In Europe, patients receiving hemodialysis undergo at least three treatment sessions a week. As standard hemodialysis treatment sessions last 4–6 hours, individual patients are exposed to 15,000–20,000 L of dialysis fluid yearly. In hemodiafiltration procedures, dialysis water is administered in the form of dialysate and infusate up to 3,400–6,800 L directly following the ultrafiltration through two or three dialysis water monitor ultrafilters [1
]. The increasing tendency to use on-line hemodialysis procedures implies therefore the potential presence in distribution rings of microbial, fungal, and chemical substances which should be carefully monitored, as provided for in specific guidelines [2
]. Moreover, waters should be tested by certified laboratories using significantly different analytical procedures, particularly in the case of microbiological controls, to those applied to test human blood and secretions [3
]. Numerous undesirable substances originate from polluted water or infiltrations in the drinking water supply network. Humans are the major culprits, contaminating waterworks through the use of ineffective measures to reduce bacterial and/or chemical pollutant loads originating from surface waters collected in artificial basins, or from the building of drinking water networks using obsolete or inappropriate materials. The majority of toxic contaminants derive from procedures applied in the treatment of municipal waters, thereby suggesting that these are not always safe for direct use in hemodialysis applications. An unmonitored dialysis water treatment facility, an inefficient system for the distribution of dialysis waters to monitors, or a scarce regularity in disinfection constitute the most frequent causes of harmful or fatal substances which may prove to be particularly hazardous when adopting on-line procedures lacking effective ultrafilters with administration. Thus, the main parameters to be applied in the treatment of waters destined for use in hemodialysis procedures, should be underlined.
As a premise enhancing evaluation of the evolution of the plants implemented, a synthesis of the most recent ANSI/AAMI/ISO guidelines published in 2009 and 2011 is provided [2
]. The Authors wish to underline that dialysis procedures used in the USA do not foresee the administration to patients of such a high number of infusions as occurs in Europe, when the nephrologist prescribes high convective methods such as hemodiafiltration. Furthermore, two-stage reverse osmosis (TRO) with overnight thermal disinfection is referred to, although not described in detail, in the AAMI Guidelines, and is to date applied scarcely throughout Italy and Europe.
Water utilized in hemodialysis applications is prepared in a series of different purification processes, the most common of which include [3
]: reverse osmosis, deionization, and carbon filtration. Reverse osmosis (RO) uses high pressure to force water across a semi-permeable membrane to form product water (permeate), thereby rejecting 90 to 99 percent of ionic contaminants and >95 percent of non-ionic contaminants. A RO membrane is an effective barrier against microbiological contaminants, bacteria, viruses, and endotoxins. Currently however, two-stage reverse osmosis is actually the most effective form compared to one-stage reverse osmosis (SRO), achieving the highest degree of contaminant removal. This procedure is particularly recommended for use in on-line hemodialytic methods with high convective component [9
]. Deionization (DI) uses ion exchange resins to remove ionic contaminants from water by exchanging hydrogen ions for cationic resins and hydroxyl ions for anionic resins. Mixed bed deionizers contain both cationic and anionic resins but do not remove microbiological contaminants. Deionizer performance should be closely monitored to avoid exhaustion, and it should be taken into account that ions bind to the resin with low affinity. This phenomenon, which may lead to high contaminant concentrations in the product water as the deionizer becomes exhausted [10
], has been reported to cause acute, fatal fluoride toxicity in hemodialysis patients [11
]. This method is virtually obsolete in Italy. In the pre-treatment procedures a variety of filters may be utilized, both as pre-treatment for main tap water purification processes and at the end of the pre-treatment system to remove coarse particulate matter prior to purification and to protect RO membranes from fine particles washed out of carbon beds. The use of chlorination and dechlorination is not mandatory, although in a few circumstances (e.g., during the drought in Sardinia in 1991) municipal authorities have implemented provisions including water supply on alternate days, and consequent reduced pressure throughout the water supply networks, which were frequently old and leaking (personal observation); this resulted in an infiltration of polluted waters from the water table in the vicinity of tubes conveying the drinking water supply. It should moreover be underlined that in Italy the use of underground water tables in supplying water to hospitals is permitted. Good quality proportional pumps should be applied to guarantee optimal chorine concentration (0.5–1 ppm), although complete water dechlorination should be ensured upstream of osmosis membranes. To prevent inadvertent exposure of patients to chloramine as the capacity of the carbon is exhausted two carbon filters in series are necessary. Inadequate chloramine removal may occur however, and assays aimed at detecting the presence of chloramines with specific rapid water checks are mandatory [12
In water softeners resin beads inside the tanks display a high affinity for bivalent cations (calcium and magnesium) present in the feed water, releasing two sodium ions (monovalent) for each calcium or magnesium ion captured to prevent RO membranes from fouling by calcium and magnesium salts. Softeners must be regenerated by exposing resin to strong brine with a very high sodium concentration. Dechlorinators and softeners represent a suitable “pabulum” for bacterial growth due to the impossibility of disinfecting the same with a specific product unless thorough rinsing is undertaken against the flow. The treated water exits the central water treatment plant and is distributed to hemodialysis monitor by piping ring with an optimal diameter to avoid sluggish segments; metals such as brass, aluminium, or galvanized metal should not be used, and the distribution system must be designed as a closed ring. The use of polyvinyl chloride (PVC) should be eliminated and materials such as high corrosion resistance stainless steel (INOX AISI 316L) polyethylene thermoplastic polymer (PEX), and polyvinylidenefluoride (PVDF) used to construct piping and recently the polytetrafluoroethylene (PTFE) has been introduced.
The pollutant potential of reservoir storage is frequently underestimated. Tanks should be opaque, made of plastic for foodstuffs, and not be located in a “stagnant” corner of the circuit, but should guarantee a constant flow of water. However, a fundamental aspect is constituted by the bacteriological and endotoxin controls to be implemented in line with appropriate procedures in sampling and transportation, in inoculation of the culture medium with dialysis water, and in the accurate interpretation of results, not taking into account merely mesophiles from the environment, but furthering observation to evaluate the presence of bacteria or mycetes [13
]. Based on these premises therefore, a study was undertaken to assess the quality of water in five dialysis units in which over 16 years numerous changes had been implemented in methods used for disinfection and monitoring and improvements made to the equipment used in the production and distribution of ultrapure dialysis water, particularly in dialysis units adopting online convective procedures with production of high volumes of infusate, such as online hemodiafiltration techniques.
The Authors’ experience in five territorial dialysis units, implemented on the basis of microbiological results obtained at several points throughout the central plant and piping ring, have led to an improvement in microbiological/endotoxinic quality of water subsequent to changes made in the use of materials and procedures. Specifically, it has been demonstrated how, in the presence of materials other than PVC, regular disinfection and frequent controls (even monthly) represented a fundamental step forward in achieving low levels of CFU [23
]. The use of PVC should be avoided; it is not suited for use with thermal disinfection methods and evidence has indicated it’s potentially cancerogenic status [24
]. The overnight thermal disinfection achieved by means of biosmosis resulted in a dramatic decrease in microbial load [7
], which appeared to be more significant following the use of PEX compared to INOX in construction of the distribution ring. In the Authors’ opinion, this difference may be associated to diameter of piping; a minor diameter decreased the possibility of stagnant areas creating a less suitable habitat for biofilm growth. In fact it is fundamental that pressure along the walls, and velocity and intensity of fluid shear stress on the smaller inner surfaces, are higher than those recorded in larger-sized sections; in other words a higher water pressure and velocity enhance filling of the circuit and ensure against the formation of concealed areas where bacteria and hyphae may flourish. Moreover, frequent thermal disinfection does not rapidly prevent the formation of bacterial biofilm and hyphae along inner surfaces. Therefore, in the wake of experience gained in units operating with PVC rings, the Authors opted to abandon use of this material entirely. The application of meticulously implemented periodic thermal and chemical disinfection procedures should be further supported by additional checks and immediate correction of any “pathological” areas detected by microbiological results. Accordingly, a specialized team should be appointed to carry out controls and periodic and non-scheduled maintenance based on the finding of microbiological levels exceeding established safety limits.
Irrespective of the material used in construction of the distribution ring, the connection valves to dialysis monitors should be of stainless steel AISI 316L, in view of the potential liability of the connection and the increased risk of stagnant areas at this level: this option results in a decreased probability of microbial adhesions. In all the processes described, chemical, physical and bacteriological tests should be undertaken by a certified laboratory. The Authors maintain that standard procedures should be established in conjunction with an institution specializing in environmental water testing; labs should moreover possess a working knowledge of the equipment used and ensure that methods described in the leading guidelines in the field adhered to. A synergic action between the dialysis unit staff, the maintenance team and the lab is mandatory, with purpose-trained specialised technicians performing sampling throughout all units and providing for a correct transportation to the testing lab.
The Authors underlined how systems should be monitored continuously and the following taken into account [25
]: (a) on opting for the sole chemical disinfection, apply every 15–30 days solutions capable of removing both bacterial biofilms and potential mineral scales that may protect bacteria and/or enhance their survival; (b) daily nocturnal thermal disinfection; to promote safety, an additional monthly or twice monthly disinfection of osmosis membranes and ring as described in item.
The experience gained has led the Authors to progressively undertake alterations aimed at optimizing the microbiological quality of dialysis water: weak points may be represented by an excessive inner diameter of piping, both in PVC and INOX, resulting in pipes that are disproportionate to water flow and volume; the definitive abolishing of PVC and mesh tubes connecting the ring to monitors is fundamental.
Conversely, the strong points that emerged from the present study focused largely on the use of PEX. However, very few literature reports published to date have focused on the efficacy of the latter material in preventing the adhesion of bacterial biofilms. Stainless steel INOX AISI 316 L is a long-lasting but rather costly material; the length of duration however may promote the amortization of costs. On opting to use stainless steel assembly and soldering should be undertaken by specialized technicians in order to warrant a perfect connection between the various segments. The studies undertaken with stainless steel were perfectly satisfactory; however, the Authors prefer to underline the suitability of PEX circuits which have no seams and, according to the quality of water, provide for a scheduled replacement of the circuit every 7–10 years. The importance of applying a correctly-sized piping and an antireflux gooseneck drainage spout should be underlined.
The carrying out of a regular and scrupulous microbiological surveillance enables physicians and microbiologists to identify the faulty part of equipment and/or ring piping and implement the required improvements to materials, equipment, and disinfection procedures. Indeed, this result was achieved in the territorial dialysis centres investigated in the present study, all of which featured significantly diverse hydrological and geographic differences.
Over a 16-year period the dynamic procedures set up have demonstrated how TRO should be considered a necessary investment to be faced with the aim of establishing a safer microbiological profile and producing a positive impact on microinflammation in dialysis patients, particularly in the case of increased infusion volumes during on-line hemodiafiltration procedures [26
]. Likewise, daily overnight thermal disinfection procedures have proved at times to be more effective than frequent chemical disinfection.
Finally, it has become increasingly clear how staff operating in nephrology and microbiology units should possess a strong, motivated cultural synergic background on this complex subject in order to supply the best possible quality water to consumers. Indeed, dialysis water today should be considered a “medicinal product” in its own right.