Reuse of dialyzers

INTRODUCTION — Hemodialyzer reuse refers to the practice of using the dialyzer multiple times for a single patient. Dialyzer reuse appears to be a safe and cost-effective procedure for high-flux and high-urea removal dialyzers.

Reuse was commonly practiced in the United States during the 1980s through 1990s, largely for cost containment but also to reduce the incidence of inflammatory reactions due to blood-membrane interactions with bioincompatible cellulosic membranes [1-3]. The practice has markedly decreased since that time in the United States, largely due to the risk of bacterial bloodstream infections from reuse of dialyzers [3-5]. In 2005, approximately 40 percent of dialysis units in the United States were thought to reuse dialyzers [2,3]. As of 2020, the three largest dialysis organizations in the United States do not perform reuse in any of their facilities. However, as recently as 2017, there was a report of an adverse consequence of reuse (bacterial bloodstream infections) in the United States [4,5]. Dialyzer reuse is now rare in the United States and most resource-rich countries. Reuse is still performed in other parts of the world, particularly in countries with limited resources to dedicate to kidney replacement therapies [6-11].

Only hollow-fiber dialyzers that are labeled by the manufacturer for multiple use are reprocessed [12]. The methods used to ensure optimal performance of the reused dialyzer are best suited to hollow-fiber dialyzers. (See 'Performance testing' below.)

This topic reviews methods of reprocessing hemodialyzers for reuse. Standards for hemodialysis, including water processing, are discussed elsewhere. (See "Assuring water quality for hemodialysis" and "Contaminants in water used for hemodialysis".)

REPROCESSING TECHNIQUES — The basic procedure for dialyzer reprocessing involves four steps: rinsing, cleaning, performance testing, and disinfection and sterilization. Dialyzer processing may be performed manually or with the use of automated equipment. Most reprocessing in the United States is done using automated methods, which may be more reliable and predictable, though few good studies have compared methods. One study showed no significant difference in mortality between processing techniques when identical germicides were used [13]. (See 'Clinical outcomes with reuse' below.)

A variety of guidelines have emerged to ensure safety and effectiveness of the reprocessing procedure. The Association for the Advancement of Medical Instrumentation (AAMI) has published recommendations for dialyzer reprocessing techniques [14,15].

In the United States, the Center for Medicare and Medicaid Services (CMS) requires all dialysis centers that reprocess dialyzers to comply with the AAMI guidelines as a condition for reimbursement [16]. Additional regulations may be imposed by city, county, or state health departments.

Individual reprocessing steps are discussed below.

Rinsing — At the termination of dialysis, the dialyzer is rinsed and filled with saline while still at the dialysis machine. The dialyzer is then reprocessed within two hours or refrigerated if reprocessing is delayed (usually only for 36 to 48 hours) [17]. At the time of reprocessing, the dialyzer is flushed with pressurized dialysis-quality water (ie, AAMI-standard water). Removal of residual blood may be enhanced by reverse ultrafiltration. Some centers use hydrogen peroxide in the rinsing procedure.

Cleaning — Cleaning agents include peracetic acid-based products (such as Renalin [which is a combination of 4.5 percent peracetic acid and 28 percent hydrogen peroxide (PAM)]) and sodium hypochlorite (ie, bleach [≤0.06 percent]). Renalin is more commonly used.

Bleach may damage the membrane and increase the ultrafiltration coefficient (ie, water permeability) [18]. In addition, bleach processing removes protein deposits that confer biocompatibility to bioincompatible membranes and causes certain dialyzers (polysulfone) to leak protein, the amount of which increases with the number of reuses [19]. It is not known whether other types of dialyzers are as sensitive to the adverse effects of bleach processing. Some manufacturers of polysulfone dialyzers have developed membranes that are less sensitive to these effects.

Performance testing — The performance of the dialyzer should be closely monitored. Performance testing includes tests of membrane integrity, clearance, and ultrafiltration capability.

●Membrane integrity – A blood path integrity test checks for leaks in the dialyzer casing, membrane, and supporting materials. Pressurized air, nitrogen, or reverse osmosis water is pumped into the blood side, or negative pressure is applied to the dialysate side of the membrane to generate a pressure gradient across the membrane. A drop in the pressure gradient indicates membrane leakage.

●Clearance – The fiber bundle volume (FBV) provides an indirect estimate of the change in dialyzer clearance. The FBV is the total fluid volume contained on the blood side of the membrane and tends to decrease with increasing number of reuses. The FBV is measured by filling the blood compartment of the dialyzer with fluid and then forcing air or nitrogen into the blood compartment and measuring the volume or weight of expelled fluid. The baseline FBV should be determined before the dialyzer is used for the first time; subsequent FBV measurements are compared with the baseline value. A decrease in FBV of 20 percent of the original value generally correlates to a 10 percent decrease in urea clearance [20,21]. However, studies that demonstrated this correlation were performed with cellulosic dialyzers, and no such work has been corroborated with modern dialyzers.

We agree with the 2006 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines that reused dialyzers should have either blood compartment volume at least 80 percent of original measured volume or urea clearance at least 90 percent of original measured clearance [22].

The FBV measured with in vitro methods (on the reprocessing machine when the dialyzer is disconnected from the patient) may differ from the FBV present during actual dialysis due principally to flushing of clot out of the fibers, which occurred prior to disconnection from the patient [23].

●Ultrafiltration capability – The ultrafiltration capability (ie, in vitro ultrafiltration coefficient) of the dialyzer is determined by measuring the volume of water that passes through the membrane at a given temperature and pressure.

Disinfection and sterilization — Methods of disinfection may be chemical (ie, peracetic acid, formaldehyde, or glutaraldehyde) or heat based. In a survey of dialysis units performed in 2002, the following were the percentage of centers using the various methods for reprocessing [24]:

●Peracetic acid product (such as Renalin; 72 percent)

●Formaldehyde (20 percent)

●Glutaraldehyde (4 percent)

●Heat (4 percent)

Chemical disinfection — Germicides are instilled into the blood and dialysate compartments before final inspection and storage. As noted above, the most commonly used germicide is a peracetic acid product, but 4 percent formaldehyde or 0.8 percent glutaraldehyde (a derivative of formaldehyde) can also be used.

The Centers for Disease Control and Prevention (CDC) have recommended the use of 4 percent formaldehyde for at least 48 hours during reprocessing [25]. The use of lower percentages of formaldehyde may allow the growth of organisms. (See 'Infection risk' below.)

Germicides must be completely removed by flushing of both blood and dialysate compartments before the dialyzer is used.

Adverse reactions to chemical disinfectants are rare if meticulous techniques are followed. (See 'Germicide exposure' below.)

Heat disinfection — Studies have suggested that heat disinfection is a safe and effective reprocessing technique, at least with specific dialyzers (eg, Fresenius polysulfone dialyzers) [26].

Heat disinfection involves filling the dialyzer with dialysis-quality water after cleaning and placing the dialyzer in a 105°C convection oven for 20 hours [27].

Another alternative method is to use a lower concentration of formaldehyde (0.7 to 1 percent) in combination with heating to between 95° and 110°C.

The heat disinfection process has also been modified by the addition of 1.5 percent citric acid [27]. This change has allowed lower temperatures to be used (95°C), thereby reducing thermal stress on the dialyzer and avoiding the use of germicides.

Heat disinfection can only be used for polysulfone dialyzers.

An advantage of heat processing is that it eliminates staff and patient exposure to germicides. There are two disadvantages to heat disinfection. Heat disinfection is not available in an automated form. In addition, the number of reuses with heat disinfection may be less than with chemicals due primarily to deterioration of the casing.

Inspection, labeling, and storage — The dialyzer should be carefully inspected at the end of the reprocessing procedure and when the reprocessed dialyzer is being set up for the next dialysis treatment. The dialyzer is carefully relabeled with the patient's name (with appropriate warnings about similar names in the unit), manufacturer label, the number of reuses, the baseline and current FBV, the time and date of reprocessing, and whether the dialyzer passed performance testing. The dialyzer is stored in a temperature-controlled storage room. The maximum allowable storage time depends upon the germicide used. Peracetic acid-processed dialyzers should be stored for a maximum of 14 days [12].

POTENTIAL RISKS — There are three major concerns with reuse: the risk of infection to patients or staff, loss of performance with impairment in clearance and/or ultrafiltration, and exposure of patients or staff to germicide.

Infection risk — Among all patients, care must be taken in the proper labeling of individual dialyzers to make certain that cross usage does not occur. There is no evidence that dialyzer reuse is associated with viral hepatitis or human immunodeficiency virus (HIV) transmission to patients or dialysis personnel if appropriate guidelines are followed. There are no recommendations against dialyzer reuse in hepatitis C- or HIV-infected patients. However, many clinicians absolutely oppose reuse in any patient known to be infected with these organisms.

To minimize any risk, dialyzers should be handled with universal precautions, and dialyzers from hepatitis B surface antigen-positive patients should be reprocessed and stored in a separate area.

Dialyzers from patients with sepsis or acute hepatitis should not be reused.

The risk of other nonviral infections also appears to be low if proper techniques are followed.

In the past, pyrogenic and mycobacterial infection had been related to subtherapeutic levels of peracetic acid and formaldehyde [25,28]. Pyrogenic reactions occur when endotoxins enter the bloodstream.

In 1985, it was reported that mycobacteria resistant to 2 percent formaldehyde were isolated from as many as 83 percent of dialysis unit water samples [25], and deaths in two dialysis units were attributed to dialysis-acquired Mycobacterium chelonae infection [28]. These outbreaks provoked changes in the recommended concentrations of germicide [25,28]. (See 'Disinfection and sterilization' above.)

More recent comparative and double-blind, randomized clinical trials have shown no increase in the risk of pyrogenic reactions with dialyzer reuse [29-32].

Usually, the cause of pyrogenic reactions is a contaminated water supply rather than a reused dialyzer. However, contaminated water used in the reprocessing of a dialyzer can contaminate the dialyzer even in the presence of germicides because bacteria can be trapped in areas where the germicide cannot penetrate. Pressures generated during dialysis can open the trapped areas, releasing viable bacteria. There may be a greater risk of infection in centers in which the dialyzer headers are removed during reprocessing. Issues concerning water purification are discussed separately. (See "Assuring water quality for hemodialysis".)

Loss of performance — Dialyzer performance decreases with increasing number of reuses. In one report, the measured Kt/V (ie, dialyzer clearance for urea) was significantly lower in dialyzers that had been reused many times (mean 14^th reuse) compared with dialyzers that had only been reused a few times (mean fourth reuse) [33]. Why this occurs is unclear but could relate to the progressive intradialytic loss of fiber bundle volume (FBV) and effective surface area that is not detected during postdialysis FBV measurements that are made on the reprocessing machine [23]. (See 'Performance testing' above.)

The type of cleaning agents used for reprocessing and the membrane type affect dialyzer performance.

Water permeability (ultrafiltration) may fall slightly after disinfection and reuse with peracetic acid products [34-36] and increase after reuse with bleach and formaldehyde [31,37,38].

The loss of water permeability results in a decrease in the convective clearance of middle-molecular-weight molecules, such as beta2-microglobulin. In the Hemodialysis (HEMO) study, the combination of bleach, formaldehyde, and an F80B dialyzer (a high-flux polysulfone membrane) increased the clearance of beta2-microglobulin, while reprocessing the same dialyzer with bleach and peracetic acid only modestly enhanced clearance [36]. Bleach reprocessing can increase inulin and myoglobulin clearance of F80B dialyzers and increase myoglobulin clearance of CT190 dialyzers [38]. There are negligible effects on urea, creatinine, and phosphorus removal with cellulose membranes [31].

Dialyzer clotting tends to increase with reuse and contributes to the decline in dialyzer performance. The heparin dose may need to be increased with reused dialyzers, although the heparin prescription is generally not adjusted automatically but rather on indication (ie, in the setting of clotting) [39]. (See "Anticoagulation for the hemodialysis procedure".)

Germicide exposure — Germicide exposure may cause adverse effects among patients and staff, and care must be taken in their removal. In addition, formaldehyde spills have occurred, temporarily disrupting dialysis routines.

●Staff – Some dialysis staff have developed allergic reactions to formaldehyde, which precludes their participation in reuse. Adverse reactions to chemical disinfectants are rare, however, if meticulous technique is followed [40].

●Patients – Among patients, the chronic exposure to formaldehyde has been associated with formation of antibodies to the erythrocyte N-antigen [41,42]. The anti-N-like antibodies are first seen 12 to 18 months after first exposure but eventually disappear if the modality of treatment is changed.

These antibodies have been associated with hemolysis and early transplant failure in some cases [20]. Thus, a test for removal of germicide is routinely performed prior to reuse of the dialyzer.

An anaphylactoid reaction has been reported in patients treated with reprocessed dialyzers sterilized with peracetic acid; these reactions appeared to be more frequent in patients taking angiotensin-converting enzyme (ACE) inhibitors [43]. Cessation of reuse led to resolution of symptoms despite continuation of the ACE inhibitor. The mechanism underlying these reactions is not known. One hypothesis is that some patients may have an interaction between a reused dialyzer and ACE inhibition. The latter may act by increasing kinin levels. ACE is also a kininase; as a result, ACE inhibition also inhibits kinin degradation. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Angioedema and anaphylactoid reactions' and "Reactions to the hemodialysis membrane".)

POTENTIAL BENEFITS — The major reason to reuse dialyzers is cost containment. However, reuse may have a beneficial effect on the biocompatibility of some dialyzers. The use of nonbiocompatible (cellulose-based) membranes is associated with complement activation, leukopenia, leukocyte sequestration with subsequent cytokine release, and dyspnea [44-46]. This cascade may play a role in dialysis-induced hypoxemia [46]. (See "Reactions to the hemodialysis membrane".)

Cuprophane dialyzers can be rendered biocompatible by reuse, possibly due to membrane coating by serum proteins [47]. In one study, cuprophane dialyzers were more biocompatible after reuse, as shown by improvement in the patient's peak expiratory flow rate when compared with new cuprophane dialyzers [48]. Removal of the protein coat with bleach, however, restores the membrane to its previous complement-activating state. There is no biological advantage from reusing biocompatible synthetic membranes since these membranes are associated with little or no complement activation.

Some have argued that reuse decreases the risk of the "first-use" syndrome. The first-use syndrome is an anaphylactoid immunoglobulin E (IgE)-mediated reaction that occurs during the first use of a dialyzer and is most often due to sensitization to ethylene oxide used for sterilization during manufacture of the dialyzer [49]. Reprocessing a new dialyzer thoroughly removes ethylene oxide. However, the incidence of the first-use syndrome is extremely low and can be reduced significantly without reprocessing by thorough rinsing of the dialyzer and blood lines before use. (See "Reactions to the hemodialysis membrane", section on 'Type A reactions'.)

The oxidative response of polymorphonuclear cells may be influenced by the type of dialyzer reuse. This was shown in an analysis from the Hemodialysis (HEMO) study in which the use of bleach or a peracetic acid-based product (Renalin) as a cleansing agent resulted in higher neutrophil superoxide bursts compared with that observed with aldehydes [50]. The clinical implication of these observations is unclear.

CLINICAL OUTCOMES WITH REUSE — There are no good data that show that reuse affects mortality. Many observational studies have been performed with variable results [13,29,51-62]. Increase, decrease, and no change in mortality have been reported, with variation due in part to differences in study techniques and periods of study [51]. A meta-analysis that included 14 studies (n = 956,807 patients) found no difference in mortality between patients undergoing multiple-use versus single-use dialysis [7]. However, most studies were deemed to be of poor quality. In addition, early studies may not be generalizable to the current era, given the changes in reprocessing techniques and membranes [12].

Three studies were published subsequent to the meta-analysis with disparate results, possibly also reflecting differences in reprocessing techniques:

●A large United States dialysis organization performed a sophisticated analysis of patient survival in centers that practiced reuse [63]. A time-dependent survival analysis suggested a slight survival advantage with reuse, which may have been neutralized in patients who underwent a high number of reuses. Nonetheless, reuse was not associated with an increased mortality and led to significant reduction in high-risk medical waste. Since then, that same organization has discontinued reuse, probably for economic reasons.

●By contrast, a prospective, crossover study was performed among 23 hemodialysis facilities in the United States that were abandoning the practice of reuse [64]. Survival models were used to compare mortality in the six months before and after the facility changeover (with a three-month wash-out period). Compared with reuse, single-use dialysis was associated with a lower mortality in this study (adjusted hazard ratio of 0.74).

A suggested reason for the increased mortality associated with reuse in this study was the exclusive use of peracetic acid rather than formaldehyde for disinfection in the reuse group. Earlier observational studies had suggested that reuse with peracetic acid, but not formaldehyde, increased mortality [13,55]. As an example, in a report that used data from the Health Care Financing Administration/Centers for Disease Control (HCFA/CDC) database, reuse with peracetic acid in freestanding units was associated with a higher mortality than was reuse with formaldehyde or no reuse [55]. Unlike formaldehyde (which has higher vapor pressure), peracetic acid requires contact with surfaces for disinfection. Since publication of this study, the US Food and Drug Administration (FDA) demanded more stringent instructions for the use of peracetic acid [12].

●A subsequent study that analyzed nearly 50,000 incident hemodialysis patients in the 1998 to 1999 period, with follow-up through the end of the year 2000, found that reuse practices had no effect on survival, possibly reflecting improved practices of reprocessing with peracetic acid [60].

●A report from a reuse program in Thailand described using citrate dialysate, which allowed avoidance of systemic heparin [65]. The reuse performance was not diminished by avoiding heparin.

INFORMED CONSENT — There are no federal laws in the United States that require informed patient consent before reusing a dialyzer. However, the Health Care Financing Administration (HCFA) requires that patients be fully informed about their care [12]. In practice, consent is usually obtained in the United States. We agree with the National Kidney Foundation task force that each patient should be informed of the potential risks and advantages of dialyzer reuse and given an active role in ensuring that the correct dialyzer is in place before hemodialysis begins [66].

SUMMARY AND RECOMMENDATIONS

●Overview – Hemodialyzer reuse refers to the practice of using the dialyzer multiple times for a single patient. It is used largely for cost containment in areas of limited resources. In the United States and most resource-rich countries, reuse is rarely practiced. (See 'Introduction' above.)

●Reprocessing techniques – The basic procedure for dialyzer reprocessing involves four steps: rinsing, cleaning, performance testing, and disinfection/sterilization. Reprocessing dialyzers for reuse may be done by automated or manual methods. Meticulous adherence to an established protocol and following published recommendations are essential to ensure safety of the procedure. (See 'Reprocessing techniques' above.)

●Risks with reuse – There are three major concerns with reuse: the risk of infection to patients or staff, loss of performance with impairment in clearance and/or ultrafiltration, and exposure of patients or staff to germicide.

•Infection risk – Providing guidelines are followed and care is taken to prevent cross usage of dialyzers, there is no increased risk of viral hepatitis or human immunodeficiency virus (HIV) transmission to patients or dialysis personnel. (See 'Infection risk' above.)

•Loss of performance – Dialyzer performance decreases with increasing number of reuses. The rate at which this happens depends on the type of cleaning agents used for reprocessing, as well as membrane type. Dialyzer clotting also decreases dialyzer performance with reuse. The performance of the dialyzer should be closely monitored. (See 'Loss of performance' above.)

•Germicide exposure – Adverse patient and staff reactions to chemical disinfectants are rare if meticulous technique is followed. Among staff, allergic reactions to formaldehyde may occur. Among patients, chronic exposure to formaldehyde has been associated with formation of antibodies. (See 'Germicide exposure' above.)

●Clinical outcomes – Reuse does not appear to affect mortality, providing good technique is followed. However, good randomized trials are not available. (See 'Clinical outcomes with reuse' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Doug Schram, MD, and William L Henrich, MD, MACP, who contributed to earlier versions of this topic review.

The UpToDate editorial staff also acknowledges Gerald Schulman, MD, FASN, now deceased, who contributed to an earlier version of this topic.