&#46; In our study&#44; we found no differences in the pre-dialysis values using the concentrate with or without acetate supporting the finding of temporary hyperacetatemia&#46;</p><p class="elsevierStylePara">In this study&#44; there was a reduction in the levels of bicarbonate&#44; pre and post-dialysis&#44; in patients using the acetate-free concentrate&#46; Once in the body&#44; the acetate converts to bicarbonate&#46; Thus&#44; in a patient with bicarbonate levels of 20mmol&#47;L in the plasma pre-dialysis&#44; who undergoes HD with a conventional DF&#44; containing 4mmol&#47;L of acetic acid&#44; in the final positive balance of buffer&#44; approximately 25&#37; corresponds to acetic acid and its metabolisation&#46; With the new acetate-free DF&#44; this component does not exist and therefore to achieve a similar balance the concentration of bicarbonate in the DF needs to be increased&#44; raising its partial conductivity&#46; We suggest that this needs to be increased by 0&#46;2mS&#47;cm&#44; as proposed by Pizzarelli <span class="elsevierStyleItalic">et al</span>&#46; in their study&#46;<span class="elsevierStyleSup">14</span></p><p class="elsevierStylePara">It is known that the acetate induces hypotension by causing vasodilatation and myocardial depression&#46; When we changed from a conventional HD to the convective technique using a standard concentrate&#44; the number of hypotensive episodes was reduced&#46; However it was surprising that when we used acetate-free on-line PHF technique the number of hypotensive episodes increased again &#40;as in the conventional HD treatment period&#41;&#46; One possible explanation for this phenomenon may be that the lower supply of bicarbonate in the acetate-free dialysate group was not compensated for by increasing the bicarbonate conductivity in the machine and&#44; therefore&#44; the tendency towards acidosis resulted in poorer tolerance in the convective technique&#46; In addition to this&#44; the concentration of sodium in the DF has a direct and significant influence on tolerance of dialysis&#46; The ratio between sodium concentration and final conductivity decreases due to the increased concentration of chloride in this new DF&#46; Chloride has a high ionic strenght which significantly contributes to conductivity&#44; with higher strenght than that of acetic acid&#46; Since the machine adjusts dilution based on final conductivity&#44; the increased chloride is compensated with greater dilution of the other elements&#44; with greater proportional influence on sodium&#46; To maintain sodium concentration in acetate-free DF we have to increase the total final conductivity by 0&#46;2mS&#47;cm&#46; It is important to remember that if these adjustments are not made&#44; the patient dialysing with the new acetate-free DF will be more acidotic and the dialysate will have less sodium&#46;</p><p class="elsevierStylePara">Among the multiple factors influencing anaemia in renal failure&#44; is the existence of molecules that accumulate during uraemia which inhibit erythropoiesis&#46;<span class="elsevierStyleSup">15</span> By clearing particles of greater molecular weight&#44; convective techniques allow better control of anaemia and a reduced dose of erythropoietin&#46;<span class="elsevierStyleSup">16 </span>In addition it is known that acetate is a promoter of inflammation and this in turn reduces the response to erythropoietin&#46; We did not find any changes in haemoglobin levels or erythropoietin requirements after changing from conventional HD to the convective technique with or without acetate&#46;</p><p class="elsevierStylePara">It has been suggested that the repeated increase in acetatemia during the dialysis sessions is part of the chronic inflammation presented by patients with renal failure in HD&#46; The exposure to small amounts of acetate during conventional HD is able to induce the production of cytokines by activated polymorphonuclear leukocytes&#44; demonstrated by increased TNF synthesis&#44; serum levels of IL-1&#8218; and nitric oxide synthetase activity&#46;<span class="elsevierStyleSup">17-19</span> The inflammatory parameters evaluated during the study&#44; such as CRP&#44; ferritin and&#47;or albumin&#44; were not modified following the change in technique and&#47;or dialysate&#46; The duration of the study and the small sample size &#40;21&#47;30 patients selected completed the study&#41; may have been insufficient to detect significant changes in these parameters&#46;</p><p class="elsevierStylePara">It is also to be noted that the sample of patients who participated in this study is not representative of the global HD population since&#44; by including patients with good vascular access allowing high blood flows&#44; a population with low prevalence of diabetes mellitus was selected and catheters for vascular access were excluded&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span></p><p class="elsevierStylePara">The on-line PHF technique using an acetate-free concentrate prevents exposure to high concentrations of acetate with the patient achieving the end of the HD session levels of acetatemia within the physiological range&#46; On-line PHF is a pre-dilution PHF treatment with greater tolerance than conventional HD using bicarbonate&#44; that requires high volumes of replacement liquid to achieve effective clearance of molecules with greater molecular weight such as &#946;2-microglobulin&#46; Improvement in tolerance of dialysis may be achieved by the addition of acetate-free DF&#44; but this should be accompanied by increased bicarbonate conductivity &#40;&#43;0&#46;2mS&#47;cm&#41; and total conductivity &#40;&#43;0&#46;2mS&#47;cm&#41; in the HD machine&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgement</span></p><p class="elsevierStylePara">To Sorin Group&#46;</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;t1a&#95;p157&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_t1a_p157.jpg" alt="Characteristics of the patients selected for the study"></img></a></p><p class="elsevierStylePara">Table 1a&#46; Characteristics of the patients selected for the study</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;t1b&#95;p158&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_t1b_p158.jpg" alt="Characteristics of the patients who completed the study"></img></a></p><p class="elsevierStylePara">Table 1b&#46; Characteristics of the patients who completed the study</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;t2&#95;p159&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_t2_p159.jpg" alt="Monitoring of different biochemical parameters pre and post-dialysis"></img></a></p><p class="elsevierStylePara">Table 2&#46; Monitoring of different biochemical parameters pre and post-dialysis</p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;f1&#95;p160&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_f1_p160.jpg"></img></a></p><p class="elsevierStylePara">Figure 1&#46; </p><p class="elsevierStylePara"><a href="grande&#47;20718078&#95;f2&#95;p160&#46;jpg" class="elsevierStyleCrossRefs"><img src="20718078_f2_p160.jpg"></img></a></p><p class="elsevierStylePara">Figure 2&#46; </p>"
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            0 => "PHF on-line"
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            0 => "Hemodi&#225;lisis"
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          "clase" => "keyword"
          "titulo" => "Keywords"
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          "clase" => "keyword"
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          "clase" => "keyword"
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        "resumen" => "<p class="elsevierStylePara">Antecedentes&#58; la presencia de ac&#233;tico en el L&#237;quido de Di&#225;lisis &#40;LD&#41; expone al paciente a una concentraci&#243;n de acetato 30-40 veces superior a la normal&#46; Dicha exposici&#243;n aumenta en t&#233;cnicas de Hemodiafiltraci&#243;n &#40;HDF&#41; online&#46; El objetivo de dicho estudio fue evaluar los cambios cl&#237;nico-anal&#237;ticos al usar tres t&#233;cnicas de Hemodi&#225;lisis &#40;HD&#41; diferentes&#46; M&#233;todos&#58; se reclutaron 35 pacientes en HD estable&#46; Se dializaron tres meses con HD convencional y luego fueron aleatorizados para pasar a una t&#233;cnica de PHF on-line con concentrado convencional seis meses&#44; y despu&#233;s pasaron a PHF on-line sin acetato otros seis meses&#46; El otro grupo invert&#237;a estos dos per&#237;odos&#46; Se obtuvieron an&#225;lisis de sangre y datos cl&#237;nicos de HD&#46; Resultados&#58; las medias de los acetatos posdi&#225;lisis fueron significativamente superiores durante los per&#237;odos de tratamiento con ac&#233;tico respecto al per&#237;odo sin acetato&#46; El porcentaje de valores patol&#243;gicos de acetato posdi&#225;lisis fue significativamente superior durante los per&#237;odos de tratamiento con ac&#233;tico &#40;61 respecto al 30&#37;&#41;&#46; Las concentraciones de cloro pos-HD fueron superiores y las de bicarbonato pre y pos-HD fueron menores durante el per&#237;odo sin ac&#233;tico&#46; El n&#250;mero de hipotensiones fue significativamente inferior en el per&#237;odo de PHF on-line con LD est&#225;ndar respecto a los otros per&#237;odos&#46; Conclusiones&#58; la t&#233;cnica de PHF on-line sin acetato disminuye la exposici&#243;n a concentraciones elevadas de acetato y consigue que la mayor&#237;a de pacientes termine la HD con una acetatemia en el rango fisiol&#243;gico&#46; La PHF on-line es un tratamiento de HDF predilucional con mejor tolerancia que la HD est&#225;ndar con bicarbonato&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">Summary Background&#58; the small quantity of acetate present in the dialysis fluid exposes patient&#8217;s blood to an acetate concentration 30-40 times the physiological levels&#46; This amount is even greater in hemodiafiltration on-line&#46; Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient&#46; Methods&#58; 35 patients on hemodialysis were included&#46; All patients were treated with conventional bicarbonate dialysate for 3 months&#44; after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods&#46; Blood samples were drawn monthly throughout the study and clinical data were obtained&#46; Results&#58; Posdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate&#46; Moreover&#44; the percentage of patients with posdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period &#40;61&#37; vs&#46; 30&#37;&#41;&#46; Serum concentrations of chloride posdialysis were higher and serum concentrations of bicarbonate pre and poshemodialysis were lower in the PHF free-acetate period&#46; The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate&#46; Conclusions&#58; PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges&#46; PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate&#46;</p>"
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