|Year : 2001 | Volume
| Issue : 3 | Page : 325-326
|Monitoring the Microbial Purity of the Treated Water and Dialysate
Bernard Canaud1, Katja Martin1, Marion Morena2, Jean-Yves Bosc2, Helene Leray-Moragues1, Monji Mahowashi3, Frank Stec4, Sylvie Hansel3
1 Department of Nephrology and Renal Research and Training Institute, Lapeyronie University Hospital, Montpellier, France
2 Department of Nephrology, Lapeyronie University Hospital, Montpellier, France
3 Department of Pharmacy, Lapeyronie University Hospital, Montpellier, France
4 AIDER, Rue de Lacroix Lavit Montpellier, France
Click here for correspondence address and email
| Abstract|| |
Dialysate purity has become a major concern in recent years since it has been proven that contamination of dialysate is able to induce the production of proinflammatory cytokines, putatively implicated in the development of dialysis related pathology. In order to reduce this risk, it is advised to use ultrapure dialysate as a new standard of dialysate purity. Ultrapure dialysate preparation may be easily achieved with modern water treatment technologies. The reliable production of ultrapure dialysate requires several prerequisites: use of ultrapure water, use of clean electrolytic concentrates, implementation of ultrafilters in the dialysate pathway to ensure cold sterilization of the fresh dialysate. The regular supply with such high-grade purity dialysate relies on predefined microbiological monitoring of the chain using adequate and sensitive methods, and hygienic handling including frequent disinfection to reduce the level of contamination and to prevent biofilm formation. Reliability of this process requires compliance with a very strict quality assurance process. In this paper, we summarized the principles of the dialysate purity monitoring and the criteria used for surveillance in order to establish good antimicrobial practices in dialysis.
Keywords: Dialysate purity, Microbial contamination, Dialysate microbiological standard, Hemocompatibility, Quality assurance.
|How to cite this article:|
Canaud B, Martin K, Morena M, Bosc JY, Leray-Moragues H, Mahowashi M, Stec F, Hansel S. Monitoring the Microbial Purity of the Treated Water and Dialysate. Saudi J Kidney Dis Transpl 2001;12:325-6
|How to cite this URL:|
Canaud B, Martin K, Morena M, Bosc JY, Leray-Moragues H, Mahowashi M, Stec F, Hansel S. Monitoring the Microbial Purity of the Treated Water and Dialysate. Saudi J Kidney Dis Transpl [serial online] 2001 [cited 2016 May 27];12:325-6. Available from: http://www.sjkdt.org/text.asp?2001/12/3/325/33556
| Introduction|| |
Over the last decade, microbial contamination of dialysate has become a major concern in hemodialysis.  In the late 80's, dialysate purity was mainly targeted to prevent pyrogenic reactions associated with the use of bicarbonate buffer and highly permeable membranes. ,,,,
Since the late 90's, the dialysate purity has been considered as the main factor in the complex hemocompatibility network. ,, The use of contaminated dialysate fluid has similar effects to the use of complement activating membranes. , Both are shown to be responsible for repetitive subclinical inflammatory reactions. ,,, To prevent dialysate-related microinflammation it has been suggested to use dialysate with a microbiological quality of an intravenous pharmaceutical solution. , For this purpose, the ultrapure dialysate concept was introduced.  Ultrapure dialysate (UPD) standardizes a sterile and non-pyrogenic dialysate produced by cold sterilization using ultrafilters. ,,,,
Several reports have outlined the beneficial effects of using ultrapure dialysate in regular dialysis. ,,, It has been confirmed from in vitro laboratory experiments that the use of UPD was able to prevent cell activation and to reduce the production and/or release of proinflammatory cytokines.  Clinical studies have shown that long-term use of UPD is associated with a significant reduction of incidence of the β2M-amyloidosis, , prevention of chronic inflammation in hemodialysis patients,  suppression of hemodialysis related pyrogenic reactions  and reduced consumption of erythropoietin.  In the overall perspective of improving dialysis quality, presenting the unphysiological effect of dialysis as well as reducing the blood-dialysis interaction (hemoincompatibility), it seems quite desirable to use "low-complement activating" membranes and ultrapure dialy sate. , Regular use of UPD is affordable with the utilization of modern water treatment systems and optimally designed hemo-dialysis proportioning machines. ,, However, it must be kept in mind that the dialysate production is a complex chain and the microbial purity of the final dialysate integrates the efficacy of different components and depends directly on the worst functioning component of this chain. The regular production of UPD in a dialysis facility relies on several options: a perfectly designed water treatment and distribution system, an adequately designed proportioning machine including a dialysate ultrafilter module, the use of sterile electrolytes concentrate solution and on very stringent hygienic standards integrated in a continuous quality assurance process. ,
Over the last few years, it has been recognized that ultrapure dialysate may become a new quality standard for contemporary dialysis. , Indeed, some confusion still persists on how the fluid purity should be defined and evaluated in clinical dialysis practice.  This is partly due to the flawed and vague definition of the pharmaceutical guidelines and standards used in hemodialysis.
The purpose of this report is threefold: firstly, we review currently used standards of water and dialysate fluid in hemodialysis, secondly, we summarize the important technical issues to easily achieve high dialysate purity; thirdly, we define a schedule for microbiological monitoring of water and dialysate in hemodialysis.
| Standards for water and dialysate fluid|| |
The antimicrobial standards for water and dialysate fluids were first developed by the Association for the Advancement of Medical Instrumentation (AAMI). The AAMI standard sets the upper limit of bacteria in water at 200 colony forming units per ml (CFU/ml) and in dialysate at 2000 CFU/ml.  The count of bacteria is to be obtained by spreading 0.5 ml fluid sample on a plate containing media made of trypticase soy agar (TSA). The number of colonies is counted after 48 hours incubation time at 37°C. No standard was defined for endotoxin levels in their first edition while the last edition sets the upper limit to 2 EU/ml. Indeed, this standard was followed worldwide. Meanwhile, several countries developed their own microbiological standards to improve dialysis quality and/or to facilitate the implementation of new dialysis options (high flux dialysis, on-line hemodiafiltration and hemofiltration modalities). The AAMI standards were, also, revised in the year 2000 to comply with the dialysis purity needs.
The International Standards (ISO) recently reported are in agreement with those of the AAMI: setting total viable microbial count for water to an upper limit of 200 CFU/ml and for endotoxins (LAL) of 5 EU/ml,  .
The European Pharmacopoeia (EP) has defined more stringent standards for the microbial purity of water and dialysate. In fact, no difference is made between water and dialysate. The upper limit of bacteria in water and dialysis fluids is set at 10 2 CFU/ml and endotoxin at 0.03 EU/ml.  Some countries (Germany, Sweden, France, Holland) have reinforced these recommendations and detailed more precisely the method for sampling and culturing. Such constraints were made in order to increase the sensitivity of the microbiological monitoring and/or, at best, evaluate the microbial risk associated with specific dialysis modalities producing on-line substitution fluid.
Different water and dialysate microbial purity grades may be defined according to the level of bacteria contamination and content of endotoxins. They are summarized in the [Table - 1],[Table - 2]. Regular water and dialysate used for conventional hemodialysis should comply with the EP standard (<10 2 CFU/ml, ET <0.25 EU/ml), while ultrapure water and dialysate indicated for highly biocompatible dialysis should achieve higher level of microbial purity (<10 -1 CFU/ml, ET <0.03 EU/ml). Sterile water and dialysate fluids rely on the success achieved by a series of several sterilizing filters. Addition of sterilizing ultrafilters virtually abolishes the risk of failure and permits the safe on-line production of sterile and non-pyrogenic dialysis fluid.
Most recent surveys performed on water and/or dialysate microbiological quality in dialysis facilities either in the US or in Europe have shown that compliance with the rather weak AAMI standards was achieved in two-thirds of the dialysis facilities. ,,,, In contrast, the nephrology community recognizes ultrapurity of water and dialysate as being beneficial for ESRD patients and accepts it as a new standard for highly biocompatible dialysis. Therefore, all efforts should be made to achieve the basic standards of dialysate microbial purity. ,
| Technical considerations of the dialysate chain production|| |
Dialysate is the liquid medium flowing countercurrent through the artificial kidney permitting the solute exchange with patient's blood accross a semi-permeable membrane during a dialysis session. It is an electrolytic solution made from purified water, electrolytes concentrate mixed up to a fixed proportion by a dialysis machine. From a very basic consideration, the microbial contamination of the dialysate has three potential sources: first, the water treatment system, second, the electrolytic concentrates, and third, the dialysis proportioning dialysis machine.
| Water treatment system|| |
Contemporary dialysis requires the use of highly purified water.  Water contaminants (particulates, dissolved substances) including microorganisms should be removed. The complexity and cost of the water treatment system will differ according to the desired grade of water purity.
Conventionally purified water (complying with EP standard) is easily obtained from a simple water purification system made of a pretreatment softener, activated carbon, downsizing microfilters and a reverse osmosis (RO) module assembled in series.
Ultrapure water may be used on regular basis in all kinds of dialysis modalities. It is a basic prerequisite of renal replacement modalities using on-line production of substitution fluid in hemodiafiltration and hemofiltration. Several technical options and arrangement may be used to reach this goal. To ensure a consistent production of high-grade quality water, it is necessary to optimize the design of the water purification system. This is a major task for water engineering to find the best assembly of the different components (microfilters, softener, reverse osmosis) in terms of size (volume, treatment capacity) and position in the chain. Usually, a combination of (water pretreatment) two RO modules in series and a direct delivery loop (no water tank) is the best configuration to preserve the microbiologic quality of treated water. Another option is to "polish" the pretreated water via RO module and deionizer module (resin beds or electrochemical deionizer) in series. To prevent bacterial contamination and/or proliferation, the technicalities of the water distribution circuit form a critical point. Nature of the material used (PVC, Polyurethane, Stainless steel), inner diameter (reduced internal diameter) and high flow rate in the tubing network (increasing the "shear stress") greatly impact the results of the system. It is important to underline that great effort should be made to obtain the best plumbing for the water distribution loop, with a linear pipe configuration favoring continuous high speed water circulation, preventing water stagnation and contamination, and avoiding dead space and lateral arms.
Hygienic handling rules are mandatory to disinfect the water treatment system and to prevent the formation of biofilm. The maintenance of a water treatment system requires adequate measures including frequent disinfection cycles (either chemical or heat or mixed) of the complete chain filter and resin changes according to the size and the contamination level and prevention of microbial biofilm formation in the circuit. Although, it seems virtually impossible to establish common rules, it is easy to claim that any water treatment system must be disinfected regularly. An optimal periodicity of disinfection is difficult to define and depends on the degree and kinetics of contamination after disinfection. Generally, it is recommended to completely disinfect the water treatment system once per month.
| Electrolytic concentrates|| |
The main source of microbial dialysate contamination is often the bicarbonate solution, which favours bacterial growth. Originally, electrolyte concentrates were provided as liquids in two independent plastic containers (A for acid; B for bicarbonate) and were reconstituted into dialysate by the dialysis machine. Nowadays, bicarbonate is mainly distributed as a soluble powder, which is diluted to a saturated solution by the dialysis machine. Soluble bicarbonate powder reduces the risk of bacterial contamination. Addition of dextrose to the acid concentrate may be another factor favoring bacterial growth in the dialysate. It is strongly recommended to only use sterile concentrates to reduce the risk of bacterial dialysate contamination. Bacterial contamination may occur at the time of opening the plastic container and introducing the sampling rod. The sampling rod must be kept clean and should be regularly disinfected to reduce the risk of contaminating the concentrate.
Proliferation of bacteria can take place during the length of the dialysis session favoured by the bicarbonate salt. Closing the container cap is mandatory to reduce both airborne bacterial contamination and proliferation. Bicarbonate must be stored at low temperatures to prevent bacterial growth.
| Hemodialysis proportioning machine|| |
Hemodialysis machines offer an excellent seeding media for bacteria and dialysate contamination. Several factors such as the design of the circuit of the machine and inadequate disinfection procedures may favour bacterial growth and biofilm formation in the hydraulic circuit. Hygienic maintenance of all the hemodialysis delivery machines is required to ensure the dialysate purity. That includes regular cleaning of the hydraulic tubing with a detergent to remove the organic deposits, descaling with acid solution to dissolve phosphate and calcium precipitates and disinfecting with an appropriate chemical sterilizing agent and/or heat. Replacement of the hydraulic tubing is advised in case of a high contamination and/or biofilm formation in the dialysis circuit. In all cases, cleaning, descaling and disinfection must comply with the recommendations of manufacturers in order to prevent material damages and assure efficiency.
Dialysate ultrafiltration is the only method that has been proven to be efficient in routine clinical use to guarantee the ultrapurity of the dialysate reaching the dialyser. , Safety of the cold sterilizing process relies on the addition of those ultrafilters.  Two ultrafilters placed in series appear to be an optimal number to warrant an absolute safety for "cold sterilization".
A precise microbial inventory of the machine as well as a comprehensive hydraulic scheme is required to define disinfection procedures and their frequency. Regular microbiologic dialysate monitoring is necessary to optimize the disinfection cycles and to check their efficacy. 
Renal replacement therapies using on-line production of substitution fluid (hemofiltration and hemodiafiltration) require more stringent maintenance rules. , Disinfection, either by heat or chemical agents, must be performed after each dialysis session. Cleansing and descaling of the hemodialysis proportioning machine should be performed on a daily basis. The on-line production of substitution fluid for hemodiafiltration or hemofiltration requires the use of certified hemodialysis proportioning machine equipped with an ultrafiltration module made of two ultrafilters on the inlet of the dialysate pathway.
| Microbiological monitoring of water and dialysate|| |
Monitoring of water and dialysate contamination should rely on the most sensitive methods of microbiological quantification.  These methods are far more advanced than those recommended in the international standards.  The basic principle for microbiological quantification (bacteriometry concept) is to provide ideal conditions to each living microorganism in water and dialysate to grow in a discrete colony that can be identified and counted visually. The result is then expressed as number of colonies forming unit (CFU) per milliliter of fluid cultured (CFU/ml).
The optimal growth conditions for waterborne bacteria are different from the usual patients' environment (e.g. blood-borne). Gram-negative strain bacteria living in water and dialysate require relatively poor nutrient media (R2A, TGEA) incubation at ambient temperature (20-22°C) and prolonged time of observation (7 to 14 days). Accordingly, the usual growth conditions recommended by AAMI-ISO standard, rich medium (TSA), body temperature (37°C) and short time of observation create unfavorable conditions for these bacteria.  Bacteriometry obtained in these conditions provide optimistic results with low contamination. It is easily shown that the same sample (water and/or dialysate) proceed with the optimized method (poor nutrient media, ambient temperature, long period of observation) will show two logs more CFU than the sample cultured with AAMI method. Such discrepancies in water and dialysate bacteriometry have been clearly demonstrated in several scientific studies to be accepted as reference method. , The objective of the microbiological quantification is to obtain the reproducible and true picture of dialysate contamination; therefore, it is highly recommended to use the most sensitive method. It is also important to note that in this approach only living bacteria will be quantified, underlying the fact that the true contamination may be underestimated due to the presence of killed bacteria.
| Endotoxin monitoring of water and dialysate|| |
Endotoxins in the dialysate result from the presence of water-borne bacteria. Since endotoxins are a part of the cell wall of the bacteria, it was thought that their detection by specific endotoxin assays could be used instead of bacterial count. However, several studies reported disapponiting results showing the lack of correlation between the degree of bacterial contamination (CFU) and the endotoxin content (EU) measured by limulus amaebocyte lysate assay (LAL). Several explanations have been given for this apparent discrepancy: some bacterial strains not producing endotoxins, presence of bacteria releasing exotoxins, bacteria releasing muramyl dipeptides from the cell wall, and aggregation of endotoxins preventing their reaction with the LAL.
Extremely sensitive methods have been proposed to detect non-endotoxin cytokines-inducing substances.  These methods, which are based on bloodmonocytes activation, require skilful and expert laboratories. Cytokine assays are recognized as the most sensitive mean to detect endotoxin presence in dialysis fluid. Nevertheless, they are currently used for scientific purposes but are not routinely applicable in dialysis.
The LAL assay is still the most appropriate assay to detect the presence of endotoxins in dialysis fluid.  Simplified LAL gel clot method offers a threshold sensitivity level of 0.03 EU/ml. More sensitive methods have been proposed,which are based on a kinetic LAL dilution assay increasing the sensitivy of detection to 0.001 EU/ml.
A new method using silkworm larvae plasma has been reported to detect peptidoglycan substances, not detected by the LAL, with a very low threshold.  This interesting assay is still recognized as complementary to the LAL for detecting potential proinflammatory cytokine inducing substances.
| Quality assurance process|| |
The regular production of highly purified water and/or dialysate relies on a global quality assurance process. Expressed differently, all persons working in a dialysis unit (technician, nurse, pharmacist, microbiologist, physician) should be involved in the quality assurance process. Disinfection and maintenance protocols should be applied and their efficacy checked. Microbiological monitoring (bacteriometry, endotoxins quantification) is obligatory and results should be used to establish corrective strategies.
Periodic disinfection of the water treatment system and dialysis proportionning machine should be performed according to the levels and the kinetic of bacterial contamination.  The type of disinfectant, concentration and time of exposure should comply with the manufacturer recommendations. Combined procedures aiming for descaling and disinfection are quite desirable.
Periodicity of water and dialysate sampling is a crucial part of the microbiological monitoring. It seems advisable to check the microbial purity of water and dialysate every month. Such surveillance is the only means to have a representative picture of the dialysate purity. It is also important to mention that every dialysis proportionning machine should be checked monthly. More frequent sampling should be performed in case of febrile outbreaks. Furthermore, samples should be obtained after every intervention on the water treatment system or on the dialysis machine.
Water sampling sites are usually placed at crucial points of the dialysate chain production: on the tap water, after softener, before and after the reverse osmosis module and at the dialysis machine entrance (water distribution loop). Specific sampling port valves, made of stainless steel, are to be used. At the time of water collection, sampling ports should be flame disinfected. Between the intervals, sterile containers should be used to protect the sampling valves. Water should be collected (100 ml) in sterile glass containers in a free-flow manner after 5 to 10 liters have been discarded. The dialysate sample sites are installed on the effluent dialysate pathway of the dialysis machine. Half to one liter of dialysate should be discarded from each port before 100 mls of effluent dialysate are collected. The time for transport and storage of samples should be as short as possible (less than 30 minutes). The glass containers should be stored at 4-8°C in a refrigerator and analysis of the samples should be performed in the appropriate laboratory within 24 hours.
The microbiology screening tests include culturing of water and dialysate samples for precise bacteriometry (CFU/ml). Sensitive methods based on filtering 100 ml of the sample through a 0.45-0.22 µm membrane and culturing the membrane on a poor nutrient medium (R2A, TGEA) are prefered.  For fungi and yeast, a different medium based on malt extract agar (MEA) is suitable. Alternatively, when these methods are not available, conventional bacterial count obtained from culturing the fluid sample on a plate medium can be used. In all cases, the culture medium used should be poor (R2A, TGEA) if incubated at ambiant temperature for seven days.  Endotoxin content in dialysis fluid should be determined by the kinetic LAL assay dilution with a threshold detection limit of 0.001 EU/ml. If the kinetic LAL assay is not availabe, the use of the LAL gel clot method with a threshold limit at 0.03 EU/ml will be advisable.
The follow-up of the hemodialysis patient is crucial in this context. Clinical assessment and regular body temperature monitoring are mandatory. Periodic followup of the inflammatory sensitive markers are quite advisable. C-Reactive protein (CRP) is for this purpose a very sensitive marker able to detect chronic microinflammation in dialysis patients.  CRP may be used as a surrogate of monitoring the pro-inflammatory cytokine production related to the dialysate microbial contaminants. 
The microbiological results obtained from this surveillance (water and dialysate) must be stored in an appropriate database and utilized to guide disinfection schedules.  Regular reports of bacteriometry and endotoxins content for a dialysis unit are also important markers that may be used to confirm the treatment quality has be achieved.
Specific corrective actions must be undertaken if the regular microbiological assessment detects contamination levels above the aimed threshold limits. Several measures are proposed, including the reinforcement of hygienic measures such as descaling, cleaning and disinfecting the different parts of the water treatment system including the dialysis machine. Combined disinfection procedures (chemical, thermal, or mixed) and periodicity of cycles (weekly, monthly for example) must be advised when the level of the microbial contamination is not satisfactory.  One must be alert to the possibility that rapid increase of the bacterial count in the water or the dialysate after a disinfection cycle may indicate a significant formation of biofilm. ,, In this case it is mandatory to replace the infected hydraulic tubing parts of the water treatment system or the dialysis proportionning machine.
In conclusion, ultrapure water and dialysate are new standards for a more biocompatible dialysis system. The production of ultrapure dialysate relies on a quality assurance process. The microbiological quantification monitoring is an essential part of this program. Sensitive methods and frequent analysis are the only means to ensure a correct microbiological quantification. Very strict hygienic protocol should be integrated in a global water and dialysate vigilance plan. Disinfection procedures (chemical, thermal, mixed) and periodicity of cycles (weekly, monthly for example) must be adapted to the level and the kinetics of the microbial contamination.
| References|| |
|1.||Klein E, Pass T, Harding GB, Wright R, Million C. Microbial and endotoxin contamination in water and dialysate in the central United States. Artif Organs 1990; 14:85-94. [PUBMED] |
|2.||Vanholder R, Vanhaecke E, Ringoir S. Waterborne Pseudomonas septicemia. ASAIO Trans 1990;36:M215-6. [PUBMED] |
|3.||Tokars JI, Alter MJ, Favero MS, Moyer LA, Bland LA. National surveillance of hemodialysis associated diseases in the United States, 1990. ASAIO J 1993;39:71-80. [PUBMED] |
|4.||Vanholder R, Vanhaecke E, Ringoir S. Pseudomonas septicemia due to deficient disinfectant mixing during reuse. Int J Artif Organs 1992;15:19-24. [PUBMED] |
|5.||Jackson BM, Beck-Sague CM, Bland LA, Arduino MJ, Meyer L, Jarvis WR. Outbreak of pyrogenic reactions and gramnegative bacteremia in a hemodialysis center. Am J Nephrol 1994;14:85-9. [PUBMED] |
|6.||Gordon SM, Oettinger CW, Bland LA, et al. Pyrogenic reactions in patients receiving conventional, high-efficiency, or high-flux hemodialysis treatments with bicarbonate dialysate containing high concentrations of bacteria and endotoxin. J Am Soc Nephrol 1992;2:1436-44. [PUBMED] |
|7.||Shaldon S, Dinarello CA. The relationship between biocompatibility and interleukin-1. Life Support Syst 1987;5:341-5. [PUBMED] |
|8.||Shaldon S, Koch KM. Biocompatibility in hemodialysis: clinical relevance in 1995. Artif Organs 1995;19:395-7. [PUBMED] |
|9.||Berland Y, Brunet P, Ragon A, Reynier JP. Dialysis fluid and water: their roles in biocompatibility. Nephrol Dial Transplant 1995;10(Suppl 10):45-7. [PUBMED] |
|10.||Lundberg L, Stegmayr BG, Wehle B. Backdiffusion or bicarbonate may stimulate complement activation during haemodialysis with low-flux membranes. Int J Artif Organs 1994;17:131-6. [PUBMED] |
|11.||Bland LA, Oliver JC, Arduino MJ, Oettinger CW, McAllister SK, Favero MS. Potency of endotoxin from bicarbonate dialysate compared with endotoxins from Escherichia coli and Shigella flexneri. J Am Soc Nephrol 1995;5:1634-7. [PUBMED] |
|12.||Arduino MJ, Bland LA, McAllister SK, Favero MS. The effects of endotoxincontaminated dialysate and polysulfone or cellulosic membranes on the release of TNF alpha during simulated dialysis. Artif Organs 1995;19:880-6. [PUBMED] |
|13.||Pereira BJ, Sundaram S, Barrett TW, et al. Transfer of cytokine-inducing bacterial products across hemodialyzer membranes in the presence of plasma or whole blood. Clin Nephrol 1996;46:394-401. [PUBMED] |
|14.||Schindler R, Krautzig S, Lufft V, et al. Induction of interleukin-1 and interleukin-1 receptor antagonist during contaminated in-vitro dialysis with whole blood. Nephrol Dial Transplant 1996;11:101-8. |
|15.||Perez-Garcia R, Anaya F, Chisvert J, Valderrabano F. Association of high-flux dialysers and bacterial contamination of dialysate-induced chronic release of cytokines in haemodialysis patients. Nephrol Dial Transplant 1995;10:2164-6. [PUBMED] [FULLTEXT]|
|16.||Lonnemann G. Chronic inflammation in hemodialysis: the role of contaminated dialysate. Blood Purif 2000;18:214-23. [PUBMED] [FULLTEXT]|
|17.||Panichi V, Migliori M, De Pietro S, et al. The link of biocompatibility to cytokine production. Kidney Int 2000;58(Suppl 76):S96-103. |
|18.||Mion CM, Canaud B, Garred LJ, Stec F, Nguyen QV. Sterile and pyrogen-free bicarbonate dialysate: a necessity for hemodialysis today. Adv Nephrol Necker Hosp 1990;19:275-314. [PUBMED] |
|19.||Krautzig S, Lonnemann G, Shaldon S, Koch KM. Bacterial challenge of NISSHO ultrafilter ETF 609: results of in vitro testing. Artif Organs 1996;20:798-800. [PUBMED] |
|20.||Lonnemann G, Schindler R. Ultrafiltration using the polysulfone membrane to reduce the cytokine-inducing activity of contaminated dialysate. Clin Nephrol 1994;42(Suppl 1):S37-43. [PUBMED] |
|21.||Cappelli G, Tetta C, Cornia F, et al. Removal of limulus reactivity and cytokine-inducing capacity from bicarbonate dialysis fluids by ultrafiltration. Nephrol Dial Transplant 1993;8:1133-9. [PUBMED] [FULLTEXT]|
|22.||Sterilizing filtration of liquids. Technical report no. 26. Parenteral Drug Association. PDA J Pharm Sci Technol 1998;52(Suppl 1):1-31. |
|23.||Canaud B, Bosc JY, Leray H, Morena M, Stec F. Microbiologic purity of dialysate: rationale and technical aspects. Blood Purif 2000;18:200-13. [PUBMED] [FULLTEXT]|
|24.||Port FK, VanDeKerkhove KM, Kunkel SL, Kluger MJ. The role of dialysate in the stimulation of interleukin-1 production during clinical hemodialysis. Am J Kidney Dis 1987;10:118-22. [PUBMED] |
|25.||Lonnemann G. Dialysate bacteriological quality and the permeability of dialyzer membranes to pyrogens. Kidney Int Suppl 1993;41:S195-200. [PUBMED] |
|26.||Lonnemann G. Should ultrapure dialysate be mandatory ? Nephrol Dial Transplant 2000;15 Suppl 1:55-9. [PUBMED] [FULLTEXT]|
|27.||Floege J, Ketteler M. beta2-Microglobulinderived amyloidosis: An update. Kidney Int 2001;59:S164-71. |
|28.||Schindler R, Lonnemann G, Schaffer J, Shaldon S, Koch KM, Krautzig S. The effect of ultrafiltered dialysate on the cellular content of interleukin-1 receptor antagonist in patients on chronic hemodialysis. Nephron 1994;68:229-33. |
|29.||Baz M, Durand C, Ragon A, et al. Using ultrapure water in hemodialysis delays carpal tunnel syndrome. Int J Artif Organs 1991;14:681-5. [PUBMED] |
|30.||Schwalbe S, Holzhauer M, Schaeffer J, Galanski M, Koch KM, Floege J. Beta 2microglobulin associated amyloidosis: a vanishing complication of long-term hemodialysis? Kidney Int 1997;52:1077-83. [PUBMED] |
|31.||Panichi V, Tetta C, Rindi P, Palla R, Lonnemann G. Plasma C-reactive protein is linked to backfiltration associated interleukin-6 production. ASAIO J 1998;44:M415-7. [PUBMED] |
|32.||Pegues DA, Oettinger CW, Bland LA, et al. A prospective study of pyrogenic reactions in hemodialysis patients using bicarbonate dialysis fluids filtered to remove bacteria and endotoxin. J Am Soc Nephrol 1992;3:1002-7. [PUBMED] |
|33.||Schiffl H, Lang SM, Bergner A. Ultrapure dialysate reduces dose of recombinant human erythropoietin. Nephron 1999;83: 278-9. [PUBMED] [FULLTEXT]|
|34.||Kaysen GA. Inflammation nutritional state and outcome in end stage renal disease. Miner Electrolyte Metab 1999;25:242-50. [PUBMED] |
|35.||Drueke TB. Beta2-microglobulin and amyloidosis. Nephrol Dial Transplant 2000;15(Suppl 1):17-24. |
|36.||Di Felice A, Cappelli G, Facchini F, et al. Ultrafiltration and endotoxin removal from dialysis fluids. Kidney Int Suppl 1993;41: S201-4. [PUBMED] |
|37.||Cappelli G, Perrone S, Ciuffreda A. Water quality for on-line hemodiafiltration. Nephrol Dial Transplant 1998;13(Suppl 5):12-6. [PUBMED] [FULLTEXT]|
|38.||Brunet P, Berland Y. Water quality and complications of haemodialysis. Nephrol Dial Transplant 2000;15:578-80. [PUBMED] [FULLTEXT]|
|39.||Lonnemann G. The quality of dialysate: an integrated approach. Kidney Int 2000; 58(Suppl 76):S112-9. |
|40.||Perez-Garcia R, Rodriguez-Benitez PO. Why and how to monitor bacterial contamination of dialysate ? Nephrol Dial Transplant 2000;15:760-4. |
|41.||Bambauer R, Walther J, Meyer S, et al. Bacteria- and endotoxin-free dialysis fluid for use in chronic hemodialysis. Artif Organs 1994;18:188-92. [PUBMED] |
|42.||Lonnemann G, Krautzig S, Koch KM. Quality of water and dialysate in haemodialysis. Nephrol Dial Transplant 1996;11:946-9. [PUBMED] [FULLTEXT]|
|43.||Ledebo I, Nystrand R. Defining the microbiological quality of dialysis fluid. Artif Organs 1999;23:37-43. [PUBMED] [FULLTEXT]|
|44.||AAMI. Standard/American National Standard. Water treatment equipment for hemodialyis applications. AAMI/ DS RD62 2000. |
|45.||ISO/CD. Water for hemodialysis and hemodiafiltration. ISO/CD 13959 and 13958. |
|46.||European Pharmacopoeia. Haemodialysis solutions, concentrated, water for diluting. European Pharmacopoeia 3 rd Ed 2000. |
|47.||Bambauer R, Schauer M, Jung WK, Daum V, Vienken J. Contamination of dialysis water and dialysate. A survey of 30 centers. ASAIO J 1994;40:1012-6. |
|48.||Harding GB, Klein E, Pass T, Wright R, Million C. Endotoxin and bacterial contamination of dialysis center water and dialysate; a cross sectional survey. Int J Artif Organs 1990;13:39-43. [PUBMED] |
|49.||Arvanitidou M, Spaia S, Katsinas C, et al. Microbiological quality of water and dialysate in all haemodialysis centres of Greece. Nephrol Dial Transplant 1998; 13:949-54. [PUBMED] [FULLTEXT]|
|50.||Vorbeck-Meister I, Sommer R, Vorbeck F, Horl WH. Quality of water used for hemodialysis: bacteriological and chemical parameters. Nephrol Dial Transplant 1999; 14:666-75. |
|51.||Laurence RA, Lapierre ST. Quality of hemodialysis water: a 7-year multicenter study. Am J Kidney Dis 1995;25:738-50. [PUBMED] |
|52.||Gault MH, Duffett AL, Murphy JF, Purchase LH. In search of sterile, endotoxin-free dialysate. A J 1992;38:M431-5. |
|53.||Takamiya T. Efforts to reduce the endotoxin levels in dialysate. Contrib Nephrol 1994;108:46-52. [PUBMED] |
|54.||Canaud BJ, Mion CM. Water treatment for contemporary hemodialysis. In: Jacobs C, Kjellstrand CM, Koch KM, Winchester JF, eds. Replacement of Renal Function by Dialysis. Dordrecht: Kluwer Academic Publishers 1996:231-255. |
|55.||Bambauer R, Walther J, Jung WK. Ultrafiltration of dialysis fluid to obtain a sterile solution during hemodialysis. Blood Purif 1990;8:309-17. [PUBMED] |
|56.||Oliver JC, Bland LA, Oettinger CW, et al. Bacteria and endotoxin removal from bicarbonate dialysis fluids for use in conventional, high-efficiency, and highflux hemodialysis. Artif Organs 1992; 16:141-5. [PUBMED] |
|57.||Frinak S, Polaschegg HD, Levin NW, Pohlod DJ, Dumler F, Saravolatz LD. Filtration of dialysate using an on-line dialysate filter. Int J Artif Organs 1991; 14:691-7. [PUBMED] |
|58.||Arduino MJ. Proper mechanisms for assuring disinfectant concentrations for use in hemodialysis. Nephrol News Issues 1999;13:18,23,27. [PUBMED] |
|59.||Ledebo I. On-line hemodiafiltration: technique and therapy. Adv Ren Replace Ther 1999;6:195-208. [PUBMED] |
|60.||Canaud B, Bosc JY, Leray H, Stec F. Microbiological purity of dialysate for online substitution fluid preparation. Nephrol Dial Transplant 2000;15(Suppl 2):21-30. |
|61.||Krautzig S, Linnenweber S, Schindler R, Shaldon S, Koch KM, Lonnemann G. New indicators to evaluate bacteriological quality of the dialysis fluid and the associated inflammatory response in ESRD patients. Nephrol Dial Transplant 1996; 11(Suppl 2):87-91. [PUBMED] |
|62.||Harding GB, Pass T, Wright R. Bacteriology of hemodialysis fluids: are current methodologies meaningful? Artif Organs 1992;16:448-56. [PUBMED] |
|63.||van der Linde K, Lim BT, Rondeel JM, Antonissen LP, de Jong GM. Improved bacteriological surveillance of hemodialysis fluids: a comparison between Tryptic soy agar and Reasoner's 2A media. Nephrol Dial Transplant 1999;14:2433-7. [PUBMED] [FULLTEXT]|
|64.||Harding GB, Pass T, Million C, Wright R, DeJarnette J, Klein E. Bacterial contamination of hemodialysis center water and dialysate: are current assays adequate? Artif Organs 1989;13:155-9. [PUBMED] |
|65.||Pass T, Wright R, Sharp B, Harding GB. Culture of dialysis fluids on nutrient-rich media for short periods at elevated temperatures underestimate microbial contamination. Blood Purif 1996;14:136-45. [PUBMED] |
|66.||Lonnemann G. Assessment of the quality of dialysate. Nephrol Dial Transplant 1998;13(Suppl 5):17-20. [PUBMED] [FULLTEXT]|
|67.||Pearson FC, Dubczak J, Weary M, Anderson J. Determination of endotoxin levels and their impact on interleukin-1 generation in continuous ambulatory peritoneal dialysis and hemodialysis. Blood Purif 1988;6:207-12. [PUBMED] |
|68.||Tsuchida K, Takemoto Y, Yamagami S, et al. Detection of peptidoglycan and endotoxin in dialysate, using silkworm larvae plasma and limulus amebocyte lysate methods. Nephron 1997;75:438-43. [PUBMED] |
|69.||Morin P. Identification of the bacteriological contamination of a water treatment line used for haemodialysis and its disinfection. J Hosp Infect 2000;45:218-24. [PUBMED] [FULLTEXT]|
|70.||Sundaram S, Auriemma M, Howard G Jr, Brandwein H, Leo F. Application of membrane filtration for removal of diminutive bioburden organisms in pharmaceutical products and processes. PDA J Pharm Sci Technol 1999;53:186-201. |
|71.||Arduino MJ, Bland LA, Aguero SM, Favero MS. Effects of incubation time and temperature on microbiologic sampling procedures for hemodialysis fluids. J Clin Microbiol 1991;29:1462-5. [PUBMED] [FULLTEXT]|
|72.||Panichi V, Migliori M, De Pietro S, Taccola D, Metelli MR, Palla R. Plasma Creactive protein in haemodialysis. Blood Purif 1999; 17:142-8. [PUBMED] [FULLTEXT]|
|73.||Panichi V, Migliori M, De Pietro S, et al. C-reactive protein as a marker of chronic inflammation in uremic patients. Blood Purif 2000;18:183-90. [PUBMED] [FULLTEXT]|
|74.||Roth VR, Jarvis WR. Outbreaks of infection and/or pyrogenic reactions in dialysis patients. Semin Dial 2000;13:92-6. [PUBMED] [FULLTEXT]|
|75.||Vincent FC, Tibi AR, Darbord JC. A bacterial biofilm in a hemodialysis system. Assessment of disinfection and crossing of endotoxin. ASAIO Trans 1989;35:310-3. |
|76.||Phillips G, Hudson S, Stewart WK. Persistence of microflora in biofilm within fluid pathways of contemporary hemodialysis monitors (Gambro AK-10). J Hosp Infect 1994;27:117-25. [PUBMED] [FULLTEXT]|
|77.||Man NK, Degremont A, Darbord JC, Collet M, Vaillant P. Evidence of bacterial biofilm in tubing from hydraulic pathway of hemodialysis system. Artif Organs 1998;22:596-600. [PUBMED] [FULLTEXT]|
|78.||Cappelli G, Ballestri M, Perrone S, Ciuffreda A, Inguaggiato P, Albertazzi A. Biofilms invade nephrology: effects in hemodialysis. Blood Purif 2000;18:224-30. [PUBMED] [FULLTEXT]|
Department of Nephrology, Lapeyronie University Hospital, CHU Montpellier, 371, Ave. du Doyen G. Giraud, 34295 Montpellier
[Table - 1], [Table - 2]
| Article Access Statistics|
| Viewed||6547 |
| Printed||127 |
| Emailed||0 |
| PDF Downloaded||603 |
| Comments ||[Add] |