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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">In the history of haemodialysis there are examples of technical advances that replaced existing procedures&#46; Volumetric ultrafiltration control&#44; the use of bicarbonate in dialysis fluid and synthetic membranes gave rise to the abandonment of pressure gradient ultrafiltration systems&#44; acetate baths and cellulose membranes&#46; The criteria that justified the changes were not always the same&#58; the technical innovations in the first two cases were not established due to scientific evidence provided by research&#44; but because clinical experience confirmed that ultrafiltration provided more accurate volumetric control and the bicarbonate bath allowed greater tolerance to the dialysis session&#46; On the other hand&#44; the gradual abandonment of cellulose membranes was a consequence of the research which demonstrated that synthetic membranes brought about a less significant inflammatory reaction and had a positive effect on the incidence and severity of amyloidosis due to beta-2-microglobulin amyloid deposit&#46; We are currently experiencing a boom in dialysis techniques in which the convection principle is dominant over diffusion&#46; The debate that has arisen is whether the time has come to replace traditional haemodialysis with convective procedures&#46;</p><p class="elsevierStylePara">The use of convection instead of diffusion as the main mechanism of renal clearance is not currently being proposed&#46; The pure convective technique &#40;haemofiltration&#41; is a procedure as long-standing as haemodialysis&#46; Subsequently&#44; various different convective techniques emerged &#40;haemodiafiltration&#44; biofiltration&#44; PFD&#44; AFB&#41;&#46; None of these managed to represent a true alternative to conventional treatment&#44; due to their complexity&#44; greater cost and a lack of results that demonstrated a clear clinical advantage&#46; The production of a sterile dialysis fluid &#40;ultrapure fluid&#41; which could be used as intravenous replacement fluid in convective techniques &#40;&#191;on-line&#191; convection&#41; was the great technical advance which resolved&#44; in part&#44; the previous disadvantages and renewed interest in these procedures&#46; &#191;On-line&#191; convection allows large ultrafiltration volumes to be obtained via simple methods and at a significantly lower cost&#46;</p><p class="elsevierStylePara">Of the various convective techniques which included dialysis bath infusion&#44; &#191;on-line&#191; haemodiafiltration has acquired a greater relevance due to both its gradual expansion and the number of scientific publications to which it has given rise&#46; Recent general reviews and editorial commentaries confirm that &#191;on-line&#191; haemodiafiltration is a safe technique&#44; which provides increased clearance efficacy and improved clinical results at a cost not much higher than haemodialysis&#46;<span class="elsevierStyleSup">1-9</span></p><p class="elsevierStylePara">A recent survey carried out among dialysis professionals indicates that according to European nephrologists&#44; &#191;on-line&#191; haemodiafiltration is the best dialysis procedure currently in existence&#46;<span class="elsevierStyleSup">10</span></p><p class="elsevierStylePara">On the basis of data obtained from published studies&#44; is there sufficient criteria to propose the replacement of haemodialysis by convective techniques&#44; particularly by &#191;online&#191; haemodiafiltration as the most representative form&#63;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">METHODOLOGICAL PROBLEMS IN COMPARATIVE STUDIES</span></p><p class="elsevierStylePara">Many of the studies relating to convective techniques have methodological aspects which must be borne in mind when evaluating the results&#46;</p><p class="elsevierStylePara">&#191;On-line&#191; convective techniques use a high flux biocompatible membrane and an ultrapure dialysis bath&#46; The biocompatibility and permeability of the membrane have a determining influence on the plasma concentration of beta-2-microglobulin&#44;<span class="elsevierStyleSup">11-16</span> on the triggering of inflammatory phenomena induced by dialysis<span class="elsevierStyleSup">15&#44;17-20</span> and on the onset of clinical complications due to amyloidosis of the patient under dialysis&#46;<span class="elsevierStyleSup">21-27</span> Their possible beneficial effects on anaemia&#44; nutrition and mortality are under debate&#46;<span class="elsevierStyleSup">12&#44;14&#44;15&#44;25&#44;28-34</span></p><p class="elsevierStylePara">The ultrapure dialysis bath has been related with favourable&#47;beneficial effects on anaemia<span class="elsevierStyleSup">35-41</span> nutrition&#44;<span class="elsevierStyleSup">35&#44;40&#44;42&#44;43</span> inflammation&#44;<span class="elsevierStyleSup">36&#44;38-42&#44;44&#44;45</span> oxidative stress&#44;<span class="elsevierStyleSup">45&#44;46</span> reduction in the levels of beta-2-microglobulin&#44;<span class="elsevierStyleSup">38&#44;43&#44;45</span> prevalence of amyloidosis related with dialysis&#44;<span class="elsevierStyleSup">26&#44;47&#44;48</span> and cardiovascular morbidity&#46;<span class="elsevierStyleSup">44</span> Many of these beneficial effects are described in patients treated with convective techniques and it is difficult to determine if they should be attributed to the quality of the membrane&#44; the purity of the dialysis bath or convection itself&#46; In order to be able to evaluate the influence of convection&#44; the haemodialysis technique with which it is being compared should be carried out in identical conditions of quality of bath and membrane&#46; Indeed&#44; an equal surface area of the dialysis machine&#44; arterial flow and dialysis bath fluid flow are also necessary&#46;</p><p class="elsevierStylePara">Another aspect that must be borne in mind is the lack of a control group in many observational studies&#44; especially those which analyse the data before and after the change of technique&#46; The improvement of results due to the &#191;test effect&#191; is a bias which must be borne in mind in this type of study&#46; There are two examples showing the importance of the control group&#58; Locatelli&#191;s study on membrane permeability and anaemia<span class="elsevierStyleSup">14</span> and Ward&#191;s study on haemodiafiltration and serum beta 2-microglobulin concentration&#46;<span class="elsevierStyleSup">49</span> The conclusions of both studies would have been completely different if a control group had not been used&#46;</p><p class="elsevierStylePara">Finally&#44; it must be stressed that the results of nonrandomised studies must be analysed with caution&#46; The convective technique&#44; especially in postdilution form&#44; requires an adequate blood flow&#44; which conditions the selection criteria for patients&#46; The fact that it is an alternative to the usual treatment means that this procedure is not usually used on patients for whom a poor prognosis is expected in the short term&#46; This is particularly the case for the initial periods during which health care professionals are attempting to acquire experience with this technique&#46; The selection bias&#44; determined by vascular access and expected prognosis is inherent to any non-randomised study&#46;</p><p class="elsevierStylePara">Despite all of the aforementioned limitations&#44; can we be certain that the clinical results obtained with &#191;on-line&#191; convective techniques are clearly superior to those achieved with haemodialysis&#44; based on existing publications&#63;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS OF STUDIES ON CONVECTION</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Systematic reviews</span></p><p class="elsevierStylePara">Two systematic reviews that analyse this subject have been published&#46; The review by Rabindranath et al only includes randomised&#44; controlled studies&#59; initially&#44; 18 studies with 588 patients<span class="elsevierStyleSup">50</span> were analysed&#59; this was subsequently extended to 20 studies with 657 patients&#46;<span class="elsevierStyleSup">51</span> The review by Varela and Ruano includes&#44; in addition&#44; observational cohort studies&#44; but excludes all studies with less than 20 patients&#59; the paragraph relating to convective techniques is an analysis of the data of 17 studies&#44; seven of which are also included in the review by Rabindranath et al&#44; with a total of 1&#44;489 patients&#46;<span class="elsevierStyleSup">52</span> The authors of both systematic reviews conclude that it is not possible to demonstrate that the convective techniques provide advantages in relevant clinical aspects such as mortality&#44; morbidity&#44; tolerance to dialysis or quality of life&#46; They also highlight the methodological shortcomings of many studies and the need to undertake higher quality clinical tests&#44; in order to reach definitive conclusions&#46;</p><p class="elsevierStylePara">We shall summarise below the most significant data&#44; including subsequent publications and aspects that have not been considered in the two previous systematic reviews&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Mortality</span></p><p class="elsevierStylePara">Two new randomised&#44; controlled clinical tests analyse mortality&#46; In the first test&#44; no difference was observed between &#191;on-line&#191; haemodiafiltration and high-flux haemodialysis&#46;<span class="elsevierStyleSup">53</span> The second test confirms a higher survival rate in the group treated with &#191;on-line&#191; haemofiltration with regard to the group treated with lowflux haemodialysis&#59;<span class="elsevierStyleSup">54</span> both the authors themselves and the corresponding editorial commentary<span class="elsevierStyleSup">55</span> recognise the limitations of the study due to the small number of patients and the high abandonment rate&#46;</p><p class="elsevierStylePara">The influence of the convective technique on mortality has been the subject of analysis in four observational studies undertaken using various patient records&#46;<span class="elsevierStyleSup">56-59</span> While in the first test there were no statistically significant differences&#44; in the other three studies&#44; mortality was lower in the group treated with &#191;on-line&#191; haemodiafiltration&#46; The data on mortality of these non-randomised observational studies must be analysed with caution due to the aforementioned selection bias&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Results of the clinical and analytical data</span></p><p class="elsevierStylePara">The conclusions of 47 comparative studies are shown in Table 1&#46; On analysis of the characteristics of the haemodialysis technique&#44; it must be emphasised that in 21 studies&#44; the membrane was low flux&#59; in 17 the dialysis machine had a lower surface area&#59; in eight the arterial flow was lower and in 19 the dialysis bath was not ultrapure&#46; Only in 12 studies these four parameters were similar with both techniques&#46; Sixteen of these studies corresponded to observational studies in which the effects of the change in technique were analysed&#44; without a control group&#46; Despite these methodological limitations which represent a bias in favour of convective techniques&#44; the results did not demonstrate a clear advantage over haemodialysis in the majority of the analysed parameters&#46;</p><p class="elsevierStylePara">Initial studies presented a higher haemodynamic tolerance&#59; it was subsequently demonstrated that it was due to a greater loss of heat induced by convection&#59; no differences were observed when compared with cold haemodialysis or with temperature biocontrol&#46;<span class="elsevierStyleSup">70-72&#44;76</span></p><p class="elsevierStylePara">Further data in favour of convection is found in studies relating to the behaviour of various markers of inflammation and oxidation&#44; whose clinical significance is still to be determined&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dialysis efficacy</span></p><p class="elsevierStylePara">Convective techniques do not provide a relevant increase in the elimination of small molecules with regard to haemodialysis&#44; provided that the rest of the variables which play a part in their clearance remain constant&#46;<span class="elsevierStyleSup">102&#44;103</span> Convection is more effective in the elimination of medium and large molecules&#46; Its higher clearance capacity&#44; reflected in the clearance rates or reduction of plasma concentration following treatment&#44; has been shown with numerous molecules&#44;<span class="elsevierStyleSup">49&#44;69&#44;103-107</span> but is not always accompanied by a reduction in the blood concentrations&#46;</p><p class="elsevierStylePara">The most studied molecule is beta-2-microglobulin&#46; Recent publications have shown a relationship between its plasma concentration and mortality&#46;<span class="elsevierStyleSup">108-110</span> The results of 24 studies allowing the analysis of beta-2-microglobulin concentration with different convective techniques are shown in Table 2&#46; It can be confirmed that in the majority of studies there are no differences with haemodialysis carried out with a high flux membrane&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Safety</span></p><p class="elsevierStylePara">The safety of convective techniques seems to be confirmed by the lack of studies that describe worse clinical results with these techniques&#46; However&#44; there are some aspects to be borne in mind&#46;</p><p class="elsevierStylePara">The loss of proteins and amino acids is greater&#46;<span class="elsevierStyleSup">118-121</span> The data of 23 studies in which the development of the plasma concentration of albumin following the start of convective treatment may be observed&#44; is shown in Table 3&#46; The general trend is a slight reduction in the concentration of albumin&#46;</p><p class="elsevierStylePara">There is some uncertainty regarding the safety of the technique and its consequences in the long term due to direct infusion of the dialysis bath fluid into the bloodstream&#46; Ultrapure water contains a wide variety of trace elements<span class="elsevierStyleSup">125</span> which&#44; once infused into the blood&#44; bind to plasma proteins and are difficult to eliminate&#46; The possible effect of its progressive accumulation remains to be established&#46; <span class="elsevierStyleSup">126&#44;127</span> Furthermore&#44; it is essential to guarantee the sterility of the infused solution&#46; The contamination of the endotoxin filter or&#44; subsequently&#44; of the hydraulic circuit would result in the infusion of a non-sterile bath fluid until the filter was changed or the regular endotoxin tests were carried out&#46; In addition&#44; it must be borne in mind that the dialysis bath fluid may contain other products of bacterial contamination which are not detected with the endotoxin tests&#44;<span class="elsevierStyleSup">128&#44;129</span> which pass through the protection filters<span class="elsevierStyleSup">130&#44;131</span> and which are capable of inducing and maintaining the in vitro inflammatory response&#46;<span class="elsevierStyleSup">130&#44;132</span> This bacterial residue is transferred directly into the bloodstream during &#191;on-line&#191; convective techniques&#44; although until now it has not been confirmed that they are capable of causing an in vivo inflammatory response&#46;</p><p class="elsevierStylePara">It is possible that haemodialysis with high flux dialysis machines involves a phenomenon of retrofiltration and that both the trace elements in the dialysis bath and the possible bacterial residue may reach the blood compartment&#46; However&#44; it must be borne in mind that the coating of the dialysis machine membrane by blood proteins represents a limit to the transfer of contaminating products from the dialysis bath through the dialysis machine&#46;<span class="elsevierStyleSup">133-135</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">CLINICAL CASES IN PROGRESS</span></p><p class="elsevierStylePara">In order to clarify some of these matters&#44; five randomised&#44; controlled clinical tests are being carried out&#44; which compare the results of &#191;on-line&#191; haemodiafiltration with conventional haemodialysis &#40;Table 4&#41;&#46; It is noteworthy that in two of the studies the membrane used in conventional haemodialysis is of low permeability&#46; The results of these studies will help clarify aspects currently under debate&#46; At present&#44; only the recently published data of one of the studies is known &#40;the CONTRAST Study&#41;&#58; &#191;on-line&#191; haemodiafiltration brings about a more intense and prolonged platelet activation than haemodialysis&#59; the clinical significance of this discovery is still to be established&#46;<span class="elsevierStyleSup">141</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span></p><p class="elsevierStylePara">We can conclude that the dialysis techniques based on convection are procedures with interesting aspects&#44; but&#44; until now&#44; its clear clinical superiority over haemodialysis with a high-permeability biocompatible membrane and ultrapure fluid has not been demonstrated&#46; Its safety is guaranteed by the lack of publications which show worse results&#44; although there are some issues which remain to be clarified&#46; Until the results of the clinical tests that are currently underway are published&#44; convective techniques will have to be used according to individual experience or if its use is desired&#44; and the facilities of each centre&#46; The time for change has not yet come&#46;<br></br></p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t1&#95;p596&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t1_p596.jpg" alt="Comparative studies between convective techniques and haemodialysis"></img></a></p><p class="elsevierStylePara">Table 1&#46; Comparative studies between convective techniques and haemodialysis</p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t2&#95;p597&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t2_p597.jpg" alt="Influence of the convective technique on the plasma concentration of beta-2-microglobulin"></img></a></p><p class="elsevierStylePara">Table 2&#46; Influence of the convective technique on the plasma concentration of beta-2-microglobulin</p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t3&#95;p597&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t3_p597.jpg" alt="Development of the concentration of albumin following the initiation of convective treatment"></img></a></p><p class="elsevierStylePara">Table 3&#46; Development of the concentration of albumin following the initiation of convective treatment</p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t4&#95;p598&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t4_p598.jpg" alt="Clinical tests with &#191;on-line&#191; haemodiafiltration in progress"></img></a></p><p class="elsevierStylePara">Table 4&#46; Clinical tests with &#191;on-line&#191; haemodiafiltration in progress</p>"
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Convection versus diffusion: Is it time to make the change?
Convección versus difusión: ¿ha llegado el momento del cambio?
José Luis Teruel Brionesa
a Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Madrid, España,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">In the history of haemodialysis there are examples of technical advances that replaced existing procedures&#46; Volumetric ultrafiltration control&#44; the use of bicarbonate in dialysis fluid and synthetic membranes gave rise to the abandonment of pressure gradient ultrafiltration systems&#44; acetate baths and cellulose membranes&#46; The criteria that justified the changes were not always the same&#58; the technical innovations in the first two cases were not established due to scientific evidence provided by research&#44; but because clinical experience confirmed that ultrafiltration provided more accurate volumetric control and the bicarbonate bath allowed greater tolerance to the dialysis session&#46; On the other hand&#44; the gradual abandonment of cellulose membranes was a consequence of the research which demonstrated that synthetic membranes brought about a less significant inflammatory reaction and had a positive effect on the incidence and severity of amyloidosis due to beta-2-microglobulin amyloid deposit&#46; We are currently experiencing a boom in dialysis techniques in which the convection principle is dominant over diffusion&#46; The debate that has arisen is whether the time has come to replace traditional haemodialysis with convective procedures&#46;</p><p class="elsevierStylePara">The use of convection instead of diffusion as the main mechanism of renal clearance is not currently being proposed&#46; The pure convective technique &#40;haemofiltration&#41; is a procedure as long-standing as haemodialysis&#46; Subsequently&#44; various different convective techniques emerged &#40;haemodiafiltration&#44; biofiltration&#44; PFD&#44; AFB&#41;&#46; None of these managed to represent a true alternative to conventional treatment&#44; due to their complexity&#44; greater cost and a lack of results that demonstrated a clear clinical advantage&#46; The production of a sterile dialysis fluid &#40;ultrapure fluid&#41; which could be used as intravenous replacement fluid in convective techniques &#40;&#191;on-line&#191; convection&#41; was the great technical advance which resolved&#44; in part&#44; the previous disadvantages and renewed interest in these procedures&#46; &#191;On-line&#191; convection allows large ultrafiltration volumes to be obtained via simple methods and at a significantly lower cost&#46;</p><p class="elsevierStylePara">Of the various convective techniques which included dialysis bath infusion&#44; &#191;on-line&#191; haemodiafiltration has acquired a greater relevance due to both its gradual expansion and the number of scientific publications to which it has given rise&#46; Recent general reviews and editorial commentaries confirm that &#191;on-line&#191; haemodiafiltration is a safe technique&#44; which provides increased clearance efficacy and improved clinical results at a cost not much higher than haemodialysis&#46;<span class="elsevierStyleSup">1-9</span></p><p class="elsevierStylePara">A recent survey carried out among dialysis professionals indicates that according to European nephrologists&#44; &#191;on-line&#191; haemodiafiltration is the best dialysis procedure currently in existence&#46;<span class="elsevierStyleSup">10</span></p><p class="elsevierStylePara">On the basis of data obtained from published studies&#44; is there sufficient criteria to propose the replacement of haemodialysis by convective techniques&#44; particularly by &#191;online&#191; haemodiafiltration as the most representative form&#63;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">METHODOLOGICAL PROBLEMS IN COMPARATIVE STUDIES</span></p><p class="elsevierStylePara">Many of the studies relating to convective techniques have methodological aspects which must be borne in mind when evaluating the results&#46;</p><p class="elsevierStylePara">&#191;On-line&#191; convective techniques use a high flux biocompatible membrane and an ultrapure dialysis bath&#46; The biocompatibility and permeability of the membrane have a determining influence on the plasma concentration of beta-2-microglobulin&#44;<span class="elsevierStyleSup">11-16</span> on the triggering of inflammatory phenomena induced by dialysis<span class="elsevierStyleSup">15&#44;17-20</span> and on the onset of clinical complications due to amyloidosis of the patient under dialysis&#46;<span class="elsevierStyleSup">21-27</span> Their possible beneficial effects on anaemia&#44; nutrition and mortality are under debate&#46;<span class="elsevierStyleSup">12&#44;14&#44;15&#44;25&#44;28-34</span></p><p class="elsevierStylePara">The ultrapure dialysis bath has been related with favourable&#47;beneficial effects on anaemia<span class="elsevierStyleSup">35-41</span> nutrition&#44;<span class="elsevierStyleSup">35&#44;40&#44;42&#44;43</span> inflammation&#44;<span class="elsevierStyleSup">36&#44;38-42&#44;44&#44;45</span> oxidative stress&#44;<span class="elsevierStyleSup">45&#44;46</span> reduction in the levels of beta-2-microglobulin&#44;<span class="elsevierStyleSup">38&#44;43&#44;45</span> prevalence of amyloidosis related with dialysis&#44;<span class="elsevierStyleSup">26&#44;47&#44;48</span> and cardiovascular morbidity&#46;<span class="elsevierStyleSup">44</span> Many of these beneficial effects are described in patients treated with convective techniques and it is difficult to determine if they should be attributed to the quality of the membrane&#44; the purity of the dialysis bath or convection itself&#46; In order to be able to evaluate the influence of convection&#44; the haemodialysis technique with which it is being compared should be carried out in identical conditions of quality of bath and membrane&#46; Indeed&#44; an equal surface area of the dialysis machine&#44; arterial flow and dialysis bath fluid flow are also necessary&#46;</p><p class="elsevierStylePara">Another aspect that must be borne in mind is the lack of a control group in many observational studies&#44; especially those which analyse the data before and after the change of technique&#46; The improvement of results due to the &#191;test effect&#191; is a bias which must be borne in mind in this type of study&#46; There are two examples showing the importance of the control group&#58; Locatelli&#191;s study on membrane permeability and anaemia<span class="elsevierStyleSup">14</span> and Ward&#191;s study on haemodiafiltration and serum beta 2-microglobulin concentration&#46;<span class="elsevierStyleSup">49</span> The conclusions of both studies would have been completely different if a control group had not been used&#46;</p><p class="elsevierStylePara">Finally&#44; it must be stressed that the results of nonrandomised studies must be analysed with caution&#46; The convective technique&#44; especially in postdilution form&#44; requires an adequate blood flow&#44; which conditions the selection criteria for patients&#46; The fact that it is an alternative to the usual treatment means that this procedure is not usually used on patients for whom a poor prognosis is expected in the short term&#46; This is particularly the case for the initial periods during which health care professionals are attempting to acquire experience with this technique&#46; The selection bias&#44; determined by vascular access and expected prognosis is inherent to any non-randomised study&#46;</p><p class="elsevierStylePara">Despite all of the aforementioned limitations&#44; can we be certain that the clinical results obtained with &#191;on-line&#191; convective techniques are clearly superior to those achieved with haemodialysis&#44; based on existing publications&#63;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS OF STUDIES ON CONVECTION</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Systematic reviews</span></p><p class="elsevierStylePara">Two systematic reviews that analyse this subject have been published&#46; The review by Rabindranath et al only includes randomised&#44; controlled studies&#59; initially&#44; 18 studies with 588 patients<span class="elsevierStyleSup">50</span> were analysed&#59; this was subsequently extended to 20 studies with 657 patients&#46;<span class="elsevierStyleSup">51</span> The review by Varela and Ruano includes&#44; in addition&#44; observational cohort studies&#44; but excludes all studies with less than 20 patients&#59; the paragraph relating to convective techniques is an analysis of the data of 17 studies&#44; seven of which are also included in the review by Rabindranath et al&#44; with a total of 1&#44;489 patients&#46;<span class="elsevierStyleSup">52</span> The authors of both systematic reviews conclude that it is not possible to demonstrate that the convective techniques provide advantages in relevant clinical aspects such as mortality&#44; morbidity&#44; tolerance to dialysis or quality of life&#46; They also highlight the methodological shortcomings of many studies and the need to undertake higher quality clinical tests&#44; in order to reach definitive conclusions&#46;</p><p class="elsevierStylePara">We shall summarise below the most significant data&#44; including subsequent publications and aspects that have not been considered in the two previous systematic reviews&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Mortality</span></p><p class="elsevierStylePara">Two new randomised&#44; controlled clinical tests analyse mortality&#46; In the first test&#44; no difference was observed between &#191;on-line&#191; haemodiafiltration and high-flux haemodialysis&#46;<span class="elsevierStyleSup">53</span> The second test confirms a higher survival rate in the group treated with &#191;on-line&#191; haemofiltration with regard to the group treated with lowflux haemodialysis&#59;<span class="elsevierStyleSup">54</span> both the authors themselves and the corresponding editorial commentary<span class="elsevierStyleSup">55</span> recognise the limitations of the study due to the small number of patients and the high abandonment rate&#46;</p><p class="elsevierStylePara">The influence of the convective technique on mortality has been the subject of analysis in four observational studies undertaken using various patient records&#46;<span class="elsevierStyleSup">56-59</span> While in the first test there were no statistically significant differences&#44; in the other three studies&#44; mortality was lower in the group treated with &#191;on-line&#191; haemodiafiltration&#46; The data on mortality of these non-randomised observational studies must be analysed with caution due to the aforementioned selection bias&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Results of the clinical and analytical data</span></p><p class="elsevierStylePara">The conclusions of 47 comparative studies are shown in Table 1&#46; On analysis of the characteristics of the haemodialysis technique&#44; it must be emphasised that in 21 studies&#44; the membrane was low flux&#59; in 17 the dialysis machine had a lower surface area&#59; in eight the arterial flow was lower and in 19 the dialysis bath was not ultrapure&#46; Only in 12 studies these four parameters were similar with both techniques&#46; Sixteen of these studies corresponded to observational studies in which the effects of the change in technique were analysed&#44; without a control group&#46; Despite these methodological limitations which represent a bias in favour of convective techniques&#44; the results did not demonstrate a clear advantage over haemodialysis in the majority of the analysed parameters&#46;</p><p class="elsevierStylePara">Initial studies presented a higher haemodynamic tolerance&#59; it was subsequently demonstrated that it was due to a greater loss of heat induced by convection&#59; no differences were observed when compared with cold haemodialysis or with temperature biocontrol&#46;<span class="elsevierStyleSup">70-72&#44;76</span></p><p class="elsevierStylePara">Further data in favour of convection is found in studies relating to the behaviour of various markers of inflammation and oxidation&#44; whose clinical significance is still to be determined&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dialysis efficacy</span></p><p class="elsevierStylePara">Convective techniques do not provide a relevant increase in the elimination of small molecules with regard to haemodialysis&#44; provided that the rest of the variables which play a part in their clearance remain constant&#46;<span class="elsevierStyleSup">102&#44;103</span> Convection is more effective in the elimination of medium and large molecules&#46; Its higher clearance capacity&#44; reflected in the clearance rates or reduction of plasma concentration following treatment&#44; has been shown with numerous molecules&#44;<span class="elsevierStyleSup">49&#44;69&#44;103-107</span> but is not always accompanied by a reduction in the blood concentrations&#46;</p><p class="elsevierStylePara">The most studied molecule is beta-2-microglobulin&#46; Recent publications have shown a relationship between its plasma concentration and mortality&#46;<span class="elsevierStyleSup">108-110</span> The results of 24 studies allowing the analysis of beta-2-microglobulin concentration with different convective techniques are shown in Table 2&#46; It can be confirmed that in the majority of studies there are no differences with haemodialysis carried out with a high flux membrane&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Safety</span></p><p class="elsevierStylePara">The safety of convective techniques seems to be confirmed by the lack of studies that describe worse clinical results with these techniques&#46; However&#44; there are some aspects to be borne in mind&#46;</p><p class="elsevierStylePara">The loss of proteins and amino acids is greater&#46;<span class="elsevierStyleSup">118-121</span> The data of 23 studies in which the development of the plasma concentration of albumin following the start of convective treatment may be observed&#44; is shown in Table 3&#46; The general trend is a slight reduction in the concentration of albumin&#46;</p><p class="elsevierStylePara">There is some uncertainty regarding the safety of the technique and its consequences in the long term due to direct infusion of the dialysis bath fluid into the bloodstream&#46; Ultrapure water contains a wide variety of trace elements<span class="elsevierStyleSup">125</span> which&#44; once infused into the blood&#44; bind to plasma proteins and are difficult to eliminate&#46; The possible effect of its progressive accumulation remains to be established&#46; <span class="elsevierStyleSup">126&#44;127</span> Furthermore&#44; it is essential to guarantee the sterility of the infused solution&#46; The contamination of the endotoxin filter or&#44; subsequently&#44; of the hydraulic circuit would result in the infusion of a non-sterile bath fluid until the filter was changed or the regular endotoxin tests were carried out&#46; In addition&#44; it must be borne in mind that the dialysis bath fluid may contain other products of bacterial contamination which are not detected with the endotoxin tests&#44;<span class="elsevierStyleSup">128&#44;129</span> which pass through the protection filters<span class="elsevierStyleSup">130&#44;131</span> and which are capable of inducing and maintaining the in vitro inflammatory response&#46;<span class="elsevierStyleSup">130&#44;132</span> This bacterial residue is transferred directly into the bloodstream during &#191;on-line&#191; convective techniques&#44; although until now it has not been confirmed that they are capable of causing an in vivo inflammatory response&#46;</p><p class="elsevierStylePara">It is possible that haemodialysis with high flux dialysis machines involves a phenomenon of retrofiltration and that both the trace elements in the dialysis bath and the possible bacterial residue may reach the blood compartment&#46; However&#44; it must be borne in mind that the coating of the dialysis machine membrane by blood proteins represents a limit to the transfer of contaminating products from the dialysis bath through the dialysis machine&#46;<span class="elsevierStyleSup">133-135</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">CLINICAL CASES IN PROGRESS</span></p><p class="elsevierStylePara">In order to clarify some of these matters&#44; five randomised&#44; controlled clinical tests are being carried out&#44; which compare the results of &#191;on-line&#191; haemodiafiltration with conventional haemodialysis &#40;Table 4&#41;&#46; It is noteworthy that in two of the studies the membrane used in conventional haemodialysis is of low permeability&#46; The results of these studies will help clarify aspects currently under debate&#46; At present&#44; only the recently published data of one of the studies is known &#40;the CONTRAST Study&#41;&#58; &#191;on-line&#191; haemodiafiltration brings about a more intense and prolonged platelet activation than haemodialysis&#59; the clinical significance of this discovery is still to be established&#46;<span class="elsevierStyleSup">141</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span></p><p class="elsevierStylePara">We can conclude that the dialysis techniques based on convection are procedures with interesting aspects&#44; but&#44; until now&#44; its clear clinical superiority over haemodialysis with a high-permeability biocompatible membrane and ultrapure fluid has not been demonstrated&#46; Its safety is guaranteed by the lack of publications which show worse results&#44; although there are some issues which remain to be clarified&#46; Until the results of the clinical tests that are currently underway are published&#44; convective techniques will have to be used according to individual experience or if its use is desired&#44; and the facilities of each centre&#46; The time for change has not yet come&#46;<br></br></p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t1&#95;p596&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t1_p596.jpg" alt="Comparative studies between convective techniques and haemodialysis"></img></a></p><p class="elsevierStylePara">Table 1&#46; Comparative studies between convective techniques and haemodialysis</p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t2&#95;p597&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t2_p597.jpg" alt="Influence of the convective technique on the plasma concentration of beta-2-microglobulin"></img></a></p><p class="elsevierStylePara">Table 2&#46; Influence of the convective technique on the plasma concentration of beta-2-microglobulin</p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t3&#95;p597&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t3_p597.jpg" alt="Development of the concentration of albumin following the initiation of convective treatment"></img></a></p><p class="elsevierStylePara">Table 3&#46; Development of the concentration of albumin following the initiation of convective treatment</p><p class="elsevierStylePara"><a href="grande&#47;44418078&#95;t4&#95;p598&#46;jpg" class="elsevierStyleCrossRefs"><img src="44418078_t4_p598.jpg" alt="Clinical tests with &#191;on-line&#191; haemodiafiltration in progress"></img></a></p><p class="elsevierStylePara">Table 4&#46; Clinical tests with &#191;on-line&#191; haemodiafiltration in progress</p>"
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Nefrología (English Edition)