I. PRODUCT WATER FOR HEMODIALYSIS. Patients are exposed to 120-200 L of dialysis solution during each dialysis treatment. Any small molecular weight contaminants in the dialysis solution can enter the blood unimpeded and accumulate in the body in the absence of renal excretion. Therefore, the chemical and microbiologic purity of dialysis solution is important if patient injury is to be avoided. Dialysis solution is prepared from purified water (product water) and concentrates, the latter containing the electrolytes necessary to provide dialysis solution of the prescribed composition. Most concentrates are obtained from commercial sources and their purity is subject to regulatory oversight. The purity of the water used to prepare dialysis solution or to reconstitute concentrates from powder at a dialysis facility, is the responsibility of the dialysis facility.

A. Water contaminants harmful to dialysis patients. Some substances added to municipal water supplies for public health reasons pose no threat to healthy individuals at the concentrations used, but can cause injury to renal failure patients if these substances are allowed to remain in the water used for dialysis. Therefore, all municipal water supplies should be assumed to contain substances harmful to dialysis patients, and all dialysis facilities require a system for purifying municipal water before it is used to prepare dialysis solution. What follows is a short list of the most common offending substances. Please refer to Suggested Readings for a more complete discussion of these and other contaminants.

1. Aluminum. This is added to water as a flocculating agent by many municipal water suppliers (aluminum sulfate is used to remove nonfilterable suspended particles). Aluminum causes bone disease, a progressive and often fatal neurologic deterioration known as the dialysis encephalopathy syndrome, and anemia.

2. Chloramine. This is added to water to prevent bacterial proliferation. Chloramine causes hemolytic anemia.

3. Fluoride. This is added to water supplies to reduce tooth decay. Large amounts of fluoride can elute into water from
an exhausted deionizer and cause severe pruritus, nausea, and fatal ventricular fibrillation.

4. Copper and zinc. These can leach from metal pipes and fittings and cause hemolytic anemia. Lead and aluminum can enter the water stream in a similar fashion.

5. Bacteria and endotoxin. The water used to prepare dialysis solution and the final dialysis solution are both susceptible to microbiologic contamination by bacteria and their endotoxins. Endotoxins, endotoxin fragments, and other bacterial products, such as short bacterial DNA fragments, some of which can be as small as 1,250 Da, can cross dialyzer membranes and enter the bloodstream to produce pyrogenic reactions and other untoward effects. The substances added to municipal water to suppress bacterial proliferation are removed by a dialysis facility’s water purification system, increasing the importance of preventing bacterial growth in the purified water.

6. Toxins from blue-green algae. Contamination of municipal water supplies by other microbial products, such as microcystins derived from blue-green algae, can also prove toxic to hemodialysis patients (Carmichael, 2001). Dialysis centers should be aware of the potential presence of such toxins, particularly in areas subject to seasonal algae blooms.

B. Water and dialysis solution quality requirements

1. Fluid quality standards. The International Organization for Standardization (ISO) has developed minimum standards for the purity of the water used to prepare dialysis solution and the purity of the final dialysis solution. These standards have been adopted by the Association for the Advancement of Medical Instrumentation as national standards for the United States and are also followed by regulatory organizations in many other countries. The standards set maximum levels for chemicals known to be toxic to hemodialysis patients, for chemicals known to be toxic to the general population, and for bacteria and their endotoxins.

Current recommendations are that product water used to prepare dialysis solution should contain 100 colony-forming units (CFU)/mL of bacteria and 0.25 endotoxin units (EU)/mL of endotoxin. The maximum levels for the final dialysis solution are 100 CFU/mL and 0.5 EU/mL, respectively. Pyrogenic reactions do not occur when levels of bacteria and endotoxins in the dialysis solution are maintained below these limits.

2. Ultrapure dialysis solution. Low levels of endotoxins and endotoxin fragments in dialysis solution, while not causing pyrogenic reactions, may contribute to a chronic inflammatory response that may be associated with long-term morbidity in dialysis patients. In observational studies, the use of so-called “ultrapure” dialysis solution, which is characterized by a bacteria level below 0.1 CFU/mL and endotoxin level below 0.03 EU/mL, has been
linked to reduced plasma levels of C-reactive protein and interleukin-6, an improved response of anemia to erythropoietin therapy, better nutrition as evidenced by increases in plasma albumin value, and higher estimated dry body weight, midarm muscle circumference, and urea nitrogen appearance rate. Ultrapure dialysis solution has also been associated with reduced plasma levels of β₂-microglobulin and pentosidine (a surrogate marker of carbonyl stress), a slower loss of residual renal function, and lower cardiovascular morbidity (Susantitaphong, 2013).

Although not all of the above benefits have been fully confirmed, many authorities believe that ultrapure dialysis solution should be used routinely. While use of ultrapure dialysis solution is highly desirable for hemodialysis, it is mandatory for online convective therapies such as online hemodiafiltration (see Chapter 17), which would otherwise increase transfer of bacterial fragments from dialysis/replacement solution to the blood.

C. Methods of purifying water for hemodialysis. Systems used to purify water for dialysis consist of three parts: pretreatment, primary purification, and distribution to the point of use.

1. Pretreatment. These components usually include a valve to blend hot and cold water to a constant temperature, some form of preliminary filtration, softening, and filtration through activated carbon. This cascade is designed to prepare the water for optimal operation of the primary purification process. Correction of pH (using injection of hydrochloric acid) is sometimes needed to correct excessive alkalinity, which can impede the ability of carbon beds to remove chlorine and chloramine and can cause fouling of reverse osmosis (RO) membranes by calcium and magnesium salts.

a. Water softener. A water softener is used to remove calcium and magnesium from water by exchange for sodium bound ionically to a resin bed. The resin exchanges Na⁺ ions for Ca⁺⁺ and Mg⁺⁺ as well as for other cations such as iron and manganese. The water softener protects the downstream RO membrane from scaling by calcium and magnesium in the source water. Such mineral scale can foul an RO membrane quickly. Water softener resins need to be backwashed and regenerated frequently on a routine basis using a concentrated sodium chloride solution (brine). During backwash, water is drawn into the softener in a reverse direction to wash and fluff the resin, and then the brine solution is introduced to regenerate the resin, replacing the recently bound Ca⁺⁺ and Mg⁺⁺ ions with Na+ ions.

b. Carbon. Activated carbon is utilized to remove chlorine and chloramine, which are not removed by RO. Carbon also removes other small organic compounds that may be in the water. Chlorine can combine with organic
substances in the water to form potentially cancer-causing compounds. As a consequence, many municipalities that previously used chlorine to suppress bacterial proliferation have changed over to using chloramine. The kinetics of the reaction through which carbon removes chloramine from water are slower than those for the removal of chlorine so that systems that adequately removed chlorine might not adequately remove chloramine. Chlorine or chloramine can permanently damage the downstream RO membrane. Importantly, chloramine can cause hemolytic anemia, and so this part of the water purification process needs to be monitored extremely closely. In the past, some municipalities did not notify dialysis units of the change from chlorine to chloramine in the water supply, and outbreaks of hemolytic anemia have been reported in the course of such changeovers.

Because of the critical need to remove chloramine and related organics, the water stream is run through two carbon beds in series. The upstream “worker” carbon bed will become exhausted first. The downstream or “polisher” carbon bed is used as a backup. This strategy permits sequential replacement as the upstream carbon bed becomes exhausted. Any exhausted carbon bed tank needs to be replaced as soon as possible. Although the levels of chlorine and chloramine can be determined separately, it is simpler to measure total chlorine—the sum of chlorine and chloramine—and replace exhausted carbon beds based on that measurement. If the municipal water contains chloramine, the total chlorine level in the water exiting the primary “worker” carbon bed needs to be checked before each dialysis shift. If breakthrough is noted, the total chlorine level should be checked downstream of the “polisher” bed. If no breakthrough is noted at that point, treatments can be continued while closely monitoring the outflow from the downstream “polisher” carbon bed. If total chlorine breakthrough is noted downstream of the “polisher” bed, treatments must cease immediately.