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• W2072138214 abstract "The quality of dialysate: An integrated approach. The role of bacterial contamination of dialysis water with respect to chronic inflammatory diseases associated with long-term hemodialysis therapy has been greatly underestimated in the last two decades. In the present article, recent multicenter studies assessing the bacteriological quality of water and dialysate are discussed. In addition, we describe that pyrogenic substances of bacterial origin derived from contaminated dialysate penetrate intact dialyzer membranes with the consequence of the induction of an inflammatory response in the patients. The influence of dialyzer membrane characteristics on the passage of bacterial substances from dialysate into blood are discussed. Reaching the patients blood, bacteria-derived substances activate circulating mononuclear cells to produce proinflammatory cytokines. Cytokines such as interleukin-1β and tumor necrosis factor-α are mediators of the acute phase response resulting in elevated levels of acute phase proteins (for example, C-reactive protein). The consequence is a state of microinflammation that may contribute to progressive inflammatory diseases in chronic renal failure such as β2-microglobulin amyloidosis, protein catabolism, and atherosclerosis. The use of sterile dialysate reduces cytokine production and plasma levels of acute phase proteins, and may positively influence progressive inflammatory diseases in patients with end-stage renal failure. The quality of dialysate: An integrated approach. The role of bacterial contamination of dialysis water with respect to chronic inflammatory diseases associated with long-term hemodialysis therapy has been greatly underestimated in the last two decades. In the present article, recent multicenter studies assessing the bacteriological quality of water and dialysate are discussed. In addition, we describe that pyrogenic substances of bacterial origin derived from contaminated dialysate penetrate intact dialyzer membranes with the consequence of the induction of an inflammatory response in the patients. The influence of dialyzer membrane characteristics on the passage of bacterial substances from dialysate into blood are discussed. Reaching the patients blood, bacteria-derived substances activate circulating mononuclear cells to produce proinflammatory cytokines. Cytokines such as interleukin-1β and tumor necrosis factor-α are mediators of the acute phase response resulting in elevated levels of acute phase proteins (for example, C-reactive protein). The consequence is a state of microinflammation that may contribute to progressive inflammatory diseases in chronic renal failure such as β2-microglobulin amyloidosis, protein catabolism, and atherosclerosis. The use of sterile dialysate reduces cytokine production and plasma levels of acute phase proteins, and may positively influence progressive inflammatory diseases in patients with end-stage renal failure. Why is the bacterial contamination of water and dialysate an issue today? The bacteriological quality of dialysate has been improved substantially during the last 20 years because of the worldwide use of reverse osmosis units in the water-preparation systems. On the other hand, the almost universal use of sodium bicarbonate instead of sodium acetate to buffer dialysate has increased the risk of severe bacterial contamination of dialysate. This is due to the fact that bicarbonate promotes the growth of microorganisms commonly detected in water and dialysate. So called water-born bacteria include several Pseudomonas species, including P. aeruginosa, P. maltophilia, and P. vesicularis, as well as other gram-negative bacteria such as Alcaligenes species, Moraxella, and Corynebacteria. In addition, several species of fungi and yeast can be found[1Pass T. Wright R. Sharp B. Harding G.B. Culture of dialysis fluids on nutrient-rich media for short periods at elevated temperatures underestimate microbial contamination.Blood Purif. 1996; 14: 136-145Crossref PubMed Scopus (51) Google Scholar]. Lipopolysaccharides (LPSs) and peptidoglycans are the main structural components of the outer cell wall of gram-negative microorganisms. These large substances of bacterial origin and their fragments of small molecular sizes are released from bacterial debris. Together with matrix proteins and exotoxins, which are actively secreted from living bacteria, LPS and peptidoglycans form a second layer called biofilm on the inner surface of water and dialysate tubings. From this biofilm, bacterial fragments of various molecular sizes may be released into the flowing dialysate in an unpredictable manner and may reach the dialyzer in which these substances of bacterial origin are separated from the patient's blood only by the semipermeable dialyzer membrane. If LPSs (endotoxins), peptidoglycans, exotoxins, and their fragments of small molecular weight (<5 kD) penetrate intact dialyzer membranes, they will induce an inflammatory response in the patients and eventually a febrile reaction. Because of the risk of pyrogenic reactions, the pyrogen permeability of dialyzer membranes is an important aspect with respect to dialyzer biocompatibility. This issue became of particular importance, since high-flux membranes with high ultrafiltration coefficients and the occurrence of backfiltration are increasingly used. More recently, multipurpose dialysis monitors producing dialysate as well as replacement fluid for online hemofiltration and hemodiafiltration have been introduced. Since in the latter treatment modalities the online produced dialysate is infused directly into the blood stream of the patient, it has to be sterile and pyrogen free. The obvious clinical effect of hemodialysis with severely contaminated dialysate is a pyrogenic reaction with fever and cardiovascular instability. According to data from the United States, approximately 22% of hemodialysis centers report more than one pyrogenic reaction per year[2Tokars J.I. Alter M.J. Miller E. Moyer L.A. Favero M.S. National surveillance of dialysis associated diseases in the United States-1994.ASAIO J. 1997; 43: 108-119PubMed Google Scholar]. This number remained stable in the years from 1989 until 1994, despite improvements in the water pretreatment systems. According to these data, one can estimate the incidence of pyrogenic reactions to be approximately 1:10,000 hemodialysis treatment sessions. With respect to progressive inflammatory diseases (amyloidosis, catabolism) or progressive diseases with a contributing role of low-grade inflammation (atherosclerosis), subclinical effects such as the activation of monocytes, macrophages, and neutrophils with the subsequent production and release of proinflammatory cytokines and acute phase proteins seem to be highly relevant. The following paragraphs discuss the degree of bacterial contamination in dialysate in modern dialysis units and important aspects concerning the monitoring of the bacteriological quality of dialysate. In vitro dialysis experiments describing factors influencing the permeability of different dialyzer membranes are discussed. Furthermore, a series of in vivo studies is discussed, in which the use of sterile dialysate reduces monocyte activation, cytokine production, and plasma levels of acute phase proteins. Finally, we deal with investigations (both basic and clinical) suggesting that a reduction or even prevention of a subclinical inflammatory response may reduce the prevalence, decrease the severity, or slow down the progression of life-threatening complications of long-term hemodialysis such as β2-microglobulin amyloidosis, muscle protein wasting, and atherosclerosis. In the beginning of routine hemodialysis therapy when only softeners were used to prepare dialysis water and dialysate was mixed and heated to 37°C in tanks, severe bacterial contamination of dialysate was very common and resulted in pyrogenic reactions most likely caused by the passage of bacterial endotoxin from dialysate into blood via membrane ruptures in the self-made Kiil dialyzers. Standards concerning the bacteriological quality of dialysis water have been proposed. The guidelines of the American Association of Medical Instrumentation (AAMI) allow bacterial growth of no more than 200 colony-forming units (CFU)/mL in water and 2000 CFU/mL in dialysate. In addition to bacterial growth, there are also standards concerning the endotoxin concentration in water and dialysate. The AAMI standards allow up to 5 endotoxin units (EU) per milliliter in water as well as in dialysate. More recently, the German Renal Society, Deutsche Arbeitsgemeinschaft für klinische Nephrologie (DafKN), proposed better standards, allowing only 100 CFU/mL of bacterial growth and 0.25 EU/mL of endotoxin in water. These standards were adopted from the European Pharmacopoe for drinking water. With respect to dialysate contamination, the DAfKN recommends upper limits of 1000 CFU/mL and 0.5 EU/mL for bacterial growth and endotoxin, respectively. The definition of sterile fluid is a content of less than 10-6 CFU/mL (<1 CFU in 1000 L) and no detectable endotoxin (detection limit of the endotoxin assays 0.03 EU/mL). This definition cannot be used to describe the quality of dialysate produced by online hemodialysis monitors, because 1000 L are never produced in one session. To overcome this problem, the new term “ultrapure” has been created. Today, there is no standard for ultrapure fluid, but there is a general agreement that ultrapure dialysate should contain less than 0.1 CFU/mL and no detectable endotoxin (<0.03 EU/mL). Bacterial growth in water and dialysate samples is dramatically influenced by the microbiological methods applied[1Pass T. Wright R. Sharp B. Harding G.B. Culture of dialysis fluids on nutrient-rich media for short periods at elevated temperatures underestimate microbial contamination.Blood Purif. 1996; 14: 136-145Crossref PubMed Scopus (51) Google Scholar]. These mentioned standards are only valid in combination with the use of appropriate techniques. To determine bacterial growth in water and dialysate correctly, it is highly recommended to use nutrient-poor agar [R2A, or tryptone glucose extract (TGE)] in plate count agar methods, and a prolonged incubation time of seven days at room temperature (17 to 23°C) instead of body temperature[1Pass T. Wright R. Sharp B. Harding G.B. Culture of dialysis fluids on nutrient-rich media for short periods at elevated temperatures underestimate microbial contamination.Blood Purif. 1996; 14: 136-145Crossref PubMed Scopus (51) Google Scholar], [3Lonnemann G. Assessment of the quality of dialysate.Nephrol Dial Transplant. 1998; 13: 17-20Crossref PubMed Scopus (38) Google Scholar]. To assess the growth of fungi and yeast in water and dialysate, malt extract agar (MEA) in combination with the culture conditions described previously in this article should be used. Water and dialysate samples have to be taken under aseptic conditions and stored in pyrogen-free tubes at 4 to 8°C. Samples should either be tested in the dialysis unit or be shipped to a specialized laboratory and assayed within 24 hours using the culture conditions outlined previously in this article and a quantitative Limulus amoebocyte lysate (LAL) test for the determination of endotoxin. The lower detection limit of the LAL assay should be at least 0.03 EU/mL. Finally, the time and site of sampling should be standardized. According to the DAfKN guidelines, reverse-osmosis water samples should be taken at different sites of the loop pipe using sterile connection sites after discarding 10 L of water. Dialysate samples should be taken at the end of a hemodialysis session from the dialysate tubing just before or after the dialyzer either by disconnection of the tubings from the dialyzer or by using sterile sampling sites in the dialysate tubings. The samples should be collected in pyrogen-free tubes after discarding 1 L of dialysate. During the last decade, several multicenter studies were performed to assess the microbiological quality of water and dialysate in the United States and Canada as well as in Europe[4Klein E. Pass T. Harding G.B. Wright R. Million C. Microbial and endotoxin contamination in water and dialysate in the central United States.Artif Organs. 1990; 14: 85-94Crossref PubMed Scopus (100) Google Scholar, 5Bambauer R. Schauer M. Jung W.K. Daum V. Vienken J. Contamination of dialysis water and dialysate: A survey of 30 centers.ASAIO J. 1994; 40: 1012-1016Crossref PubMed Scopus (74) Google Scholar, 6Laurence R.A. Lapierre S.T. Quality of hemodialysis water: A 7-year multicenter study.Am J Kidney Dis. 1995; 25: 738-750Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 7Arvanitidou M. Spaia S. Katsinas C. Pangidis P. Constantinidis T. Katsouyannopoulos V. Vayonas G. Microbiological quality of water and dialysate in all haemodialysis centres of Greece.Nephrol Dial Transplant. 1998; 13: 949-954Crossref PubMed Scopus (41) Google Scholar]. The results are summarized in Table 1. In comparison to the AAMI standards allowing a bacterial growth of 200 CFU/mL in water and 2000 CFU/mL in dialysate, these studies show that 7.4 to 35.3% of water samples and 11.7 to 36.3% of dialysate samples were out of compliance with the AAMI standards. Testing water and dialysate for endotoxin, up to 44% of samples contained more than 5 EU/mL of endotoxin. When the type of microorganisms were described in the most recent study performed in Greece[7Arvanitidou M. Spaia S. Katsinas C. Pangidis P. Constantinidis T. Katsouyannopoulos V. Vayonas G. Microbiological quality of water and dialysate in all haemodialysis centres of Greece.Nephrol Dial Transplant. 1998; 13: 949-954Crossref PubMed Scopus (41) Google Scholar], it is most disturbing that not only one third of the dialysate samples were contaminated with more than 2000 CFU/mL, but that 30% of these highly contaminated dialysate samples contained faecal coliforms (such as Escherichia coli), which had not been detected at all in the three other studies. It should be emphasized that only in the study conducted by Klein et al were adequate microbiological techniques with nutrient-poor culture agars (R2A) and prolonged incubation times at room temperature used[4Klein E. Pass T. Harding G.B. Wright R. Million C. Microbial and endotoxin contamination in water and dialysate in the central United States.Artif Organs. 1990; 14: 85-94Crossref PubMed Scopus (100) Google Scholar]. With this information in mind, one may speculate that bacterial growth is underestimated in the studies by Tokars et al[2Tokars J.I. Alter M.J. Miller E. Moyer L.A. Favero M.S. National surveillance of dialysis associated diseases in the United States-1994.ASAIO J. 1997; 43: 108-119PubMed Google Scholar], Bambauer et al[5Bambauer R. Schauer M. Jung W.K. Daum V. Vienken J. Contamination of dialysis water and dialysate: A survey of 30 centers.ASAIO J. 1994; 40: 1012-1016Crossref PubMed Scopus (74) Google Scholar], Laurence and Lapierre[6Laurence R.A. Lapierre S.T. Quality of hemodialysis water: A 7-year multicenter study.Am J Kidney Dis. 1995; 25: 738-750Abstract Full Text PDF PubMed Scopus (58) Google Scholar], and Arvanitidou et al[7Arvanitidou M. Spaia S. Katsinas C. Pangidis P. Constantinidis T. Katsouyannopoulos V. Vayonas G. Microbiological quality of water and dialysate in all haemodialysis centres of Greece.Nephrol Dial Transplant. 1998; 13: 949-954Crossref PubMed Scopus (41) Google Scholar] by a factor of up to 100.Table 1Microbiological quality of water and dialysate in the United States, Canada, and EuropeStudy (location)NBacterial growth % of samples above AAMI standardsaAAMI standards: water, 200 CFU/mL; dialysate, 2000 CFU/mLEndotoxin % of samples above 5 EU/mLKlein et al, 1990 (USA) Water15035.32 Dialysate15019.06Bambauer et al, 1994 (Germany) Water9017.812.2 Dialysate36011.727.5Laurence et al, 1995 (Canada) Water3547/1112b= for bacterial growth, N = 3547; for endotoxin N = 111231.844.0 Dialysatenot doneArvanitidou et al, 1998 (Greece) Water2557.4not done Dialysate25536.3not done(30% fecal coliform)a AAMI standards: water, 200 CFU/mL; dialysate, 2000 CFU/mLb = for bacterial growth, N = 3547; for endotoxin N = 1112 Open table in a new tab Taken together, bacterial contamination is an important problem in today's routine hemodialysis therapy. Nephrologists need to be aware of this problem and should test routinely, for example, once a month, the microbiological quality of the dialysis water in their units. If dialysate tests are done routinely, contaminated dialysis monitors can be identified and special procedures, including exchange of dialysate tubings and additional sterilization of the entire dialysate circuit using chemicals and heat, should be performed to decrease bacterial growth. Following such protocols, it is possible to control the bacterial contamination of dialysis water and dialysate and keep the quality within the recommended standards. Figure 1 shows the results of a single hemodialysis center in which decentralized production of dialysate from reverse-osmosis water and bicarbonate-buffered concentrate is performed. In 79% of the 62 dialysate samples, bacterial growth was below 200 CFU/mL. There was no sample containing more than 1000 CFU/mL, thus fulfilling the AAMI standards as well as the higher standards of the DAfKN. Lipopolysaccharides, also called endotoxins, are structural elements of the outer cell wall of gram-negative bacteria and are clearly the most important exogenous pyrogens present in contaminated dialysate. The intact LPS molecule and LPS fragments containing the lipid A subunit can be measured specifically by the LAL assay. In addition to LPS, there are more components of the bacterial cell wall such as peptidoglycans, fragments thereof such as muramyl-dipeptides, and other undefined substances as well as exotoxins, which are actively secreted from microorganisms (for example, exotoxin A of P. aeruginosa). None of these substances of bacterial origin are detected by the LAL assay. Their biological (and potentially pyrogenic) activity can be measured in a bioassay called cytokine-induction assay, because the main activity of exogenous pyrogens (bacterial products) is to induce the synthesis and release of endogenous pyrogens [cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α)] in blood monocytes and macrophages (mononuclear cells, PBMC). In the cytokine-induction assay, human donor PBMCs were incubated with samples containing an unknown amount of cytokine-inducing substances (CIS), for example, bacterial products in contaminated dialysate. During an 18- to 24-hour incubation, PBMCs produce and release cytokines such as IL-1β and TNF-α in response to CIS. Cytokines measured by quantitative immunoassays in PBMC cultures can be used as a readout of CIS present in the sample. The cytokine-induction assay is nonspecific but highly sensitive in measuring the CIS (= pyrogenic) activity in contaminated fluids such as dialysate. We and others have used the cytokine-induction assay to test the permeability of various dialyzer membranes to CIS derived from purposefully contaminated dialysate during in vitro dialysis experiments[8Lonnemann G. Bingel M. Floege J. Koch K.M. Shaldon S. Dinarello C.A. Detection of endotoxin-like interleukin-1-inducing activity during in vitro dialysis.Kidney Int. 1988; 33: 29-35Abstract Full Text PDF PubMed Scopus (124) Google Scholar, 9Lonnemann G. Behme T.C. Lenzner B. Floege J. Schulze M. Colton C.K. Koch K.M. Shaldon S. Permeability of dialyzer membranes to TNF alpha-inducing substances derived from water bacteria.Kidney Int. 1992; 42: 61-68Abstract Full Text PDF PubMed Scopus (158) Google Scholar, 10Laude-Sharp M. Caroff M. Simard L. Pusineri C. Kazatchkine M.D. Haefner-Cavaillon N. Induction of IL-1 during hemodialysis: transmembrane passage of intact endotoxins (LPS).Kidney Int. 1990; 38: 1089-1094Abstract Full Text PDF PubMed Scopus (157) Google Scholar, 11Evans R.C. Holmes C.J. In vitro study of the transfer of cytokine-inducing substances across selected high-flux hemodialysis membranes.Blood Purif. 1991; 9: 92-101Crossref PubMed Scopus (55) Google Scholar, 12Schindler R. Krautzig S. Lufft V. Lonnemann G. Mahiout A. Marra M.N. Shaldon S. Koch K.M. Induction of interleukin-1 and interleukin-1 receptor antagonist during contaminated in vitro dialysis with whole blood.Nephrol Dial Transplant. 1996; 11: 101-108Crossref PubMed Scopus (60) Google Scholar]. When microorganisms isolated from contaminated dialysate were grown in bicarbonate-buffered dialysate and a culture filtrate (0.45 μm filters) of this highly contaminated dialysate containing all relevant CIS was used to challenge dialyzer membranes, dialyzer membrane-dependent differences were observed. The most surprising but reproducible finding of these in vitro studies was that the low-flux cuprophan membrane was more permeable than some synthetic high-flux membranes (such as polyamide and polysulfone)[9Lonnemann G. Behme T.C. Lenzner B. Floege J. Schulze M. Colton C.K. Koch K.M. Shaldon S. Permeability of dialyzer membranes to TNF alpha-inducing substances derived from water bacteria.Kidney Int. 1992; 42: 61-68Abstract Full Text PDF PubMed Scopus (158) Google Scholar], [12Schindler R. Krautzig S. Lufft V. Lonnemann G. Mahiout A. Marra M.N. Shaldon S. Koch K.M. Induction of interleukin-1 and interleukin-1 receptor antagonist during contaminated in vitro dialysis with whole blood.Nephrol Dial Transplant. 1996; 11: 101-108Crossref PubMed Scopus (60) Google Scholar]. These results indicate that contaminated dialysate contains CIS of small molecular size (<5 kD), which are able to penetrate cellulosic low-flux membranes[8Lonnemann G. Bingel M. Floege J. Koch K.M. Shaldon S. Dinarello C.A. Detection of endotoxin-like interleukin-1-inducing activity during in vitro dialysis.Kidney Int. 1988; 33: 29-35Abstract Full Text PDF PubMed Scopus (124) Google Scholar]. However, why are some high-flux membranes with higher ultrafiltration coefficients and a higher membrane cutoff (approximately 30 to 40 kD) less permeable than low-flux cuprophan? Subsequent studies revealed that three important characteristics of the dialyzer membrane influence the degree of pyrogen-permeability of the membrane: First, the membrane polymer is able to adsorb bacteria-derived CIS in contaminated dialysate. Many CISs such as LPS and lipid A-bearing LPS fragments are hydrophobic because they are rich in lipids. These hydrophobic substances can be adsorbed by hydrophobic surfaces. In contrast to the entirely hydrophilic cellulosic membranes such as low-flux cuprophan, Hemophan, and high-flux cellulose diacetate and triacetate, the synthetic membranes polyamide and polysulfone consist of a copolymer bearing hydrophilic as well as hydrophobic domains on the surface. These synthetic polymers adsorb CIS to the hydrophobic domains caused by hydrophobic interaction. Second, an important difference is the membrane thickness[9Lonnemann G. Behme T.C. Lenzner B. Floege J. Schulze M. Colton C.K. Koch K.M. Shaldon S. Permeability of dialyzer membranes to TNF alpha-inducing substances derived from water bacteria.Kidney Int. 1992; 42: 61-68Abstract Full Text PDF PubMed Scopus (158) Google Scholar]. The thickness of cellulosic low-flux membranes is only 6.5 to 8 μm, whereas that of synthetic membranes is approximately 35 to 50 μm. The membrane thickness determines, in part, the diffusive resistance of the dialyzer membrane. Because diffusion seems to be the predominant transport mechanism of CIS across the dialyzer membrane, a thicker membrane will be less permeable than a thin membrane. The synthetic membranes consist of two components: a thin skin-like surface on the blood side of the hollow fibers that is supported by a thick sponge-like porous structure. Coming from the dialysate side, CIS first enter the support structure in which adsorption to hydrophobic membrane domains is very likely. Finally, the third mechanism involved in pyrogen permeability is the formation of a second layer of plasma proteins on the dialyzer membrane facing the blood side, a mechanism called protein coating. It has been shown that protein coating is more pronounced on polysulfone membranes than on cellulose triacetate membranes[13Lonnemann G. Schindler R. Lufft V. Mahiout A. Shaldon S. Koch K.M. The role of plasma coating on the permeation of cytokine-inducing substances through dialyser membranes.Nephrol Dial Transplant. 1995; 10: 207-211Google Scholar]. In the same study, we could show that protein coating reduces significantly the pyrogen permeability of polysulfone membranes. In summary, these in vitro studies demonstrate that the ability of the membrane polymer to adsorb CIS either by direct interactions between hydrophobic membrane domains and CIS or by formation of a CIS-adsorbing protein layer caused by protein coating is more important than the pore size of the membrane in order to reduce pyrogen permeability. Based on the extraordinary pyrogen-adsorbing capacity in the presence of high water permeability, synthetic polyamide and polysulfone high-flux membranes have been introduced as pyrogen filters to produce ultrapure and pyrogen-free dialysate and substitution fluid in online treatment modalities. In vivo studies were performed to test whether standard hemodialysis with moderately contaminated bicarbonate dialysate fulfilling the recommended microbiological standards in combination with pyrogen-permeable dialyzer membranes results in increased cytokine production in chronic hemodialysis patients. In a first approach, 11 end-stage renal disease (ESRD) patients on chronic hemodialysis with low-flux cuprophan dialyzers were studied in an A-B/B-A crossover design with standard bicarbonate dialysate (A) or ultrafiltered bicarbonate dialysate (B)[14Schindler R. Lonnemann G. Schäffer J. Shaldon S. Koch K.M. Krautzig S. The effect of ultrafiltered dialysate on the cellular content of interleukin-1 receptor antagonist in patients on chronic hemodialysis.Nephron. 1994; 68: 229-233Crossref PubMed Google Scholar]. Four patients started with period A followed by period B, the remaining seven patients started with ultrafiltered dialysate (B) and switched to unfiltered dialysate (B). Ultrafiltration of dialysate was done using polysulfone F80 high-flux dialyzers (Fresenius, Heidelberg, Germany). Study periods of eight weeks each with determination of dialysate bacteriology and endotoxin levels every two weeks were performed. Blood samples were taken after the long interdialytic interval immediately before start of the hemodialysis session at least three to six times per period and patient. PBMCs were separated from blood by Ficoll Hypaque centrifugation, washed, resuspended in tissue culture medium in a concentration of 2.5 × 106 PBMC/mL, and frozen at -70°C. After three thaw-freeze cycles, cell-associated IL-1 receptor antagonist (IL-1Ra) was measured by specific radioimmunoassay in PBMC lysates as a marker of in vivo activation of PBMCs in ESRD patients[14Schindler R. Lonnemann G. Schäffer J. Shaldon S. Koch K.M. Krautzig S. The effect of ultrafiltered dialysate on the cellular content of interleukin-1 receptor antagonist in patients on chronic hemodialysis.Nephron. 1994; 68: 229-233Crossref PubMed Google Scholar]. PBMC-IL-1Ra concentrations were averaged per patient and study period. The results are shown in Figure 3. Bacterial growth was 148 (range 61 to 400) CFU/mL in standard dialysate (period A) and 0 CFU/mL in period B with ultrafiltered dialysate. The endotoxin concentrations were 80 (range 14 to 10,000) pg/mL [0.40 (0.07 to 2.0) EU/mL] in unfiltered dialysate and 2 (0 to 4) pg/mL (0.01 EU/mL) in ultrafiltered dialysate. Compared with period A, the IL-1Ra content in PBMCs was decreased in 10 out of 11 patients in period B using ultrafiltered dialysate. The group mean of PBMC-IL-1Ra dropped significantly (P < 0.02) when standard dialysate was replaced by ultrafiltered dialysate Figure 2[14Schindler R. Lonnemann G. Schäffer J. Shaldon S. Koch K.M. Krautzig S. The effect of ultrafiltered dialysate on the cellular content of interleukin-1 receptor antagonist in patients on chronic hemodialysis.Nephron. 1994; 68: 229-233Crossref PubMed Google Scholar].Figure 2Content of interleukin 1 receptor antagonist (IL-1Ra) in peripheral blood mononuclear cells (PBMCs) isolated from the same end-stage renal disease (ESRD) patients (N = 11) on low-flux cuprophan hemodialysis with ultrafiltered dialysate (right) or nonfiltered dialysate (left). The symbols represent the mean of three to six measurements. The horizontal bars indicate the group means (P < 0.02).View Large Image Figure ViewerDownload (PPT) In a second study of similar cross over design, nine ESRD patients were studied during two study periods of eight weeks each. Standard, nonfiltered bicarbonate dialysate was used throughout the study. Bacterial growth was 159 (range 22 to 600) CFU/mL, and the dialysate endotoxin concentration was 36 (3 to 142) pg/mL [0.18 (0.015 to 0.72) EU/mL]. Hemodialysis was performed either with low-flux cuprophan dialyzers (period A) or with high-flux polysulfone F60 dialyzers (period B). Five patients started with cuprophan followed by F60 dialyzers, and the remaining four patients started with high-flux F60 and then switched to low-flux cuprophan. Repeated measurements of IL-1Ra in PBMC lysates were averaged per patient and study period. Results are shown in Figure 3. PBMC-IL-1Ra content dropped in eight out of nine patients when the pyrogen-permeable low-flux cuprophan dialyzers were replaced by pyrogen-adsorbing high-flux polysulfone F60 dialyzers. Comparing the two study period" @default.
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• W2072138214 date "2000-08-01" @default.
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• W2072138214 title "The quality of dialysate: An integrated approach" @default.
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