Impact of hemodialysis duration on the removal of uremic retention solutes
2007; Elsevier BV; Volume: 73; Issue: 6 Linguagem: Inglês
10.1038/sj.ki.5002750
ISSN1523-1755
AutoresSunny Eloot, Wim Van Biesen, Annemieke Dhondt, H. Van de Wynkele, Griet Glorieux, P. Verdonck, Raymond Vanholder,
Tópico(s)Central Venous Catheters and Hemodialysis
ResumoSeveral studies have stressed the importance of dialysis time in the removal of uremic retention solutes. To further investigate this, nine stable chronic hemodialysis patients were dialyzed for 4, 6, or 8 h processing the same total blood and dialysate volume by the Genius system and high-flux FX80 dialyzers. Inlet blood and outlet dialysate were analyzed for urea, creatinine, phosphorus, and β2-microglobulin at various times. Total solute removal, dialyzer extraction ratios, and total cleared volumes were significantly larger during prolonged dialysis for urea, creatinine, phosphorus, and β2-microglobulin. Reduction ratios increased progressively, except for phosphate and β2-microglobulin, where the ratios remained constant after 2 h. In contrast, no significant difference was found for the reduction ratios of all solutes and Kt/Vurea between the three different sessions. With longer dialyses, solutes are efficiently removed from the deeper compartments of the patient's body. Our study shows that care must be taken when using Kt/Vurea or reduction ratios as the only parameters to quantify dialysis adequacy. Several studies have stressed the importance of dialysis time in the removal of uremic retention solutes. To further investigate this, nine stable chronic hemodialysis patients were dialyzed for 4, 6, or 8 h processing the same total blood and dialysate volume by the Genius system and high-flux FX80 dialyzers. Inlet blood and outlet dialysate were analyzed for urea, creatinine, phosphorus, and β2-microglobulin at various times. Total solute removal, dialyzer extraction ratios, and total cleared volumes were significantly larger during prolonged dialysis for urea, creatinine, phosphorus, and β2-microglobulin. Reduction ratios increased progressively, except for phosphate and β2-microglobulin, where the ratios remained constant after 2 h. In contrast, no significant difference was found for the reduction ratios of all solutes and Kt/Vurea between the three different sessions. With longer dialyses, solutes are efficiently removed from the deeper compartments of the patient's body. Our study shows that care must be taken when using Kt/Vurea or reduction ratios as the only parameters to quantify dialysis adequacy. One of the major aims of renal replacement therapy is to remove uremic waste products. The quantification of this removal is an important parameter in the assessment of adequacy of renal replacement therapy. Urea is currently used as the standard marker for dialysis adequacy, by the calculation of the clearance index Kt/Vurea or RR (reduction ratio).1.Sargent J.A. Shortfalls in the delivery of dialysis.Am J Kidney Dis. 1990; 15: 500-510Abstract Full Text PDF PubMed Scopus (83) Google ScholarKt/Vurea depends, however, on two separately modifiable factors: dialyzer clearance ‘K’ and dialysis time ‘t.’ As both factors might not have the same impact on solute removal, it is difficult to give a straightforward interpretation to the quantification of Kt/Vurea. Urea kinetics significantly differ from the kinetic behavior of other molecules, such as middle molecules, protein bound solutes, and even other small and water-solutes.2.Eloot S. Torremans A. De Smet R. et al.Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds.Kidney Int. 2005; 67: 1566-1575Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar,3.Gutzwiller J.P. Schneditz D. Huber A.R. et al.Estimating phosphate removal in haemodialysis: an additional tool to quantify dialysis dose.Nephrol Dial Transpl. 2002; 17: 1037-1044Crossref PubMed Scopus (65) Google Scholar Several studies stress the importance of time and/or clearance in the removal of difficult-to-remove uremic retention solutes. Dialyzer clearance K is a significant contributor to the removal of middle molecules such as β2-microglobulin, at least if pore size is sufficiently large.4.Clark W.R. Leypoldt J.K. Henderson L.W. et al.Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model.J Am Soc Nephrol. 1999; 10: 601-609PubMed Google Scholar,5.Goldfarb-Rumyantzev A.S. Cheung A.K. Leypoldt J.K. Computer simulation of small-solute and middle-molecule removal during short daily and long thrice-weekly hemodialysis.Am J Kidney Dis. 2002; 40: 1211-1218Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar The factor time plays an even more important role in the removal of middle molecules and phosphorus.3.Gutzwiller J.P. Schneditz D. Huber A.R. et al.Estimating phosphate removal in haemodialysis: an additional tool to quantify dialysis dose.Nephrol Dial Transpl. 2002; 17: 1037-1044Crossref PubMed Scopus (65) Google Scholar, 4.Clark W.R. Leypoldt J.K. Henderson L.W. et al.Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model.J Am Soc Nephrol. 1999; 10: 601-609PubMed Google Scholar, 5.Goldfarb-Rumyantzev A.S. Cheung A.K. Leypoldt J.K. Computer simulation of small-solute and middle-molecule removal during short daily and long thrice-weekly hemodialysis.Am J Kidney Dis. 2002; 40: 1211-1218Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 6.Raj D.S.C. Ouwendyk M. Francoeur R. et al.Beta(2)-microglobulin kinetics in nocturnal haemodialysis.Nephrol Dial Transpl. 2000; 15: 58-64Crossref PubMed Scopus (139) Google Scholar, 7.Fajardo L. Campistrus N. Rios P. et al.Evolution of serum phosphate in long intermittent hemodialysis.Kidney Int. 2003; 63: S66-S68Abstract Full Text Full Text PDF Scopus (15) Google Scholar, 8.Galland R. Traeger J. Arkouche W. et al.Short daily hemodialysis rapidly improves nutritional status in hemodialysis patients.Kidney Int. 2001; 60: 1555-1560Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 9.Mucsi I. Hercz G. Uldall R. et al.Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis.Kidney Int. 1998; 53: 1399-1404Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar, 10.Pohlmeier R. Vienken J. Phosphate removal and hemodialysis conditions.Kidney Int. 2001; 78: S190-S194Crossref Google Scholar, 11.Ratanarat R. Brendolan A. Volker G. et al.Phosphate kinetics during different dialysis modalities.Blood Purif. 2005; 23: 83-90Crossref PubMed Scopus (44) Google Scholar, 12.Vaithilingam I. Polkinghorne K.R. Atkins R.C. et al.Time and exercise improve phosphate removal in hemodialysis patients.Am J Kidney Dis. 2004; 43: 85-89Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar β2-Microglobulin removal is enhanced by increasing dialysis duration,4.Clark W.R. Leypoldt J.K. Henderson L.W. et al.Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model.J Am Soc Nephrol. 1999; 10: 601-609PubMed Google Scholar, 5.Goldfarb-Rumyantzev A.S. Cheung A.K. Leypoldt J.K. Computer simulation of small-solute and middle-molecule removal during short daily and long thrice-weekly hemodialysis.Am J Kidney Dis. 2002; 40: 1211-1218Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 6.Raj D.S.C. Ouwendyk M. Francoeur R. et al.Beta(2)-microglobulin kinetics in nocturnal haemodialysis.Nephrol Dial Transpl. 2000; 15: 58-64Crossref PubMed Scopus (139) Google Scholar whereas phosphorus removal has been linked to dialysis duration3.Gutzwiller J.P. Schneditz D. Huber A.R. et al.Estimating phosphate removal in haemodialysis: an additional tool to quantify dialysis dose.Nephrol Dial Transpl. 2002; 17: 1037-1044Crossref PubMed Scopus (65) Google Scholar, 7.Fajardo L. Campistrus N. Rios P. et al.Evolution of serum phosphate in long intermittent hemodialysis.Kidney Int. 2003; 63: S66-S68Abstract Full Text Full Text PDF Scopus (15) Google Scholar, 9.Mucsi I. Hercz G. Uldall R. et al.Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis.Kidney Int. 1998; 53: 1399-1404Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar, 11.Ratanarat R. Brendolan A. Volker G. et al.Phosphate kinetics during different dialysis modalities.Blood Purif. 2005; 23: 83-90Crossref PubMed Scopus (44) Google Scholar, 12.Vaithilingam I. Polkinghorne K.R. Atkins R.C. et al.Time and exercise improve phosphate removal in hemodialysis patients.Am J Kidney Dis. 2004; 43: 85-89Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar as well as to dialysis frequency.8.Galland R. Traeger J. Arkouche W. et al.Short daily hemodialysis rapidly improves nutritional status in hemodialysis patients.Kidney Int. 2001; 60: 1555-1560Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 9.Mucsi I. Hercz G. Uldall R. et al.Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis.Kidney Int. 1998; 53: 1399-1404Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar, 10.Pohlmeier R. Vienken J. Phosphate removal and hemodialysis conditions.Kidney Int. 2001; 78: S190-S194Crossref Google Scholar In all these studies, however, the factor time is not the only modified parameter with potential impact on adequacy. In general, in this type of studies, dialysate and blood flows are kept constant, so that it is impossible to assign changes in removal to time only, as prolonging or shortening will result in an increase or decrease of the global blood and dialysate volumes displaced. The Genius single-pass batch dialysis system (Fresenius Medical Care, Bad Homburg, Germany)13.Tersteegen B. Van Endert G. Patent DE198 31 15 665 A1.1982Google Scholar uses a double-sided roller pump that generates equal blood and dialysate flows up to 350 ml min−1 (Figure 1—point 1). In general, dialysis is ended when the entire volume of dialysate present in this system has crossed the dialyzer. As a consequence, dialysis sessions in spite of markedly different duration still will apply an identical blood and dialysate volume, hence offering the opportunity to evaluate the impact of time as the sole variable. The system consists of a closed dialysate tank of 90 l (Figure 1—point 4) and, although fresh and spent dialysate are stored together,13.Tersteegen B. Van Endert G. Patent DE198 31 15 665 A1.1982Google Scholar, 14.Fassbinder W. Renaissance of the batch method?.Nephrol Dial Transplant. 1998; 13: 3010-3012Crossref PubMed Scopus (16) Google Scholar, 15.Kleophas W. Haastert B. Backus G. et al.Long-term experience with an ultrapure individual dialysis fluid with a batch type machine.Nephrol Dial Transplant. 1998; 13: 3118-3125Crossref PubMed Scopus (60) Google Scholar dialysis may last up to 10 h when using a blood and dialysate flow of 150 ml min−1, without mixing of fresh and spent dialysate.16.Dhondt A. Eloot S. De Wachter D. et al.Dialysate partitioning in the Genius batch hemodialysis system: effect of temperature and solute concentration.Kidney Int. 2005; 67: 2470-2476Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar,17.Dhondt A.W. Vanholder R.C. De Smet R.V. et al.Studies on dialysate mixing in the Genius single-pass batch system for hemodialysis therapy.Kidney Int. 2003; 63: 1540-1547Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar The excess body water that is ultrafiltered out of the patient's plasma is collected in a filtrate recipient (Figure 1—point 3). In this study, we investigated the isolated effect of the factor time on the removal and kinetic behavior of different molecules such as urea, creatinine, phosphorus, and β2-microglobulin. The same patients were submitted to three different dialysis sessions with the Genius system lasting 4, 6, or 8 h, respectively, whereas blood flow rates were adapted so that the total processed volumes were matched at the end of all sessions. For the different time schedules, total solute removal (TSR) (panel a), total cleared volume (TCV) (b), dialyzer extraction ratio (c), and reduction ratio (d) are shown in Figure 2 for urea, creatinine, phosphorus, and β2-microglobulin. TSR was significantly larger with protracted dialysis for urea (P=0.006), creatinine (P=0.001), phosphorus (P<0.001), and β2-microglobulin (P=0.006) (Figure 2). Paired differences were found between the 4 and 8 h dialysis for all studied solutes (P=0.008 for urea, P<0.001 for creatinine, and P=0.004 for phosphorus and β2-microglobulin), whereas differences between the 4 and 6 h dialysis were found for creatinine (P=0.001) and phosphorus (P=0.008), and between the 6 and 8 h dialysis for urea (P=0.008) and phosphorus (P=0.027). Furthermore, TCV as well as dialyzer extraction ratio, which is a measure for global elimination in the dialyzer irrespective of flow, were significantly higher with a prolonged dialysis session for urea (both P=0.008), creatinine (both P<0.001), phosphorus (both P<0.001), and β2-microglobulin (P=0.029 and P=0.012) (Figure 2). No significant differences, however, were found between the different dialysis time schedules for the post-dialysis reduction ratio for all solutes under study. Furthermore, Kt/Vurea values were 1.39±0.28, 1.60±0.59, and 1.51±0.49 for the 4, 6, and 8 h dialysis (not significant). Figure 3 illustrates the reduction ratio at different time points during the 4, 6, and 8 h dialysis sessions for urea, creatinine, phosphorus, and β2-microglobulin. The reduction ratio is progressively increasing for urea, creatinine, and β2-microglobulin, and a difference in post-dialysis reduction ratio compared to the value at 120 min was found during the 4, 6, and 8 h dialysis, respectively, for urea (all P=0.008), CTN (creatinine) (all P=0.008), and during the 4 h dialysis for β2-microglobulin (P=0.031). For phosphorus (all sessions) and β2-microglobulin (6 and 8 h dialysis), however, RR remains constant from the 120th minute on for all sessions, and in individual patients, even an intradialytic rebound of phosphorus was observed. The percentage increase of TSR, TCV, dialyzer extraction ratio, and reduction ratio during a dialysis session of 6 and 8 h compared to 4 h dialysis is given in Table 1. Significant differences were found between the percentage increases during 8 h dialysis compared to the increases during 6 h dialysis for TSR of urea (P=0.012) and phosphorus (P=0.039), for TCV of urea (P=0.016), creatinine (P=0.008), and phosphorus (P=0.012), and for the dialyzer extraction ratio of urea (P=0.016), creatinine (P=0.008), and phosphorus (P=0.012). No differences were found for the reduction ratio, although it should be considered that standard deviations on the percentages were substantial, resulting in a low power at statistical testing.Table 1Percentage increase of TSR, TCV, dialyzer ER, and RR during a dialysis session of 6 and 8 h compared to 4 h dialysisTSRTCVERRR6 vs 4 h8 vs 4 h6 vs 4 h8 vs 4 h6 vs 4 h8 vs 4 h6 vs 4 h8 vs 4 hUrea6.126.1†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’0.733.3†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’1.033.2†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’4.11.1CTN21.735.516.732.1†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’17.132.0†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’-2.9-0.3P26.748.9†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’22.432.5†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’22.732.4†P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’2.1-5.8β2M42.581.248.594.448.994.35.29.3β2M, β2-microglobulin; CTN, creatinine; ER, extraction ratio; RR, reduction ratio; P, phosphorus; TSR, total solute removal; TCV, total cleared volume.† P<0.05 percentages ‘8 vs 4 h’ vs ‘6 vs 4 h.’ Open table in a new tab β2M, β2-microglobulin; CTN, creatinine; ER, extraction ratio; RR, reduction ratio; P, phosphorus; TSR, total solute removal; TCV, total cleared volume. Finally, as the urea dialyzer clearances at the end of dialysis were not significantly different from those at 5 min, and variations were even inconsistent, efficient Genius operation without recirculation of spent dialysate was obtained for all applied dialysis time schedules over the entire observation period. Although most studies evaluate the impact of dialysis time on solute removal by varying more than one parameter affecting dialysis adequacy, we investigated the isolated effect of time on the removal of urea, creatinine, phosphorus, and β2-microglobulin, and this using different modalities to express dialysis adequacy. Patients were undergoing three different dialysis sessions with the Genius system, lasting for 4, 6, and 8 h, respectively, whereas total volume of processed blood and dialysate remained the same. The most striking result of this study is that protracting dialysis time results in a higher total amount of solute removed from the patient's body, whereas Kt/Vurea is not able to detect this difference. Although previous studies illustrated the positive impact of longer dialysis only for the removal of solutes such as β2-microglobulin4.Clark W.R. Leypoldt J.K. Henderson L.W. et al.Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model.J Am Soc Nephrol. 1999; 10: 601-609PubMed Google Scholar, 5.Goldfarb-Rumyantzev A.S. Cheung A.K. Leypoldt J.K. Computer simulation of small-solute and middle-molecule removal during short daily and long thrice-weekly hemodialysis.Am J Kidney Dis. 2002; 40: 1211-1218Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 6.Raj D.S.C. Ouwendyk M. Francoeur R. et al.Beta(2)-microglobulin kinetics in nocturnal haemodialysis.Nephrol Dial Transpl. 2000; 15: 58-64Crossref PubMed Scopus (139) Google Scholar and phosphorus,3.Gutzwiller J.P. Schneditz D. Huber A.R. et al.Estimating phosphate removal in haemodialysis: an additional tool to quantify dialysis dose.Nephrol Dial Transpl. 2002; 17: 1037-1044Crossref PubMed Scopus (65) Google Scholar, 7.Fajardo L. Campistrus N. Rios P. et al.Evolution of serum phosphate in long intermittent hemodialysis.Kidney Int. 2003; 63: S66-S68Abstract Full Text Full Text PDF Scopus (15) Google Scholar, 9.Mucsi I. Hercz G. Uldall R. et al.Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis.Kidney Int. 1998; 53: 1399-1404Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar, 11.Ratanarat R. Brendolan A. Volker G. et al.Phosphate kinetics during different dialysis modalities.Blood Purif. 2005; 23: 83-90Crossref PubMed Scopus (44) Google Scholar, 12.Vaithilingam I. Polkinghorne K.R. Atkins R.C. et al.Time and exercise improve phosphate removal in hemodialysis patients.Am J Kidney Dis. 2004; 43: 85-89Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar we found that prolonged dialysis is also effective for small and water-soluble solutes such as urea and creatinine. This result is remarkable, as we were dealing with an equal amount of processed blood in all sessions. The significant larger TSR and TCV for longer dialysis, however, conform with the fact that the dialyzer extraction ratio, which is a relative clearance, also was higher. This can be attributed to a higher driving force for mass transfer in the dialyzer, as dialyzer inlet concentrations remain higher for slower and longer dialysis due to more pronounced concentration shifts during dialysis from the tissue toward the blood and plasma compartment. Furthermore, as a decreased dialysate flow, as the only changed parameter, results in a smaller extraction ratio,18.Allen R. Frost T.H. Hoenich N.A. The influence of the dialysate flow rate on hollow fiber hemodialyzer performance.Artif Organs. 1995; 19: 1176-1180Crossref PubMed Scopus (20) Google Scholar,19.Leypoldt J.K. Cheung A.K. Agodoa L.Y. et al.Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The Hemodialysis (HEMO) Study.Kidney Int. 1997; 51: 2013-2017Abstract Full Text PDF PubMed Scopus (107) Google Scholar whereas a decreased blood flow is known to barely improve extraction from the dialyzer in case of pure diffusive transport, our study clearly indicates that the time factor plays the major role compared to the changes in applied flow rates. However, it should be remarked that total solute removed during two successive 4 h dialysis sessions at high flow rates might be higher than that during a single prolonged dialysis session of 8 h at decreased flow rates. Although urea reduction ratio and Kt/Vurea are often used to estimate dialysis adequacy, this study did not find any differences in these values, in spite of the significantly larger TSR during prolonged dialysis. As slowing down dialysis flows allows more shifts of solute out of the extraplasmatic compartments, compartmental behavior of the different solutes will be different when dialysis duration is extended, allowing a higher absolute amount of solute removal in spite of no differences in RR and Kt/Vurea. Quantifying the adequacy of different dialysis strategies only with the use of Kt/Vurea or urea reduction ratios will thus lead to erroneous conclusions, if the time frame of the tested modalities is different. This finding is not surprising for phosphorus, as the removal of phosphorus has previously been described by a four-compartmental kinetic model,20.Spalding E.M. Chamney P.W. Farrington K. Phosphate kinetics during hemodialysis: evidence for biphasic regulation.Kidney Int. 2002; 61: 655-667Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar where the third and fourth compartment release phosphorus in the extracellular and intracellular compartment, respectively, after the intracellular concentration drops below a threshold concentration. This phenomenon is reflected by the stabilization of phosphorus concentration during the course of dialysis (Figure 3). However, the impact of long and slow dialysis on solutes such as urea, creatinine, and β2-microglobulin, which are rather following a two-pool model,4.Clark W.R. Leypoldt J.K. Henderson L.W. et al.Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model.J Am Soc Nephrol. 1999; 10: 601-609PubMed Google Scholar, 21.Gotch F. Levin N. Zasuwa G. et al.Kinetics of beta-2-microglobulin in hemodialysis.Contrib Nephrol. 1989; 74: 132-138Crossref PubMed Google Scholar, 22.Maasrani M. Jaffrin M.Y. Fischbach M. et al.Urea, creatinine and phosphate kinetic modeling during dialysis: application to pediatric hemodialysis.Int J Artif Organs. 1995; 18: 122-129PubMed Google Scholar, 23.Schneditz D. Daugirdas J.T. Compartment effects in hemodialysis.Semin Dial. 2001; 14: 271-277Crossref PubMed Scopus (0) Google Scholar, 24.Leypoldt J.K. Cheung A.K. Deeter R.B. Rebound kinetics of beta2-microglobulin after hemodialysis.Kidney Int. 1999; 56: 1571-1577Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 25.Stiller S. Xu X.Q. Gruner N. et al.Validation of a two-pool model for the kinetics of beta2-microglobulin.Int J Artif Organs. 2002; 25: 411-420Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar was also significant. This finding conforms to the results of a theoretical study based on kinetic modeling of different small and water-soluble compounds.2.Eloot S. Torremans A. De Smet R. et al.Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds.Kidney Int. 2005; 67: 1566-1575Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar,26.Eloot S. De Smet R. Verdonck P. et al.Should we dialyze more frequently or prolonged to remove uremic toxins, other than urea?.Int J Artif Organs. 2005; 29: 883Google Scholar It was revealed that solutes that are distributed in a small total volume and behave like one-compartmental solutes take most advantage of short daily dialysis sessions, whereas solutes characterized by a large total distribution volume divided into at least two compartments take more advantage of a prolonged dialysis treatment, three times a week. The major clinical impact of such a prolonged dialysis is the attenuated post-dialysis rebound phenomenon and the lower mean solute concentration in the patient. Thus, overall uremic toxicity is lower resulting in less adverse uremic effects and improved patient well-being. Furthermore, accounting for the present results as well as for the native kidney function, it is obvious that the lowest mean patient concentrations are registered for a daily prolonged dialysis. Hence, our data underscore the importance of improving dialytic removal by modifying relevant parameters inducing beneficial kinetic shifts and enhancing removal out of second or even more distal compartments. Finally, it should be remarked that the presented data is based on the results of a single dialysis session of each investigated time schedule with a limited number of patients. Nevertheless, our study clearly indicates that a prolonged dialysis session is favorable compared to standard 4 h dialysis, due to the larger amount of solute removal and a decreased solute content in the patient in the interdialytic period. Although several studies have already reported about the importance of time in the removal of difficult-to-remove uremic retention solutes, the factor time was not the only parameter with a potential impact on adequacy that was modified in those studies. Therefore, we investigated the isolated effect of the time factor on the removal and kinetic behavior of different molecules such as urea, creatinine, phosphorus, and β2-microglobulin. For the different sessions lasting 4, 6, and 8 h, reduction ratios were not significantly different, whereas TSRs, dialyzer extraction ratios, and TCVs were higher for prolonged dialysis.
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