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Water permeability of high-flux dialyzer membranes after Renalin reprocessing

2007; Elsevier BV; Volume: 71; Issue: 11 Linguagem: Inglês

10.1038/sj.ki.5002212

1523-1755

Mohamed E. Labib, J. Murawski, Y. Tabani, Susanne Wolff, Andrew L. Zydney, F. R. Funderburk, Zhiwei Huang, Toros Kapoian, Richard A. Sherman,

Erythropoietin and Anemia Treatment

Dialysis with high-flux membranes is widely used, in part, because they are thought to increase the removal of middle molecules when compared with low-flux membranes. Dialyzer reprocessing; however, is thought to alter middle molecule clearance. Renalin, a mixture of germicidal agents, has widespread use in dialyzer reprocessing. We determined the effect of Renalin reprocessing on the water permeability of three different dialyzers of Fresenius (F80A and 200A) and Gambro (17R) manufacture using the dead-end filtration method. Two hundred and seventeen, predominantly used but some new, dialyzers were evaluated. Water permeability of the used, but not the new, dialyzers fell abruptly and dramatically with reprocessing. The permeability fell almost 70% in the F80A dialyzer after three reprocessing procedures with similar, but somewhat slower declines, seen in the other two dialyzers. We conclude that there is a decline in water permeability seen in Renalin reprocessed dialyzers. This factor and the associated change in solute clearance and ultrafiltration characteristics should be considered in assessing the effectiveness of dialyzer reprocessing. Dialysis with high-flux membranes is widely used, in part, because they are thought to increase the removal of middle molecules when compared with low-flux membranes. Dialyzer reprocessing; however, is thought to alter middle molecule clearance. Renalin, a mixture of germicidal agents, has widespread use in dialyzer reprocessing. We determined the effect of Renalin reprocessing on the water permeability of three different dialyzers of Fresenius (F80A and 200A) and Gambro (17R) manufacture using the dead-end filtration method. Two hundred and seventeen, predominantly used but some new, dialyzers were evaluated. Water permeability of the used, but not the new, dialyzers fell abruptly and dramatically with reprocessing. The permeability fell almost 70% in the F80A dialyzer after three reprocessing procedures with similar, but somewhat slower declines, seen in the other two dialyzers. We conclude that there is a decline in water permeability seen in Renalin reprocessed dialyzers. This factor and the associated change in solute clearance and ultrafiltration characteristics should be considered in assessing the effectiveness of dialyzer reprocessing. High-flux dialysis has come into widespread use. One reason for this is the remarkably better removal of so called 'middle molecules' with high flux compared with low-flux membranes. However, dialyzer reprocessing may alter middle molecule clearance, the subject of a growing number of investigations in recent years. These alterations, typically assessed by examining beta-2-microglobulin clearance, vary greatly depending on the specific cleaning and sterilization procedures utilized as well as the membrane being reprocessed.1.Cheung A.K. Agoda L.Y. Daugirdas J.T. et al.Effects of hemodialyzer reuse on clearances of urea and beta-2 microglobulin.J Am Soc Nephrol. 1999; 10: 117-127PubMed Google Scholar,2.Clark W. Mueller B. Scott M. et al.Low-molecular weight protein removal by high-flux dialyzers: basic mechanisms and effect of reprocessing.Semin Dial. 1999; 12: 254-349Google Scholar Beta-2-microglobulin clearance may be linked to mortality in dialysis patients,3.Cheung A.K. Rocco M.V. Yan G. et al.Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study.J Am Soc Nephrol. 2006; 17: 546-555Crossref PubMed Scopus (335) Google Scholar as suggested by a new analysis of the Hemodialysis (HEMO) study. Renalin, a proprietary mixture of peroxyacetic acid, acetic acid, and hydrogen peroxide, is the most widely utilized germicide for reprocessing dialyzers. It is most often used as an agent without bleach because of the potential generation of toxic vapors if the bleach is not fully rinsed before Renalin reprocessing. The effect of repeated Renalin reprocessing on the dialyzer's properties varies somewhat with the membrane. Most clinical studies have shown that Renalin produces little change in urea clearance as long as the fiber bundle volume is at least 80% of the initial fiber bundle volume. There is, however, extensive evidence that Renalin reprocessing is associated with a loss in beta-2-microglobulin clearance.1.Cheung A.K. Agoda L.Y. Daugirdas J.T. et al.Effects of hemodialyzer reuse on clearances of urea and beta-2 microglobulin.J Am Soc Nephrol. 1999; 10: 117-127PubMed Google Scholar, 2.Clark W. Mueller B. Scott M. et al.Low-molecular weight protein removal by high-flux dialyzers: basic mechanisms and effect of reprocessing.Semin Dial. 1999; 12: 254-349Google Scholar, 4.Rockel A. Hertel J. Fiegel P. et al.Permeability and secondary membrane formation of a high flux polysulfone hemofilter.Kidney Int. 1986; 30: 429-432Abstract Full Text PDF PubMed Scopus (104) Google Scholar, 5.Ouseph R. Smith B.P. Ward R.A. Maintaining blood compartment volumes in dialyzers reprocessed with peracetic acid maintains Kt/V but not beta-2 microglobulin removal.Am J Kidney Dis. 1997; 30: 501-506Abstract Full Text PDF PubMed Scopus (24) Google Scholar, 6.Leypoldt J.K. Cheung A.K. Deeter R.B. Effect of hemodialyzer reuse: dissociation between clearances of small and large solutes.Am J Kidney Dis. 1998; 32: 295-301Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar For example, the HEMO study found a 67.2% reduction in beta-2-microglobulin clearance for CT190 dialyzers after 10–14 reprocessing cycles.1.Cheung A.K. Agoda L.Y. Daugirdas J.T. et al.Effects of hemodialyzer reuse on clearances of urea and beta-2 microglobulin.J Am Soc Nephrol. 1999; 10: 117-127PubMed Google Scholar In the HEMO study, as well as in other clinical studies, beta-2-microglobulin clearance was assessed by changes in patient serum levels taking into account the effect of ultrafiltration-induced hemoconcentration. Clearance estimates thus included beta-2-microglobulin removal by mass transfer as well as adsorption to the membrane. Adsorptive losses of beta-2-microglobulin can be quite significant depending on the surface properties of the membrane. For example, Ward and Ouseph7.Ward R.A. Ouseph R. Impact of bleach cleaning on the performance of dialyzers with polysulfone membranes processed for reuse using peracetic acid.Artif Organs. 2003; 27: 1029-1034Crossref PubMed Scopus (13) Google Scholar estimated that as much as 60% of the beta-2-microglobulin clearance through Fresenius F80B polysulfone dialyzers was due to adsorption. Thus, it is difficult to extrapolate data for beta-2-microglobulin to the clearance of other important molecules. Several in vitro studies have been performed to obtain more quantitative insights into the effects of Renalin reprocessing on dialyzer membranes. For example, Wolff and Zydney8.Wolff S.H. Zydney A.L. Effects of peracetic acid reprocessing on the transport characteristics of polysulfone hemodialyzers.Artif Organs. 2005; 29: 166-173Crossref PubMed Scopus (8) Google Scholar found a significant reduction in dextran clearance for Fresenius F80A dialyzers after cleaning with peracetic acid following a 3-h in vitro dialysis session using human plasma. There was also a corresponding reduction in the membrane hydraulic permeability or ultrafiltration coefficient. However, it is difficult to determine the clinical significance of these results, as the hemodialysis was performed with donated anticoagulated plasma with no exposure to any of the formed elements in blood. The objective of this work was to obtain quantitative data for the effect of Renalin reprocessing on dialyzer water permeability, using the dead-end filtration method and clearance characteristics, using polydisperse dextrans as model solutes. Data were obtained using several different dialyzer types, with the permeability and clearance evaluated for clinically used dialyzers after multiple reprocessing cycles using Renalin as the cleaning and storage agent. Water permeability fell dramatically with reprocessing with all three dialyzers. The zero reuse condition is distinct from the remainder of the in vivo reuse data (Figure 1). The most dramatic decline in permeability occurred after the first reuse. Data for the 200A dialyzers showed an average 46% reduction in permeability after a single reuse, whereas the 17R dialyzers showed a 39% reduction. The permeability for both the 200A and the 17R showed a small but gradual persistent decline with increasing reuse number. In contrast, data for the F80A showed a 67% decline in permeability after three reuses; no data were obtained for this particular dialyzer after only a single reuse. In contrast to the results with the 200A and 17R dialyzers, the permeability for the F80A remained essentially constant from three to 25 reuse cycles. Regression analyses were undertaken to more precisely model the observed effects. In the first model, the permeability values for the zero reuse condition were included along with the permeability values associated with the other reuse values as the dependent variable. Independent variables in the regression were type of dialyzer and reuse condition (including the zero reuse condition). The potential interaction between these predictor variables as well as linear, quadratic, and cubic components of the change in permeability over successive reuses was included in the model. The results indicated significant effects for the linear, quadratic, and cubic effect of reuse (P<0.01), an interaction between type of dialyzer and days of reuse (P<0.05) as well as a main effect for type of dialyzer (P<0.001). Overall, the Gambro 17R dialyzers showed greater permeability than the other dialyzers. This model, illustrated in Figure 1, accounted for 83% of the variance in the observed permeability values. The second regression model was concerned with predicting only the permeability values for the reprocessed dialyzers. The zero reuse condition and associated permeability scores were therefore not included in the analysis. Independent and dependent variables were the same as those included in the first model considered. The results indicated a main effect for type of dialyzer (P<0.001), linear and quadratic effects for number of reuses (P<0.05), and an interaction between dialyzer type and number of reuses (P<0.05). Overall, the Fresenius 80A dialyzer was significantly less permeable, and the Gambro 17R was significantly more permeable than the Fresenius 200A. Compared with the other dialyzers, the Gambro 17R showed a greater absolute rate of decrease in permeability (although a similar fractional rate of decline as the Fresenius 200A) over the range of reuses studied. This model accounted for 81% of the variance in permeability values during this phase of the study. In order to obtain additional insights into the effects of Renalin reprocessing on dialyzer transport, a limited set of experiments were performed to evaluate the dextran clearance for new and clinically used Gambro 17R dialyzers (Table 1). The clearance of all dextrans decreased significantly after only a single-reuse cycle, with the reduction in clearance being greatest for the largest molecular weight dextran. The dextran clearance continued to decrease after additional reprocessing cycles using Renalin. The clearance of the 10 kDa dextran decreased by 80% after seven cycles, whereas the clearance of the 25 kDa dextran was below detectable limits (less than l ml/min). These results are consistent with in vitro measurements obtained by Wolff and Zydney8.Wolff S.H. Zydney A.L. Effects of peracetic acid reprocessing on the transport characteristics of polysulfone hemodialyzers.Artif Organs. 2005; 29: 166-173Crossref PubMed Scopus (8) Google Scholar for Fresenius F80A dialyzers reprocessed with peracetic acid.Table 1Effect of Renalin reprocessing on Lp and convective clearance of dextran probe of Polyflux dialyzersaDialyzers were used in dialysis treatment.Percentage decrease of new dialyzer – Gambro 17RNumber of uses0 (new)137LP (% of new)100606055Dextran clearance (% of new) (kDa)51007565531010057382015100402072010021105251001050a Dialyzers were used in dialysis treatment. Open table in a new tab Automated Renalin reprocessing without bleach substantially reduced the water permeability in the three high-flux dialyzer types included in this study. This decline was seen after only a single reuse, indicating that Renalin reprocessing modifies the permeability barrier of these dialyzers for all subsequent dialysis sessions. The reused Optiflux 200A and Gambro 17R dialyzers showed a small continued decline in permeability after multiple reprocessing cycles, suggesting that there are two phases involved in the reduction in water permeability for these membranes. Although the reduction in water permeability would not have any adverse effect on the ability of the dialyzers to achieve the necessary fluid removal during dialysis, the results suggest that the loss in water permeability may be directly related to the reduction in middle molecule (specifically, beta-2-microglobulin) clearance noted with Renalin reprocessing by other investigators.2.Clark W. Mueller B. Scott M. et al.Low-molecular weight protein removal by high-flux dialyzers: basic mechanisms and effect of reprocessing.Semin Dial. 1999; 12: 254-349Google Scholar There are two possible explanations for this relationship. First, the reduction in water permeability and solute clearance may both be due to the presence of residual protein on and within the membrane pores, with this protein deposit providing an additional resistance to both water and solute transport through the dialysis membrane.9.Morti S.M. Zydney A.L. Protein–membrane interactions during hemodialysis: effects on solute transport.ASAIO J. 1998; 44: 319-326Crossref PubMed Google Scholar The data obtained in this study for clinically reprocessed dialyzers indicate that Renalin is unable to remove the deposited protein from on the surface and within the membrane pores. In addition to the change in water permeability, there was also a dramatic reduction in the dextran clearance, particularly for the larger molecular weight dextrans. This behavior is consistent with the observed reduction in beta-2-microglobulin clearance seen in many clinical studies, although in this case the change in dextran clearance is entirely due to changes in mass transfer, as dextran adsorption to the membranes was negligible in these experiments (data not shown). The dextran data also clearly demonstrate the importance of the solute molecular weight in determining the magnitude of the reduction in clearance. For example, the clearance of a 5 kDa dextran through the Gambro 17R dialyzer decreased by 25% after a single-reuse cycle, whereas the clearance of the 25 kDa dextran through the same dialyzer decreased by 90%. This reduction in dextran clearance is likely due to the presence of residual protein on and within the membrane pores even after reprocessing with Renalin (vide supra). In conclusion, in the clinical setting, Renalin processing causes a significant reduction in water permeability in high-flux dialyzers, at least with the three dialyzers examined in this study. Changes in dialyzer water permeability, solute clearance, and ultrafiltration characteristics should be considered when evaluating the effectiveness of dialyzer reprocessing. Data were obtained using Fresenius F80A, Fresenius Optiflux 200A (Fresenius Medical Care, Bad Homburg, Germany), and Gambro 17R dialyzers (Gambro Renal Products, Lakewood, CO, USA). The description of these dialyzer compositions and their fiber microstructure is given elsewhere.10.Mishkin G.J. What clinically important advances in understanding and improving dialyzer function have occurred recently?.Semin Dial. 2001; 14: 170-173Crossref Google Scholar,11.Cornelius R.M. McClung W.G. Richardson R.M. et al.Effects of heat/citric acid reprocessing on high-flux polysulfone dialyzers.ASAIO J. 2002; 48: 45-56Crossref PubMed Scopus (8) Google Scholar Dialyzers were utilized clinically and were arbitrarily removed from service after a varying number of reuses for in vitro assessment of water permeability and dextran clearance. In addition, new dialyzers were studied after thorough rinsing with phosphate buffer. Routine dialyzer reprocessing utilized the Renatron II (Renal Systems, Division of Minntech Corp., Minneapolis, MN, USA) and followed the procedure outlined by the manufacturer, for both new and clinically used dialyzers. One hundred and eighty-six used patient dialyzers (39, F80A; 78, 200A; and 69, 17R) and 31 new dialyzers (4, F80A; 11, 200A; and 16, 17R) were evaluated using the dead-end filtration method.9.Morti S.M. Zydney A.L. Protein–membrane interactions during hemodialysis: effects on solute transport.ASAIO J. 1998; 44: 319-326Crossref PubMed Google Scholar In the dead-end filtration method (Figure 2), the permeability measurements involve applying a positive pressure of 517 mm Hg on one of the dialysate-side ports (a), with the other dialysate-side port (b) and one of the blood ports (c) closed; the volumetric flow rate Q (ml/min) is then measured through the remaining blood-side port (d). Applying the positive pressure from the dialysate-side (a) and collecting the permeated water from the blood-side (d), or applying the positive pressure from the blood-side (d) and collecting the permeated water from the dialysate-side (a) gives the same filtration rate. Deionized water was used to perform all permeability testing. The permeability Lp (ml/h/mm Hg) was evaluated as:Lp=Q*60517 The dextran clearance was determined by the following method. Fluid was pumped counter currently through both the blood and dialysate sides of the dialyzer using previously calibrated MasterFlex peristaltic pumps. The dialysate solution was used in a single-pass mode at a flow rate of 500 ml/min. The blood-side fluid was identical to the dialysate but with added dextrans. The polydisperse dextrans allow data to be obtained over a broad range of solute molecular weights in a single experiment. The use of dextrans for characterization of dialysis membranes is well established.9.Morti S.M. Zydney A.L. Protein–membrane interactions during hemodialysis: effects on solute transport.ASAIO J. 1998; 44: 319-326Crossref PubMed Google Scholar,12.Kunas G.A. Burke R.A. Brierton M.A. Ofsthun N.J. The effect of blood contact and reuse on the transport properties of high-flux dialysis membranes.ASAIO J. 1996; 42: 288-294Crossref PubMed Scopus (16) Google Scholar The 'blood' flow rate was maintained at 300 ml/min. Data were obtained at zero net ultrafiltration, achieved by manually adjusting the valve on the lumen outflow to maintain a constant fluid level in the solution reservoir. The temperature was set at 37°C using a temperature controller on the blood-side solution and an immersion heater on the dialysate-side. The system was allowed to stabilize by passing about 1 l of solution through both the blood and dialysate-side inlets in a single-pass mode. After stabilization, the inlet and exit tubing on the blood-side were placed in a solution reservoir, and samples were collected from the reservoir over time. Concentrations of the different molecular weight dextrans were determined by size exclusion chromatography using an Agilent 1100 Chromatography system with a TSK2000 column (Tosoh Corporation, Tokyo, Japan). Phosphate-buffered saline was used as the eluent, with the dextran concentrations evaluated by refractive index detection. Dextran clearance was evaluated directly from the change in dextran concentration in the reservoir as a function of time as described by Morti and Zydney.9.Morti S.M. Zydney A.L. Protein–membrane interactions during hemodialysis: effects on solute transport.ASAIO J. 1998; 44: 319-326Crossref PubMed Google Scholar Data analysis focused on characterizing the relationship between in vivo reuse of the patient dialyzers and the permeability of the dialyzers as measured by the dead-end filtration method. This was undertaken using a set of hierarchical regression/correlation procedures.13.Cohen J. Cohen P. West S.G. Aiken L.S. Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences. 3rd edn. Lawrence Earlbaum, Mahwah, NJ2003Google Scholar Two analyses were undertaken. The first examined the regression model with the zero reuse points included in the analysis. The second excluded those points. This approach provides a way for us to examine the relationship between key variables from two distinct points of view. In each of the analyses, the type of dialyzer was entered as a categorical (dummy-coded) variable, whereas reuse was entered as a real number variable. The interaction of dialyzer type and reuse was carried by product variables as a function of their order of entry into the regression equation.