Dialysate Purifaction
reactive toHemodialysis patients are at risk of injury from chemical and microbiological contaminants in the dialysate. To avoid injury from these contaminants, the water and concentrates used to produce dialysate, as well as the dialysate itself, are required to meet well-established quality standards .
Compliance with these standards has largely eliminated acute adverse events resulting from dialysate contamination.
For this reason, the use of dialysate of much higher microbiological purity than is required has been recommended for routine hemodialysis. This "ultrapure" dialysate is commonly defined as :
1-Having a bacterial count less than 0.1 CFU/ ml and
2-An endotoxin content less than 0.03 EU/mL measured by the Limulus amebocyte lysate assay .
Use of ultrapure dialysate is required for High Flux dialysis and on-line hemodiafiltration , where dialysate is used to prepare the substitution solution.
 
1. The key for the endotoxin retention filter
The contamination of water and dialysate with bacterial endotoxin and its fragments was a neglected problem in hemodialysis for many years ( 1 ).
In the mid- 1980s, the Association for the Advancement of Medical Instrumentation (AAMI) restricted the bactenial contamination of pure water used for the preparation of dialysate to 200 CFU/mL and the bacterial contamination of dialysate to a maximum of 2000 CFU/mL (2). Epidemiological studies in 51 U.S. Hemodialysis centers revealed that 35.3% of the water samples and 19% of the dialysate samples were not in compliance with the AAMI standards. There was no correlation observed between the type of water purification system and the frequency of disinfection of the system and the levels of bacterial or endotoxin contamination.
Furthermore, yeast and fungi were found in the dialysate of 30% and 70% of the centers, respectively (3). Kulander et at. reported that 49% of 39 dialysis units in Sweden had endotoxin levels higher than 25 ng/L in the dialysate whereas 18% of the units had high levels of endotoxin of more than 100 ng/L (4).
In consequence, unexplained febrile reactions during and after hemodialysis have been linked to endotoxin contamination of dialysate. The incidence of febrile reactions did not change markedly during the past 20 years even though water preparation has been improved by the use of reverse-osmosis filters and better controls of water quality in most dialysis centens. Optimal quality of purified water cannot prevent bacterial and endotoxin contamination of dialysate because concentrates containing bicarbonate may have bacterial contamination of up to several hundred- thousands CFU/mL, resulting in similar contamination of the bicarbonate dialysate (5). Furthermore, bacterial growth-in particular, of Pseudomonas aeruglnosa-frequently occurs within the dialysis machine during dialysate preparation. Some authors also reported specific antibody formation in dialysis patients after Pseudomonas contamination of dialysate (6).
During high-flux hemodialysis. Several liters of dialysate fluid were backfiltered into the blood compartment. Such backfiltration implicates an increased convective transfer of compounds with a molecular weight of up to around 20000 d, which may further increase the risk of bacterial and endotoxin contamination of dialysate. The problem can be solved only by prevention of endotoxin transfer from dialysate into the patient. For that reason, there has been demand for a minimal permeability for endotoxin in dialyzers. Compared with membranes of regenerated cellulose, synthetic membranes, such as AN 69, polysulfone, and polyamide seemed to have a lower endotoxin permeability. The lowest endotoxin transfer was found across polyamide and polysulfone membranes (7).
Furthermore, the use of sterile dialysate has been recommended. Sterile filtration was performed by polyamide or more frequently by polysulfone filters containing standard high-flux membranes. Several studies indicated that dialysate contains no or very small amounts of endotoxin after filtration through a standard polysulfone high-flux membrane (5,8-10).
Cytokine Inducing substances (CIS)
Hemodialysis patients are at risk of injury from chemical and microbiological contaminants in the dialysate. To avoid injury from these contaminants, the water and concentrates used to produce dialysate, as well as the dialysate itself, are required to meet well-established quality standards . Compliance with these standards has largely eliminated acute adverse events resulting from dialysate contamination.
Long-term morbidity from exposure to chemical contaminants in the dialysate is also rare, providing the water and concentrates used to prepare dialysate are of the requisite quality. However, preventing long-term morbidity from exposure to microbiological contaminants is more difficult.
Because the chlorine compounds used to suppress bacterial growth in the potable water supply are removed when the water is treated for hemodialysis, it is almost impossible to completely prevent bacterial proliferation in the treated water and the dialysate. As a result, even though conventional dialysate meets the required quality standards, it usually contains some low level of microbiological contamination, including fragments of endotoxin, peptidoglycans, and fragments of bacterial DNA. These contaminants, sometimes collectively referred to as "cytokine-inducing substances," cross both low-flux and high-flux hemodialysis membranes [11] and stimulate cytokine production by inflammatory cells [12].
Plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in many hemodialysis patients, suggesting a state of chronic inflammation [13]. This inflammatory state may be an important contributor to the long-term morbidity associated with hemodialysis . While inflammation appears to be a consequence of chronic kidney disease, per se , aspects of the hemodialysis procedure, including low levels of microbiological contaminants in the dialysate, may also act as inflammatory stimuli .
For this reason, the use of dialysate of much higher microbiological purity than is required has been recommended for routine hemodialysis [14]. This "ultrapure" dialysate is commonly defined as :
1-having a bacterial count less than 0.1 CFU/ml and
2-an endotoxin content less than 0.03 EU/mL measured by the Limulus amebocyte lysate assay [14].
Use of ultrapure dialysate is required for on-line hemodiafiltration and hemofiltration, where dialysate is used to prepare the substitution solution [15].
References :
J, Ritz E: Water quality-A neglected problem in hemodialysis. Nephron l987;46: 1-6.
2. AAMI (Association for the Advancement of Medical Instrumentation). RD5 Hemodialysis Systems. 2nd Ed. New York: American National Standard Institute; 1992.
3. Klein E, Pass T, Harding GB, Wright R, Million C: Microbial and endotoxin contamination in water and dialysate in the central United States. ArtifOrgans 1990;
14:85-94.
4. Kulander L, Nisbeth U, Danielsson BG, Eriksson 0: Occurrence ofendotoxin in dialysis fluid from 39 dialysis units. J Hosp Infect 1993;24:29-37.
5. Pegues DA, Oettinger CW, Bland LA, et at.: A prospective study of pyrogenic reactions in hemodialysis patients using bicarbonate dialysis fluids filtered to remove
bacteria and endotoxin. J Am Soc Nephroi 1992;3: 1002- 1007.
6. Yioshioka T, Ikegami K, Ikemura K, et at.: A study on limulus amebocyte lysate (LAL) reactive material derived from dialyzers. Jpn J Sung 1989;19:38-4l.
7. Lonnemann G: Dialysate bacteriological quality and the permeability of dialyzer membranes to pyrogens. Kidney int 1993;43lSuppl 411:195-200.
8. Capelli G, Tetta C, Cornia F, et at.: Removal of limulus reactivity and cytokine-inducing capacity from bicarbonate dialysis fluids by ultrafiltration. Nephrol Dial Transplant 1993;8: 1133-1139.
9. Gault MH, Duffet AL, Murphy JF, Purchase LH: In search ofstenile, endotoxin-free dialysate. ASAIO J 1992; 38:M43 1-M435.
10. Fninak S, Polaschegg 1W, Levin NW, Pohiod DJ, Dumler F, Saravolatz LD: Filtration of dialysate using an on-line dialysate filter. Int J ArtifOrgans 1991;14:691-697.
11-Schindler, R, Beck, W, Deppisch, R, et al. Short bacterial DNA fragments: detection in dialysate and induction of cytokines. J Am Soc Nephrol 2004; 15:3207.
12-Lonnemann, G, Behme, TC, Lenzner, B, et al. Permeability of dialyzer membranes to TNF alpha-inducing substances derived from water bacteria. Kidney Int 1992; 42:61.
13-Owen, WF, Lowrie, EG. C-reactive protein as an outcome predictor for maintenance hemodialysis patients. Kidney Int 1998; 54:627.
14-European Renal Association — European Dialysis and Transplant Association. European Best Practice Guidelines for Haemodialysis (Part I), Section IV: Dialysis fluid purity. Nephrol Dial Transplant 2002; 17:45.
15-Ledebo, I. On-line preparation of solutions for dialysis: practical aspects versus safety and regulations. J Am Soc Nephrol 2002; 13 Suppl 1:S78.

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