Monitoring the microbial purity of the treated water and dialysate.

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.

Microbiological purity of dialysate for on-line substitution fluid preparation.

Dialysate purity has become a major concern in recent years since it was shown that low levels of endotoxin in dialysate were able to induce the production of proinflammatory cytokines, which were putatively implicated in the development of dialysis-related pathology. On-line haemodiafiltration (HDF; or haemofiltration) using the dialysate as the source of substitution fluid magnifies this risk and reinforces the critical role of the dialysate quality to be used. In order to virtually abolish the risk related to dialysate contaminants, it is mandatory to ensure the highest purity of the dialysate used in order that the substitution fluid produced satisfies the quality demands of a sterile and pyrogen-free infusion solution. Ultrapure dialysate production is therefore a common need for all on-line systems where substitution fluid is prepared continuously by sterilizing filtration of the dialysate. However, since dialysate purity plays a role in the complex haemocompatibility interaction which occurs during the haemodialysis session, the use of ultrapure dialysate must be considered as a suitable option for all haemodialysis modalities. To achieve this goal, one must keep in mind that ultrapure dialysate and infusate result from a complex chain of production where ultrapurity and/or sterility of the final solution relies on the weakest or worst component of the chain. Reliable production of ultrapure dialysate and infusate relies on several prerequisites: use of ultrapure water, use of clean electrolytic concentrates, implementation of ultrafilters on specifically designed HDF machines, microbiological monitoring of the chain with adequate and sensitive methods, and hygienic handling of the chain including frequent disinfection to reduce the level of contamination and to prevent biofilm formation. When properly done, the safety and reliability of on-line systems have been confirmed in large clinical studies. It is now time to validate the on-line process in large controlled clinical trials.

Microbiologic purity of dialysate: rationale and technical aspects.

Dialysate purity has become a major concern in hemodialysis since it has been shown that microbial-derived products were stimulating the production and the release of proinflammatory cytokines in hemodialysis patients. This chronic microinflammatory state induced by hemodialysis has been putatively implicated in the development of dialysis-related pathology. In order to prevent risk related to these offenders and to reduce patient/dialysis interaction, it appears highly desirable to use ultrapure dialysis fluid aiming at sterility and apyrogenicity on a regular basis. Ultrapure dialysate results from a complex chain of production where purity grade relies on the weaker link of this chain. Technical aspects and pitfalls in the production of ultrapure dialysate are summarized in this paper. Production of ultrapure dialysate may be achieved on a routine basis, provided adequate components are used, and hygienic handling is regularly ensured. It includes the use of ultrapure water, clean and or sterile electrolytic concentrates (liquid or powder), implementation of ultrafilters on hemodialysis machines, microbiologic monitoring and hygienic handling of the chain with frequent disinfection. Safety and reliability of ultrapure dialysate production relies on a continuous quality assurance process, where results are coupled to corrective action in a feedback loop process.

On-line haemodiafiltration: state of the art.

Faced with the shortcomings of conventional dialysis on a long-term basis, as illustrated by the dialysis-related pathology, a need for a new strategy exists to improve the overall quality of treatment in end-stage renal failure (ESRF) patients. On-line haemodiafiltration (HDF) seems to be the best therapeutic option to achieve this goal at the present time. By enhancing convective clearances through highly permeable membranes, HDF offers the greatest solute fluxes both for low and higher molecular weight uraemic toxins. As for example, in our routinely performed HDF programme based on 3 weekly sessions lasting 3-4 h each, double-pool urea Kt/V achieved was 1.55+/-0.20 and beta2-microglobulin Kt/V was 0.91. By producing substitution fluid from fresh dialysate, the technique of HDF is simplified and becomes economically affordable. By improving the haemodynamic tolerance, HDF allows more elderly and high risk cardiovascular patients to be treated more safely. By using bicarbonate-buffered infusate, HDF facilitates the correction of acidosis. Both by using ultrapure bicarbonate dialysate and down-regulating the membrane reactivity via a 'protein cake', HDF introduces the first step for a full haemocompatibility concept. Finally, by giving access to virtually unlimited amounts of sterile and non-pyrogenic fluid, HDF should introduce new therapeutic options such as a totally automated and feed-back-controlled machine. Today's on-line HDF is already a step forward to enhance the overall efficacy of renal replacement therapy and to improve the global care of ESRF patients.

Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement.

The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.

[Hemodiafiltration with on-line production of bicarbonate infusate: 5 years of clinical experience]. / Hémodiafiltration (HDF) avec production "en ligne" d'infusat au bicarbonate: 5 ans d'expérience clinique.

Despite its potential advantages HDF has not gained large clinical acceptance among nephrologist due to its technical complexity and to the large quantity of pharmaceutical substitution fluid needed. HDF with on-line production of substitution fluid from dialysate simplifies the procedure and reduces the cost of treatment session. We treated regularly 13 high risk and/or non-compliant patients (9 males, 4 females) with HDF for 46 +/- 17 months. HDF program consisted of 3 sessions weekly lasting 210 +/- 10 mn with blood flow rate 350 +/- 20 ml/mn and fluid volume exchange of 20 liters/session. High flux dialyzers (HF80, Filtral 16) were reused 6 to 13 times automatically on a Renatron machine with peroxyacetic acid solution as sole cleaning and disinfecting agent. Microbiologic quality of infusate was assessed by membrane filtration culturing method and LAL endotoxin determination. 3937 HDF sessions were performed. 57.140 I of substitution fluid were infused IV to patients. Eight pyrogenic reactions were observed: 2 due to septicemia related to catheter infection and 6 from unknown origin. Adequacy of program was achieved in all patients. Blood pressure control was satisfactorily obtained without antihypertensive medication in 12/13 patients. Effective weekly integrated urea clearances was 150 +/- 15 l/wk, KT/V index was 1.50 +/- 0.10, urea TAC 20 +/- 2 mM/l and protein catabolic rate 1.40 +/- 0.10 g/kg/24 h. We conclude that HDF with on-line production of bicarbonate substitution fluid is a safe and highly efficient method cost-competitive with bicarbonate HD, which offers an interesting alternative for renal replacement therapy.

Clinical and microbiological evaluation of a postdilutional hemofiltration system with in-line production of substitution fluid.

Safety and efficacy of a recently developed hemofiltration (HF) system with in-line production of substitution fluid (GHS-10; Gambro, Lund, Sweden) based on a sterilizing filtration of acetate buffered dialysate has been evaluated in 4 patients over a 6-month period. Two patients were prematurely excluded from the study: 1 because of acetate intolerance and the other because of kidney transplantation. Two patients completed the study (240 HF sessions). Treatment adequacy was maintained in the 2 medium term treated patients according to the usual clinical and biochemical criteria and a mean exchange volume of 100-105 liters/week (30-35 liters/session three times weekly). Urea kinetic modeling analysis performed over all HF cycles gave the following results: dialysis index (urea clearance.time-on HF/urea volume space) (KT/V) approximately 1-1.1, urea time averaged concentration (UREA TAC) approximately 15-20 mmol/l, and protein catabolic rate (PCR) approximately 1.1-1.2 g/kg/day. Rare clinical adverse symptoms observed during the course of sessions were attributed to acetate intolerance. Microbiological safety was confirmed in vivo by the absence of pyrogenic reactions after 240 HF sessions (approximately 7 m3 substitution fluid infused intravenously) and in vitro by the constant absence of bacteria and/or endotoxin content limulus amaebocyte lysate (LAL) sensibility threshold 10 pg/l within the infusate produced during the sham HF sessions. The fluid mass balance obtained with the GHS-10 monitor was excellent. The electrolyte composition as judged by Na variation remained in a range of 2-3%. GHS-10 used in this study for postdilutional HF confirms that a large quantity of intravenous quality fluid may be safely produced by ultrafiltration from dialysate. It also introduced a new dimension in biocompatibility of dialysis by demonstrating that sterile dialysate may be routinely produced and used for routine dialysis.

Standard methods for the microbiological assessment of electrolyte solution prepared on line for haemofiltration.

The preparation of large volumes of intravenous solution at the bedside (on-line preparation) requires bacteriological monitoring and pyrogen control before final sterilisation. We tested the sensitivity of microbiological methods and their applicability in routine clinical conditions during haemofiltration. In vitro, the 0.22 micron membrane filter technique (MF) showed a better or equal bacterial recovery with two test organisms. Parallel tests of 0.22 and 0.45 micron MF under simulated haemofiltration conditions showed no significant difference in the number of detected bacteria. Routine MF with 0.22 micron membranes offers a simple and reliable way to monitor the bacterial content of on-line prepared electrolyte solution in clinical conditions.