SlideShare une entreprise Scribd logo
1  sur  9
Télécharger pour lire hors ligne
Hemodialysis International 2007; 11:S18–S25




                       Worldwide water standards for
                               hemodialysis

                                                   Richard A. WARD
                      Department of Medicine, University of Louisville, Louisville, Kentucky, U.S.A.


      Abstract
      Contaminants commonly found in tap water are toxic to hemodialysis patients. To prevent patient
      injury from these contaminants, standards for the quality of water used to prepare dialysate have
      been developed. These standards are in general agreement concerning maximum allowable levels of
      inorganic chemical contaminants known to have adverse consequences for dialysis patients. There
      is less agreement about inorganic chemical contaminants that may be toxic, and most standards
      omit any requirements for organic chemical contaminants. There are considerable differences be-
      tween standards regarding the maximum allowable levels of microbiological contaminants, as well
      as the methods to be used for measuring them. Harmonization of existing standards may improve
      patient protection by promoting demonstrated best practices. Harmonization will require innovation
      and compromise to produce a standard that is widely applicable, provides patients with the neces-
      sary safeguards, and whose requirements can be routinely achieved within the constraints imposed
      by local reimbursement practices.

      Key words: Hemodialysis, water, standards, harmonization




INTRODUCTION                                                   patients developed symptoms of hypercalcemia.3 Recog-
                                                               nizing that these problems were related to high levels
When hemodialysis was first introduced as a treatment
                                                               of calcium in the municipal water, nephrologists began
for end-stage renal failure in the 1960s, dialysate was
                                                               treating the municipal water with a softener before it was
formulated by adding various salts, and often glucose, to      used to prepare dialysate.2,3
tap water. Once the more pressing technical challenges of
                                                                  By the mid-1970s, aluminum, chloramines, copper,
dialysis, such as blood access, were addressed and pa-
                                                               and fluoride had been identified as being definitely or
tients began to survive for longer times and in greater
                                                               probably toxic to hemodialysis patients.1 For aluminum
numbers, it became apparent that dialysate prepared from
                                                               and chloramines, this toxicity was evident at concentra-
tap water could contain substances that were harmful to
                                                               tions commonly found in municipal water supplies. In
hemodialysis patients or that caused problems with he-
                                                               addition, the incidence of pyrogenic reactions during
modialysis machines.1 As these substances were identi-
                                                               hemodialysis was observed to correlate with the level of
fied, individual nephrologists began to change their            bacteria in the dialysate.4 Thus, it was clear that the water
practices. For example, in areas where municipal water
                                                               used to prepare dialysate needed purification to ensure
supplies contained high levels of calcium and magnesium
                                                               low levels of these contaminants. This realization was the
(hard water), the fluid pathways of dialysis machines
                                                               start of the development of fluid quality standards for
became fouled with carbonate precipitates2 and some
                                                               hemodialysis, a process that continues to the present day.
                                                               The purpose of this paper is to review the evolution of
Correspondence to: R. A. Ward, PhD, Kidney Disease             quality standards for water used in hemodialysis applica-
Program, University of Louisville, 615 S. Preston Street,      tions and discuss some of the issues that may influence
Louisville, KY 40202-1718, U.S.A.                              the development of these standards at the beginning of
E-mail: richard.ward@louisville.edu                            the 21 century.


S18                              r 2007 The Authors. Journal compilation r 2007 International Society for Hemodialysis
Worldwide water standards for hemodialysis



In the beginning . . .                                          Protection Agency’s National Interim Primary Drinking
                                                                Water Standard published in 1975, which set maximum
The idea of a quality standard for water used in hemo-          contaminant levels for substances that had been deter-
dialysis appears to have been considered first in the            mined to be hazardous to the health of the general popu-
United States in the late 1960s, when the Association           lation. Because hemodialysis patients have a much greater
for the Advancement of Medical Instrumentation (AAMI)           exposure to water than a person with normal renal func-
and the American Society for Artificial Internal Organs          tion, because the gradient for transfer from dialysate to
(ASAIO) began a collaborative effort to write a standard        blood may be maintained throughout dialysis because of
for hemodialysis machines. A tentative draft of that stand-     protein binding, and because hemodialysis patients lack
ard was published for comment in 1970. This initial draft       renal excretion, the maximum allowable levels for these
suggested that the quality of water used to prepare dial-       substances was set at one-tenth of the EPA maximum al-
ysate should meet the requirements of the United States         lowable level for drinking water or the no-transfer level.
Pharmacopoeia for purified water, with an additional             (The no-transfer level for a solute is defined as that dial-
limit on heavy metals (o0.01 mg/L) and a minimum re-            ysate concentration at which there will be no net transfer
sistivity of 1 MO cm at 25 1C if deionized water was used.      of the solute across the dialyzer membrane, given a nor-
This draft underwent numerous revisions over the next 9         mal plasma concentration of the solute.) The maximum
years, and it was not until 1979 that the AAMI Renal            allowable level of bacteria in the water was based on the
Disease and Detoxification Committee finally reached              observation that the incidence of pyrogenic reactions was
agreement on its content. About the same time, Prakash          significantly increased if the level of bacteria in the dial-
Keshaviah at the Minneapolis Medical Research Founda-           ysate exceeded 2000 CFU/mL.4 Experience suggested that
tion, under contract to the United States Food and Drug         dialysis machines in use at the time the standard was
Administration, was preparing a report identifying the          being developed could amplify the bacterial burden in the
risks and hazards associated with conventional hemodi-          water by a factor of 10. Therefore, the maximum allow-
alysis systems. Because of the potential overlap between        able level of bacteria in the water was set at 200 CFU/mL.
these 2 endeavors, the AAMI Renal Disease and Detoxi-
fication Committee decided to wait for Keshaviah’s report        Current water quality standards and
before finalizing their standard. Keshaviah’s report ap-
peared in June 19805 and many of its recommendations
                                                                recommendations
were incorporated into the first AAMI standard for he-           In the years since the AAMI standard was first published,
modialysis systems, which was finally published in May           many other countries have established standards or rec-
1982.6 A parallel effort took place in Canada, with the         ommendations for the quality of water used in hemo-
Canadian Standards Association publishing a draft stand-        dialysis. These standards and recommendations have
ard (CSA Standard Z364.2) in 1978.                              been prepared by standards organizations (e.g., Canadi-
   The AAMI standard established maximum levels of a            an Standards Association,7 American National Standards
range of chemical contaminants and bacteria in the water        Institute/AAMI,8 International Organization for Standard-
used to prepare dialysate (Tables 1 and 2), as well as a        ization [ISO]9), pharmacopoeias (e.g., Europe,10 United
maximum level of bacteria in the final dialysate. The            States11), and professional associations (e.g., European
water quality requirements of the Canadian standard             Renal Association-European Dialysis and Transplant
were substantially the same as those in the AAMI stand-         Association [ERA-EDTA],12 Japanese Society for Dialysis
ard. The substances covered by these standards could be         Therapy13). While there is general agreement concerning
divided into 4 groups (Tables 1 and 2): substances with         the maximum allowable levels of inorganic chemicals
documented toxicity in hemodialysis patients; substances        with documented toxicity in hemodialysis patients (alu-
normally included in dialysate; other trace elements; and       minum, chloramines, copper, fluoride, lead, nitrate, sul-
microbiological contaminants. For substances with doc-          fate, and zinc), there are some exceptions. For example,
umented toxicity in hemodialysis patients, the maximum          the current edition of the European Pharmacopoeia does
levels were set at values less than the lowest level at which   not explicitly specify maximum allowable levels for cop-
toxicity had been documented. For substances normally           per or chloramines. In the latter case, the European Phar-
included in dialysate, the maximum levels were set so that      macopoeia does specify a maximum allowable level for
the water would not significantly affect the final dialysate      total available chlorine and provides a test method that
composition. The other trace elements included in the           will detect both free chlorine and chloramines.10 As the
standard were based on the United States Environmental          maximum allowable level for total available chlorine is set


Hemodialysis International 2007; 11:S18–S25                                                                            S19
Ward



Table 1 Recommended maximum concentrations of chemical contaminants in water used for hemodialysis

                                                       Canadian Standards            United States               European
Contaminant (mg/L)                   AAMI8                Association7              Pharmacopoeia11           Pharmacopoeia10
Substances with documented toxicity in hemodialysis patients
  Aluminum                          0.01                  0.01                            0.01                      0.01
  Chloramines                       0.10                  0.10                            0.10                       —
  Free chlorine                     0.50                   —                              0.50                       —
  Total available chlorine           —                     —                               —                        0.1
  Copper                            0.10                  0.10                            0.10                       —
  Fluoride                          0.20                  0.20                            0.20                      0.20
  Lead                              0.005                 0.005                           0.005                      —
  Nitrate (as N)                    2.00                  2.00                            2.00                      2.00
  Sulfate                        100                    100                             100                        50
  Zinc                              0.10                  0.10                            0.10                      0.10
Substances normally included in dialysate
  Calcium                           2                     2                                2                        2
  Magnesium                         4                     4                                4                        2
  Potassium                         8                     8                                8                        2
  Sodium                          70                     70                               70                       50
Other substances
  Ammonia                            —                     —                                —                       0.2
  Antimony                          0.006                 0.006                            0.006                     —
  Arsenic                           0.005                 0.005                            0.005                     —
  Barium                            0.10                  0.10                             0.10                      —
  Beryllium                         0.0004                0.0004                           0.0004                    —
  Cadmium                           0.001                 0.001                            0.001                     —
  Chromium                          0.014                 0.014                            0.014                     —
  Chloride                           —                     —                                —                      50
  Mercury                           0.0002                0.0002                           0.0002                   0.001
  Selenium                          0.09                  0.09                             0.09                      —
  Silver                            0.005                 0.005                            0.005                     —
  Thallium                          0.002                 0.002                            0.002                     —
  Total heavy metals                 —                     —                                —                       0.10
  Total organic carbon               —                    0.500                             —                        —
AAMI =Association for the Advancement of Medical Instrumentation.


at the same value as other standards set for chloramines,           modialysis water standard because there were no data
there is effectively no difference in quality requirements.         documenting their toxicity in hemodialysis patients. The
In addition, there are some differences in how the various          extent to which standards for water used in dialysis ap-
standards treat heavy metals and substances normally in-            plications should continue to be influenced by drinking
cluded in dialysate (magnesium, potassium, and sodium;              water standards remains an open question as discussed
Table 1). Some standards (Canada, United States, ISO)               later in this review. Overall, and with the exception of the
specify limits for individual heavy metals, while others            omission of copper from the European Pharmacopoeia,
(European Pharmacopoeia) set a limit for heavy metals as            there is no compelling evidence of adverse clinical con-
a group. Also, the range of heavy metals included in the            sequences arising from the minor differences between
standards has evolved over time. Three additional heavy             standards in the allowable levels of inorganic chemical
metals (antimony, beryllium, and thallium) were added to            contaminants.
the AAMI standard in 2001 by virtue of their inclusion in              Of note, none of the existing standards and recom-
the United States drinking water standard. The AAMI Re-             mendations includes limits for specific organic chemical
nal Disease and Detoxification Committee expressed                   contaminants. The rationale for this omission is that or-
some hesitation about adding these elements to their he-            ganic chemicals with specific toxicity to hemodialysis


S20                                                                                Hemodialysis International 2007; 11:S18–S25
Worldwide water standards for hemodialysis



Table 2 Recommended maximum levels of microbiological             able levels of microbiological contaminants in water used
contaminants in water used for hemodialysis                       for hemodialysis. These differences involve not only the
                                                                  levels of microbiological contaminants (Table 2) but also
                                       Bacteria     Endotoxin     the methods used to measure them (Table 3). The original
                                      (CFU/mL)       (EU/mL)      AAMI standard set a maximum allowable level for bac-
AAMI8                                    200           2          teria of 200 CFU/mL. Subsequently, other stand-
Canadian Standards Association7          100           2          ards7,10,11,16 and recommended practices12,17 set the
United States Pharmacopoeia11            100           2          level at 100 CFU/mL, which is not substantially different
European Pharmacopoeia10                 100           0.25
                                                                  from 200 CFU/mL, given the variability inherent in using
Swedish Pharmacopoeia16                  100           0.25
                                                                  plate counts to determine bacterial levels. As discussed
ERA-EDTA12a                              100           0.25
Japanese Society for                      —            0.25       later, however, there may actually be significant differen-
   Dialysis Therapy13                                             ces in the allowable level of bacteria, depending on what
Italian Society of Nephrology17a         100           0.25       culturing methods are specified. The original AAMI
a
                                                                  standard did not set a limit for endotoxin because, at
 Both the ERA-EDTA and the Italian Society of Nephrology recom-
                                                                  that time, no convenient test for endotoxin was available.
mend that all dialysis facilities aim for ultrapure dialysate.
AAMI =Association for the Advancement of Medical Instrumenta-     In 2001, the AAMI standard was revised to include a
tion; ERA-EDTA = European Renal Association-European Dialysis     maximum allowable level of endotoxin of 2 EU/mL meas-
and Transplant Association.                                       ured using the Limulus amebocyte lysate assay. This change
                                                                  took place after a lengthy debate about whether or not
                                                                  there was sufficient clinical evidence to support inclusion
                                                                  of a maximum allowable level of endotoxin. This cautious
patients have not been identified and that carbon adsorp-          approach is in marked contrast to the position taken in
tion and reverse osmosis should remove most organic               Europe and Japan, where a considerably lower maximum
compounds. That hemodialysis patients may be at risk              allowable level of endotoxin (0.25 EU/mL) was intro-
from organic compounds is evidenced, however, by re-              duced during the 1990s. Indeed, many authorities advo-
cent reports from Italy describing contamination of water         cate even lower maximum allowable levels for bacteria
by organo-halogenated compounds that were not re-                 and endotoxin (0.1 CFU/mL and 0.03 EU/mL, respective-
moved by standard hemodialysis water treatment prac-              ly), although so far these levels remain recommendations,
tices,14,15 including the use of activated carbon and             rather than requirements. Fluids meeting this more rig-
reverse osmosis. The Canadian standard7 does include a            orous quality standard are referred to as ‘‘ultrapure.’’18
maximum allowable level for total organic carbon                  Low levels of endotoxin and other bacterial products in
(0.5 mg/L); however, it is not clear that meeting this re-        dialysate have been implicated in the low-level chronic
quirement would protect against toxic levels of many or-          inflammation observed in hemodialysis patients. Use of
ganic compounds.                                                  ultrapure fluids is believed to ameliorate this inflamma-
   In contrast to chemical contaminants, there are signif-        tion and delay or reduce the severity of long-term com-
icant differences in the recommended maximum allow-               plications of hemodialysis therapy, such as malnutrition,

Table 3 Recommended method for determining bacterial levels in water used for hemodialysis

                                                                                      Incubation                     Incubation
                                                  Culture medium                   temperature ( 1C)                  time (hr)
AAMI8                                             TSA                                  35 to   37                            48
Canadian Standards Association7                   TSA, SMA, R2A                        35                                    48
United States Pharmacopoeia11                     TSA                                  30 to   35                           48
European Pharmacopoeia10                          R2A                                  30 to   35                           120
Swedish Pharmacopoeia16                           TGEA                                 22                                  120
ERA-EDTA12a                                       R2A                                  20 to   22                           144
Italian Society of Nephrology17a                  TGEA, R2A                            20 to   23                    120 to 144
a
 Both the ERA-EDTA and the Italian Society of Nephrology recommend that all dialysis facilities aim for ultrapure dialysate.
AAMI =Advancement of Medical Instrumentation; ERA-EDTA = European Renal Association-European Dialysis and Transplant Association;
R2A = Reasoner’s 2A; SMA = standard methods agar; TGEA = tryptone glucose extract agar; TSA = tryptic soy agar.



Hemodialysis International 2007; 11:S18–S25                                                                                S21
Ward



b2-microglobulin amyloidosis, resistance to erythropoie-         best practices and a standard that is enforced as a regu-
tin, and loss of residual renal function.19                      lation. Both models, as well as various hybrid versions,
   In addition to differences in the maximum allowable           are currently in use around the world. For example, in
levels of endotoxin, there are important differences             the United States, compliance with the AAMI standard
between standards in the methods recommended for                 for water quality is required if a facility is to receive pay-
measuring bacterial contamination. The original AAMI             ment for hemodialysis services from the United States
standard allowed the use of tryptic soy agar (TSA), stand-       Government’s Medicare program and compliance is
ard methods agar (SMA), or blood agar, with enumeration          monitored by periodic inspections of dialysis facilities.
of colonies after incubation for 48 hr at 37 1C.6 It was         In contrast, compliance with standards is either not
soon realized that the nutrient-rich environment pro-            required or not enforced by inspection in many other
vided by blood agar was not appropriate for culturing            jurisdictions. A quality standard enforced as a regulation
organisms adapted to a purified water environment and             must be capable of being met routinely by a typical dia-
the use of blood agar was eliminated as an option in sub-        lysis facility at a cost consistent with local reimbursement
sequent versions of the standard.8 Later studies also            practices. In contrast, a standard intended as a guide to
showed that the combination of TSA and incubation at             best practices may recommend a level of quality that can
37 1C for 48 hr was not optimal for recovery of water-           be met only by commitment of additional resources at the
borne organisms. Use of nutrient-poor media, such as             discretion of an individual dialysis facility that believes
Reasoner’s 2A and tryptone glucose extract agar, and             that level of quality will be of benefit to its patients. A
longer incubation times at room temperature resulted in          harmonized standard should be capable of serving both
colony counts that were often an order of magnitude              functions.
higher than those obtained with TSA incubated for 48 hr             It may be possible for a standard to serve both a regu-
at 37 1C.18 These more stringent culturing conditions            latory and an advisory role by including 2 grades of water
have been adopted in whole, or in part, by several or-           quality in the standard. The first grade would establish
ganizations issuing standards or recommendations for the         maximum allowable concentrations of contaminants
quality of water used for hemodialysis (Table 3).                based on definitive evidence that higher concentrations
                                                                 of a contaminant would be harmful to patients. The sec-
                                                                 ond grade may recommend a lower concentration of a
Where do we go from here?                                        contaminant where there was a suggestion that the lower
Some in the dialysis community believe that the time is          concentration may be associated with improved patient
right to harmonize existing quality standards for water          outcomes. This approach has been used by the ERA-
used in hemodialysis applications. It is suggested that a        EDTA and the Italian Society of Nephrology, which have
harmonized standard would help disseminate demon-                adopted the European Pharmacopoeia quality standard
strated best practices in countries with well-established        for maximum allowable levels of contaminants, but rec-
hemodialysis programs, thereby decreasing the likelihood         ommend the use of ultrapure fluids.12,17
of both acute and chronic adverse events related to water           As is evident from Tables 1 and 2, there are some dif-
quality. It could also serve as a guideline for countries        ferences in the range of contaminants included in the
where chronic hemodialysis is still in its infancy. Finally, a   various standards and recommendations, as well as in the
harmonized standard may contribute to better technology          maximum allowable level of individual contaminants. A
for water purification and distribution by establishing           harmonized standard would require a resolution of these
a consistent set of expectations for equipment manufac-          differences.
turers. Current efforts to revise and expand the ISO’s              As mentioned previously, some current standards do
standards related to fluids used for hemodialysis may act         not explicitly include chloramines even though their tox-
as an impetus to harmonization. Before harmonization             icity in hemodialysis patients has been documented re-
can occur, however, 2 important questions must be an-            peatedly over 30 years.20,21 It has been argued that there
swered: Is harmonization desirable and feasible; and, how        is no need to include chloramines in a standard for a
should the maximum allowable levels of contaminants be           region where chloramines are not used to disinfect
determined?                                                      municipal water supplies. However, patient injury has
   The desirability and feasibility of harmonizing water         occurred in many parts of the world when municipal
quality standards depend, in part, on how such standards         water providers began using chloramines with little or no
are used. There is a significant difference between a            prior notice to dialysis facilities. For this reason, it seems
standard used to provide guidance on demonstrated                reasonable that a harmonized standard should include all


S22                                                                              Hemodialysis International 2007; 11:S18–S25
Worldwide water standards for hemodialysis



contaminants with documented toxicity in hemodialysis         about the strength of the evidence for strontium toxicity
patients. The benefits of avoiding toxicity almost certainly   and the concentration at which it occurs.
outweigh the cost of routine monitoring for these con-           Microbiological contaminants present a particular
taminants.                                                    problem in trying to reach consensus on maximum al-
   Whether or not to include contaminants that have no        lowable levels of contaminants. As described earlier, cur-
documented toxicity in hemodialysis patients is a more        rent standards differ significantly in the maximum
difficult question. Heavy metals were included in the ori-     allowable level of endotoxin. Further, even though there
ginal AAMI standard because their levels in drinking          does not appear to be a large difference in plate count
water were regulated as a matter of public health and         values, in reality, there may be significant differences in
because they were thought to pose a greater risk to he-       the maximum allowable level of bacteria because of dif-
modialysis patients because of the mechanism of expos-        ferences in recommended culturing methods. In general,
ure and the lack of renal excretion. Other standards have     European and Japanese standards set a lower maximum
chosen to deal with heavy metals collectively by estab-       allowable level for endotoxin than the United States
lishing a maximum allowable level for them as a group.        standard (Table 2). In addition, there is widespread sup-
Neither approach is entirely satisfactory. Including a sub-   port for the use of ultrapure fluids in both Europe and
stance in the standard because it is included in drinking     Japan, based on a growing literature showing improve-
water regulations implies that any substance added to the     ments in outcomes such as nutrition and anemia correc-
drinking water regulations should be added to the he-         tion when ultrapure dialysate is used. Some in the United
modialysis water standard. This situation has arisen in the   States dialysis community argue, however, that the evi-
United States, leading to the addition of antimony, beryl-    dence used to support lower levels of endotoxin and, in
lium, and thallium to the hemodialysis water standard in      particular, ultrapure dialysate is not convincing. They cite
2001 even though there was no evidence that they posed        the absence of controlled clinical trials comparing out-
a particular risk to hemodialysis patients. This open-        comes obtained with lower levels of endotoxin, including
ended, non-evidence-based approach only serves to in-         ultrapure dialysate, with those obtained with dialysate
crease the cost and complexity of monitoring water for        meeting the current United States quality standards. They
hemodialysis without any apparent benefit to patients.         also worry about the cost and feasibility of routinely
Combining the heavy metals into a single group is attrac-     meeting a more stringent quality standard in a regulated
tive as it has the potential to reduce the cost of routine    environment where reimbursement is tightly controlled.
water analyses. However, treating heavy metals as a           With regard to water, these arguments may be somewhat
group implies that the maximum allowable level for            moot. It should be remembered that patients are treated
the group should not exceed the maximum allowable             with dialysate, not water, and it is the microbiological
level for the most toxic member of that group. Cur-           quality of the dialysate that is important. In general, ultra-
rently, maximum allowable levels for 10 heavy metals          pure dialysate is prepared by point-of-use filtration of the
included in the standards that list each heavy metal          dialysate immediately before it enters the dialyzer. Clearly,
individually are below the 0.1 mg/L level set in the Eu-      higher quality water reduces the burden on the final ul-
ropean Pharmacopoeia for total heavy metals. At this          trafilter; however, currently available point-of-use ultra-
point, it remains unclear how best to deal with trace con-    filtration systems should be capable of producing
taminants, with no clearly defined toxicity in the setting     ultrapure dialysate from concentrates and water that rou-
of hemodialysis.                                              tinely meet any of the quality standards listed in Table 2.
   However this issue is resolved, an effective standard      Thus, the cost aspect of ultrapure dialysate shifts from
should incorporate a mechanism for promptly adding a          debate about whether or not the quality of the water
new substance that may, in the future, be shown to be         used to prepare the dialysate should be ultrapure to
toxic to hemodialysis patients. Although candidate toxins     whether or not to install point-of-use ultrafilters for the
are rare, examples have appeared in recent years. Lead,       final dialysate.
which was included in the original AAMI standard be-             All of these arguments are predicated on the assump-
cause its levels were regulated in drinking water, was re-    tion that endotoxin levels are an adequate measure of
ported recently to be toxic in hemodialysis patients,22       water quality. Endotoxin testing reveals nothing about the
although the level at which toxicity occurs is not well       levels of other microbiological contaminants, including
defined. Strontium contamination of water used to pre-         yeasts, fungi, peptidoglycans, and fragments of bacterial
pare dialysate has been implicated in bone disease in he-     DNA, all of which have been identified in water used for
modialysis patients,23,24 although there is still debate      hemodialysis.25–27


Hemodialysis International 2007; 11:S18–S25                                                                           S23
Ward



SUMMARY                                                           7 Canadian Standards Association. Water Treatment Equip-
                                                                    ment and Water Quality Requirements for Hemodialysis,
Hemodialysis patients are at risk from contaminants in              Z364.2.2-03. Toronto, ON: Canadian Standards Associa-
the water used to prepare dialysate. To mitigate this risk,         tion; 2003.
various organizations have developed standards and rec-           8 Association for the Advancement of Medical Instru-
ommendations for water quality over the past 25 years.              mentation. Water Treatment Equipment for Hemodialysis
There is general agreement concerning maximum allow-                Applications, ANSI/AAMI RD62:2001. Arlington, VA: As-
able levels of inorganic chemical contaminants known to             sociation for the Advancement of Medical Instrumenta-
have adverse consequences for dialysis patients. There is           tion; 2001.
less uniformity when it comes to inorganic chemical con-          9 International Organization for Standardization. Water for
taminants that may have toxicity and an almost complete             Haemodialysis and Related Therapies, ISO 13959:2002(E).
silence in the area of organic chemical contaminants.               Geneva: International Organization for Standardization;
Further, there are considerable differences between the             2002.
                                                                 10 European Pharmacopoeia Commission. European
various standards and recommendations regarding the
                                                                    Pharmacopoiea, 5th ed. Monograph 2005:1167, Haemodi-
maximum allowable levels of microbiological contamin-
                                                                    alysis Solution, Concentrated, Water for Diluting. Stras-
ants and the methods to be used for measuring these                 bourg: European Pharmacopoeia Commission; 2005.
contaminants. Harmonization of the various standards             11 United States Pharmacopoiea. h1230iWater for health
and recommended practices may help protect patients by              applications, water for hemodialysis. First supplement to
promoting demonstrated best practices and providing a               USP 28-NF 23, 2005.
road map for those countries where large-scale hemodi-           12 European Renal Association-European Dialysis and
alysis is still in its infancy. Achieving harmonization will        Transplant Association. European best practice guidelines
require innovation and compromise to produce a stand-               for haemodialysis (part I), section IV: Dialysis fluid purity.
ard that is widely applicable, provides patients with the           Nephrol Dial Transplant. 2002; 17(Suppl 7):45–62.
necessary safeguards, and whose requirements can be              13 Morii K, Morii H, Asano Y, Naitoh H, Takesawa S. Stand-
routinely achieved within the constraints imposed by                ard for safety of dialysis fluid. J Jpn Soc Dial Ther. 1998;
local reimbursement practices.                                      31:1107–1109.
                                                                 14 Formica M, Vallero A, Forneris G, et al. Organo-haloge-
                                                                    nated contamination of a dialysis water treatment plant.
                                                                    G Ital Nefrol. 2002; 19:479–482.
Manuscript received August 2006; revised September               15 Poli D, Pavone L, Tansinda P, et al. Organic contam-
2006.                                                               ination in dialysis water: Trichloroethylene as a model
                                                                    compound. Nephrol Dial Transplant. 2006; 21:1618–
                                                                    1625.
REFERENCES                                                                                        ¨                   ¨
                                                                 16 Swedish Pharmacopoeia. Lakemedelsstandard for Finland
 1 Ward RA. Water processing for hemodialysis. Part I: A            och Sverige (Preparation and Handling of Solutions for
   historical perspective. Semin Dial. 1997; 10:26–31.                                    ¨
                                                                    Haemodialysis). Lakemedelsverket: Svenska Far-
 2 Ivanovich P, Marr TA, Gothberg LA, Steury RE, Drake RF    .              ´         ´
                                                                    makopekommitten; 1997.
   A compact hydraulic proportioning system for hemodi-          17 Italian Society of Nephrology. Guidelines on water and
   alysis. Trans Am Soc Artif Int Organs. 1966; 12:357–359.         solutions for dialysis. G Ital Nefrol. 2005; 22:246–273.
 3 Freeman RM, Lawton RL, Chamberlain MA. Hard-water             18 Ledebo I, Nystrand R. Defining the microbiological qual-
   syndrome. N Engl J Med. 1967; 276:1113–1118.                     ity of dialysis fluid. Artif Organs. 1999; 23:37–43.
 4 Favero MS, Petersen NJ, Boyer KM, Carson LA, Bond             19 Ward RA. Ultrapure dialysate. Semin Dial. 2004; 17:
   WW. Microbial contamination of renal dialysis systems            489–497.
   and associated health risks. Trans Am Soc Artif Int Organs.   20 Ward DM. Chloramine removal from water used in he-
   1974; 20:175–183.                                                modialysis. Adv Renal Replac Ther. 1996; 3:337–347.
 5 Keshaviah P, Luehmann D, Shapiro F Comty CM. Inves-
                                          ,                      21 Ward RA. Dialysis water as a determinant of the ad-
   tigation of the Risks and Hazards Associated with Hemodi-        equacy of dialysis. Semin Nephrol. 2005; 25:102–111.
   alysis Devices. Silver Spring, MD: U.S. Department of         22 Kathuria P, Nair B, Schram D, Medlock R. Outbreak of
   Health, Education, and Welfare, Food and Drug Admin-             lead poisoning in a hemodialysis unit (abstract). J Am Soc
   istration; 1980.                                                 Nephrol. 2004; 15:617A.
 6 Association for the Advancement of Medical Instrumen-         23 Schrooten I, Elseviers MM, Lamberts LV, De Broe ME,
   tation. Hemodialysis Systems, ANSI/AAMI RD5-1981. Ar-            D’Haese PC. Increased serum strontium levels in dialysis
   lington, VA: Association for the Advancement of Medical          patients: An epidemiological survey. Kidney Int. 1999;
   Instrumentation; 1982.                                           56:1886–1892.


S24                                                                              Hemodialysis International 2007; 11:S18–S25
Worldwide water standards for hemodialysis



24 D’Haese PC, Schrooten I, Goodman WG, et al. Increased     26 Tsuchida K, Takemoto Y, Yamagami S, et al. Detection of
   bone strontium levels in hemodialysis patients with os-      peptidoglycan and endotoxin in dialysate, using silk-
   teomalacia. Kidney Int. 2000; 57:1107–1114.                  worm larvae plasma and limulus amebocyte lysate meth-
25 Klein E, Pass T, Harding GB, Wright R, Million C. Mi-        ods. Nephron. 1997; 75:438–443.
   crobial and endotoxin contamination in water and dial-    27 Schindler R, Beck W, Deppisch R, et al. Short bacterial
   ysate in the central United States. Artif Organs. 1990;      DNA fragments: Detection in dialysate and induction of
   14:85–94.                                                    cytokines. J Am Soc Nephrol. 2004; 15:3207–3214.




Hemodialysis International 2007; 11:S18–S25                                                                         S25
1  worlwide-water_standars_for_hemodialysis

Contenu connexe

Tendances

Environmental Risks from bulk chlorine rev 4 3 16
Environmental Risks from bulk chlorine rev 4 3 16Environmental Risks from bulk chlorine rev 4 3 16
Environmental Risks from bulk chlorine rev 4 3 16Nigel Harrison
 
Water issues
Water issuesWater issues
Water issuesGenieve1
 
Stormwater pond ppt (1)
Stormwater pond ppt (1)Stormwater pond ppt (1)
Stormwater pond ppt (1)jojotaguinod
 
Water Quality Managements Developments: Nutrients and Bacteria
Water Quality Managements Developments: Nutrients and BacteriaWater Quality Managements Developments: Nutrients and Bacteria
Water Quality Managements Developments: Nutrients and BacteriaSoutheast Chapter of Texas AWWA
 
THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...
THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...
THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...EDITOR IJCRCPS
 
Risks and Assessments of Cyanotoxins in Drinking Water
Risks and Assessments of Cyanotoxins in Drinking WaterRisks and Assessments of Cyanotoxins in Drinking Water
Risks and Assessments of Cyanotoxins in Drinking WaterRuben Diaz
 
Kenya; The Long Term Sustainability Of Household Bio-Sand Filtration
Kenya;  The Long Term Sustainability Of Household Bio-Sand FiltrationKenya;  The Long Term Sustainability Of Household Bio-Sand Filtration
Kenya; The Long Term Sustainability Of Household Bio-Sand FiltrationV9X
 
The International Journal of Engineering and Science (IJES)
The International Journal of Engineering and Science (IJES)The International Journal of Engineering and Science (IJES)
The International Journal of Engineering and Science (IJES)theijes
 
Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...
Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...
Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...Jeff Brown, PhD, CNMA
 
Treatment wetland report
Treatment wetland reportTreatment wetland report
Treatment wetland reportNicole Ng, EI
 
Emerging Pathogens In Wastewater
Emerging Pathogens In WastewaterEmerging Pathogens In Wastewater
Emerging Pathogens In Wastewatercrockettc
 
Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...
Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...
Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...IRJET Journal
 
Bacteria in Drinking water
Bacteria in Drinking waterBacteria in Drinking water
Bacteria in Drinking waterMirko Rossi
 
Lecture swimming water_vs2016
Lecture swimming water_vs2016Lecture swimming water_vs2016
Lecture swimming water_vs2016Mirko Rossi
 

Tendances (19)

Environmental Risks from bulk chlorine rev 4 3 16
Environmental Risks from bulk chlorine rev 4 3 16Environmental Risks from bulk chlorine rev 4 3 16
Environmental Risks from bulk chlorine rev 4 3 16
 
Water issues
Water issuesWater issues
Water issues
 
2009-02-17 Brine Disposal Alternatives
2009-02-17  Brine Disposal Alternatives2009-02-17  Brine Disposal Alternatives
2009-02-17 Brine Disposal Alternatives
 
8.15 tech 2
8.15 tech 28.15 tech 2
8.15 tech 2
 
Stormwater pond ppt (1)
Stormwater pond ppt (1)Stormwater pond ppt (1)
Stormwater pond ppt (1)
 
I0665256
I0665256I0665256
I0665256
 
Water Quality Managements Developments: Nutrients and Bacteria
Water Quality Managements Developments: Nutrients and BacteriaWater Quality Managements Developments: Nutrients and Bacteria
Water Quality Managements Developments: Nutrients and Bacteria
 
THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...
THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...
THE EFFECT OF WATER TREATMENT ON CALCIUM AND BERYLLIUM LEVELS OF WATER IN KAR...
 
Risks and Assessments of Cyanotoxins in Drinking Water
Risks and Assessments of Cyanotoxins in Drinking WaterRisks and Assessments of Cyanotoxins in Drinking Water
Risks and Assessments of Cyanotoxins in Drinking Water
 
Kenya; The Long Term Sustainability Of Household Bio-Sand Filtration
Kenya;  The Long Term Sustainability Of Household Bio-Sand FiltrationKenya;  The Long Term Sustainability Of Household Bio-Sand Filtration
Kenya; The Long Term Sustainability Of Household Bio-Sand Filtration
 
The International Journal of Engineering and Science (IJES)
The International Journal of Engineering and Science (IJES)The International Journal of Engineering and Science (IJES)
The International Journal of Engineering and Science (IJES)
 
Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...
Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...
Dr J N Brown - PhD thesis (2002) Partitioning of Chemical Contaminants in Urb...
 
Treatment wetland report
Treatment wetland reportTreatment wetland report
Treatment wetland report
 
Emerging Pathogens In Wastewater
Emerging Pathogens In WastewaterEmerging Pathogens In Wastewater
Emerging Pathogens In Wastewater
 
Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...
Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...
Water Quality Assessment through GIS: A Case Study of Sukhna Lake, Chandigarh...
 
Bacteria in Drinking water
Bacteria in Drinking waterBacteria in Drinking water
Bacteria in Drinking water
 
2013 Drinking Water Report
2013 Drinking Water Report2013 Drinking Water Report
2013 Drinking Water Report
 
Lecture swimming water_vs2016
Lecture swimming water_vs2016Lecture swimming water_vs2016
Lecture swimming water_vs2016
 
Dania Beach CCR 2013
Dania Beach CCR 2013Dania Beach CCR 2013
Dania Beach CCR 2013
 

En vedette

Product water and hemodialysis dialysis solution
Product water and hemodialysis dialysis solutionProduct water and hemodialysis dialysis solution
Product water and hemodialysis dialysis solutionIPMS- KMU KPK PAKISTAN
 
Metrics for hemodialysis quality care
Metrics for hemodialysis quality careMetrics for hemodialysis quality care
Metrics for hemodialysis quality careSteve Chen
 
Bacteriological analysis of drinking water by MPN method.
Bacteriological analysis of drinking water by MPN method.Bacteriological analysis of drinking water by MPN method.
Bacteriological analysis of drinking water by MPN method.prakashtu
 
Dialysis various modalities and indices used
Dialysis various modalities and indices usedDialysis various modalities and indices used
Dialysis various modalities and indices usedAbhay Mange
 
Quality Testing of Drinking Water
Quality Testing of Drinking WaterQuality Testing of Drinking Water
Quality Testing of Drinking Waterbill16388
 
Water treatment and quality control of dialysate.
Water treatment and quality control of dialysate.Water treatment and quality control of dialysate.
Water treatment and quality control of dialysate.Vishal Golay
 
10 Insightful Quotes On Designing A Better Customer Experience
10 Insightful Quotes On Designing A Better Customer Experience10 Insightful Quotes On Designing A Better Customer Experience
10 Insightful Quotes On Designing A Better Customer ExperienceYuan Wang
 
How to Build a Dynamic Social Media Plan
How to Build a Dynamic Social Media PlanHow to Build a Dynamic Social Media Plan
How to Build a Dynamic Social Media PlanPost Planner
 
Learn BEM: CSS Naming Convention
Learn BEM: CSS Naming ConventionLearn BEM: CSS Naming Convention
Learn BEM: CSS Naming ConventionIn a Rocket
 
SEO: Getting Personal
SEO: Getting PersonalSEO: Getting Personal
SEO: Getting PersonalKirsty Hulse
 

En vedette (11)

Paint
PaintPaint
Paint
 
Product water and hemodialysis dialysis solution
Product water and hemodialysis dialysis solutionProduct water and hemodialysis dialysis solution
Product water and hemodialysis dialysis solution
 
Metrics for hemodialysis quality care
Metrics for hemodialysis quality careMetrics for hemodialysis quality care
Metrics for hemodialysis quality care
 
Bacteriological analysis of drinking water by MPN method.
Bacteriological analysis of drinking water by MPN method.Bacteriological analysis of drinking water by MPN method.
Bacteriological analysis of drinking water by MPN method.
 
Dialysis various modalities and indices used
Dialysis various modalities and indices usedDialysis various modalities and indices used
Dialysis various modalities and indices used
 
Quality Testing of Drinking Water
Quality Testing of Drinking WaterQuality Testing of Drinking Water
Quality Testing of Drinking Water
 
Water treatment and quality control of dialysate.
Water treatment and quality control of dialysate.Water treatment and quality control of dialysate.
Water treatment and quality control of dialysate.
 
10 Insightful Quotes On Designing A Better Customer Experience
10 Insightful Quotes On Designing A Better Customer Experience10 Insightful Quotes On Designing A Better Customer Experience
10 Insightful Quotes On Designing A Better Customer Experience
 
How to Build a Dynamic Social Media Plan
How to Build a Dynamic Social Media PlanHow to Build a Dynamic Social Media Plan
How to Build a Dynamic Social Media Plan
 
Learn BEM: CSS Naming Convention
Learn BEM: CSS Naming ConventionLearn BEM: CSS Naming Convention
Learn BEM: CSS Naming Convention
 
SEO: Getting Personal
SEO: Getting PersonalSEO: Getting Personal
SEO: Getting Personal
 

Similaire à 1 worlwide-water_standars_for_hemodialysis

Calidad del agua para agricultura fao 29-ayers y westcot 1985-oki
Calidad del agua para agricultura fao 29-ayers y westcot 1985-okiCalidad del agua para agricultura fao 29-ayers y westcot 1985-oki
Calidad del agua para agricultura fao 29-ayers y westcot 1985-okiPIEDRON
 
The And Sustainability Of The Pioneer River Catchment
The And Sustainability Of The Pioneer River CatchmentThe And Sustainability Of The Pioneer River Catchment
The And Sustainability Of The Pioneer River CatchmentBrenda Torres
 
ARSENIC MITIGATION FOR SAFE GROUNDWATER
ARSENIC MITIGATION FOR SAFE GROUNDWATERARSENIC MITIGATION FOR SAFE GROUNDWATER
ARSENIC MITIGATION FOR SAFE GROUNDWATERSiti Mastura
 
Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...
Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...
Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...WinnaxTaclapII
 
Water quality and sampling
Water quality and samplingWater quality and sampling
Water quality and samplingJasmine John
 
Long Island's Drinking Water: Threats and Solutions
Long Island's Drinking Water:  Threats and SolutionsLong Island's Drinking Water:  Threats and Solutions
Long Island's Drinking Water: Threats and SolutionsSave The Great South Bay
 
Research paper
Research paperResearch paper
Research paper2baa
 
Canadian Se DWQG_Gilron
Canadian Se DWQG_GilronCanadian Se DWQG_Gilron
Canadian Se DWQG_GilronGuy Gilron
 
The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...
The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...
The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...Marwan Haddad
 
Water Quality Of Tap And Filtered Water On Campus
Water Quality Of Tap And Filtered Water On CampusWater Quality Of Tap And Filtered Water On Campus
Water Quality Of Tap And Filtered Water On CampusLindsey Williams
 
Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...
Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...
Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...SONAL GARG
 
Initial Assessment Microcystin-RTMDW
Initial Assessment Microcystin-RTMDWInitial Assessment Microcystin-RTMDW
Initial Assessment Microcystin-RTMDWRon Zurawell
 
Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...
Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...
Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...larrycotcher
 
The Impact of Ozone as a Secondary Disinfection System
The Impact of Ozone as a Secondary Disinfection SystemThe Impact of Ozone as a Secondary Disinfection System
The Impact of Ozone as a Secondary Disinfection SystemDEL Ozone
 

Similaire à 1 worlwide-water_standars_for_hemodialysis (20)

Calidad del agua para agricultura fao 29-ayers y westcot 1985-oki
Calidad del agua para agricultura fao 29-ayers y westcot 1985-okiCalidad del agua para agricultura fao 29-ayers y westcot 1985-oki
Calidad del agua para agricultura fao 29-ayers y westcot 1985-oki
 
Water copy
Water   copyWater   copy
Water copy
 
Nutdemineralized 1
Nutdemineralized 1Nutdemineralized 1
Nutdemineralized 1
 
Water treatment
Water treatmentWater treatment
Water treatment
 
The And Sustainability Of The Pioneer River Catchment
The And Sustainability Of The Pioneer River CatchmentThe And Sustainability Of The Pioneer River Catchment
The And Sustainability Of The Pioneer River Catchment
 
ARSENIC MITIGATION FOR SAFE GROUNDWATER
ARSENIC MITIGATION FOR SAFE GROUNDWATERARSENIC MITIGATION FOR SAFE GROUNDWATER
ARSENIC MITIGATION FOR SAFE GROUNDWATER
 
Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...
Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...
Kenneyetal.2009.TAR.Benthicmacroinvertebratesasindicatorsofwaterquality_thein...
 
Water quality and sampling
Water quality and samplingWater quality and sampling
Water quality and sampling
 
Long Island's Drinking Water: Threats and Solutions
Long Island's Drinking Water:  Threats and SolutionsLong Island's Drinking Water:  Threats and Solutions
Long Island's Drinking Water: Threats and Solutions
 
Research paper
Research paperResearch paper
Research paper
 
Canadian Se DWQG_Gilron
Canadian Se DWQG_GilronCanadian Se DWQG_Gilron
Canadian Se DWQG_Gilron
 
The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...
The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...
The Effects of Pipe Material and Age on the Formation of Disinfection By – Pr...
 
Water Quality Of Tap And Filtered Water On Campus
Water Quality Of Tap And Filtered Water On CampusWater Quality Of Tap And Filtered Water On Campus
Water Quality Of Tap And Filtered Water On Campus
 
WATER QUALITY.docx
WATER QUALITY.docxWATER QUALITY.docx
WATER QUALITY.docx
 
Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...
Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...
Exploring the Mechanism of Water Disinfection using Antimicrobial Properties ...
 
Initial Assessment Microcystin-RTMDW
Initial Assessment Microcystin-RTMDWInitial Assessment Microcystin-RTMDW
Initial Assessment Microcystin-RTMDW
 
Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...
Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...
Recycled Water: Wastewater Poised to Be a Significant Source of The Nation's ...
 
The Impact of Ozone as a Secondary Disinfection System
The Impact of Ozone as a Secondary Disinfection SystemThe Impact of Ozone as a Secondary Disinfection System
The Impact of Ozone as a Secondary Disinfection System
 
BIS WHO.pptx
BIS WHO.pptxBIS WHO.pptx
BIS WHO.pptx
 
AI_2012_1_Claudi_etal
AI_2012_1_Claudi_etalAI_2012_1_Claudi_etal
AI_2012_1_Claudi_etal
 

Dernier

Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...
Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...
Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...IMARC Group
 
BCE24 | Virtual Brand Ambassadors: Making Brands Personal - John Meulemans
BCE24 | Virtual Brand Ambassadors: Making Brands Personal - John MeulemansBCE24 | Virtual Brand Ambassadors: Making Brands Personal - John Meulemans
BCE24 | Virtual Brand Ambassadors: Making Brands Personal - John MeulemansBBPMedia1
 
Michael Vidyakin: Introduction to PMO (UA)
Michael Vidyakin: Introduction to PMO (UA)Michael Vidyakin: Introduction to PMO (UA)
Michael Vidyakin: Introduction to PMO (UA)Lviv Startup Club
 
Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024Borderless Access
 
Fabric RFID Wristbands in Ireland for Events and Festivals
Fabric RFID Wristbands in Ireland for Events and FestivalsFabric RFID Wristbands in Ireland for Events and Festivals
Fabric RFID Wristbands in Ireland for Events and FestivalsWristbands Ireland
 
AMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdf
AMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdfAMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdf
AMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdfJohnCarloValencia4
 
Mihir Menda - Member of Supervisory Board at RMZ
Mihir Menda - Member of Supervisory Board at RMZMihir Menda - Member of Supervisory Board at RMZ
Mihir Menda - Member of Supervisory Board at RMZKanakChauhan5
 
Talent Management research intelligence_13 paradigm shifts_20 March 2024.pdf
Talent Management research intelligence_13 paradigm shifts_20 March 2024.pdfTalent Management research intelligence_13 paradigm shifts_20 March 2024.pdf
Talent Management research intelligence_13 paradigm shifts_20 March 2024.pdfCharles Cotter, PhD
 
HELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptx
HELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptxHELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptx
HELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptxHelene Heckrotte
 
Ethical stalking by Mark Williams. UpliftLive 2024
Ethical stalking by Mark Williams. UpliftLive 2024Ethical stalking by Mark Williams. UpliftLive 2024
Ethical stalking by Mark Williams. UpliftLive 2024Winbusinessin
 
IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...
IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...
IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...AustraliaChapterIIBA
 
A flour, rice and Suji company in Jhang.
A flour, rice and Suji company in Jhang.A flour, rice and Suji company in Jhang.
A flour, rice and Suji company in Jhang.mcshagufta46
 
NASA CoCEI Scaling Strategy - November 2023
NASA CoCEI Scaling Strategy - November 2023NASA CoCEI Scaling Strategy - November 2023
NASA CoCEI Scaling Strategy - November 2023Steve Rader
 
Plano de marketing- inglês em formato ppt
Plano de marketing- inglês  em formato pptPlano de marketing- inglês  em formato ppt
Plano de marketing- inglês em formato pptElizangelaSoaresdaCo
 
Entrepreneurship & organisations: influences and organizations
Entrepreneurship & organisations: influences and organizationsEntrepreneurship & organisations: influences and organizations
Entrepreneurship & organisations: influences and organizationsP&CO
 
Project Brief & Information Architecture Report
Project Brief & Information Architecture ReportProject Brief & Information Architecture Report
Project Brief & Information Architecture Reportamberjiles31
 
Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024Borderless Access
 
The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...
The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...
The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...Brian Solis
 
Live-Streaming in the Music Industry Webinar
Live-Streaming in the Music Industry WebinarLive-Streaming in the Music Industry Webinar
Live-Streaming in the Music Industry WebinarNathanielSchmuck
 
Q2 2024 APCO Geopolitical Radar - The Global Operating Environment for Business
Q2 2024 APCO Geopolitical Radar - The Global Operating Environment for BusinessQ2 2024 APCO Geopolitical Radar - The Global Operating Environment for Business
Q2 2024 APCO Geopolitical Radar - The Global Operating Environment for BusinessAPCO
 

Dernier (20)

Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...
Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...
Boat Trailers Market PPT: Growth, Outlook, Demand, Keyplayer Analysis and Opp...
 
BCE24 | Virtual Brand Ambassadors: Making Brands Personal - John Meulemans
BCE24 | Virtual Brand Ambassadors: Making Brands Personal - John MeulemansBCE24 | Virtual Brand Ambassadors: Making Brands Personal - John Meulemans
BCE24 | Virtual Brand Ambassadors: Making Brands Personal - John Meulemans
 
Michael Vidyakin: Introduction to PMO (UA)
Michael Vidyakin: Introduction to PMO (UA)Michael Vidyakin: Introduction to PMO (UA)
Michael Vidyakin: Introduction to PMO (UA)
 
Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024
 
Fabric RFID Wristbands in Ireland for Events and Festivals
Fabric RFID Wristbands in Ireland for Events and FestivalsFabric RFID Wristbands in Ireland for Events and Festivals
Fabric RFID Wristbands in Ireland for Events and Festivals
 
AMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdf
AMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdfAMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdf
AMAZON SELLER VIRTUAL ASSISTANT PRODUCT RESEARCH .pdf
 
Mihir Menda - Member of Supervisory Board at RMZ
Mihir Menda - Member of Supervisory Board at RMZMihir Menda - Member of Supervisory Board at RMZ
Mihir Menda - Member of Supervisory Board at RMZ
 
Talent Management research intelligence_13 paradigm shifts_20 March 2024.pdf
Talent Management research intelligence_13 paradigm shifts_20 March 2024.pdfTalent Management research intelligence_13 paradigm shifts_20 March 2024.pdf
Talent Management research intelligence_13 paradigm shifts_20 March 2024.pdf
 
HELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptx
HELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptxHELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptx
HELENE HECKROTTE'S PROFESSIONAL PORTFOLIO.pptx
 
Ethical stalking by Mark Williams. UpliftLive 2024
Ethical stalking by Mark Williams. UpliftLive 2024Ethical stalking by Mark Williams. UpliftLive 2024
Ethical stalking by Mark Williams. UpliftLive 2024
 
IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...
IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...
IIBA® Melbourne - Navigating Business Analysis - Excellence for Career Growth...
 
A flour, rice and Suji company in Jhang.
A flour, rice and Suji company in Jhang.A flour, rice and Suji company in Jhang.
A flour, rice and Suji company in Jhang.
 
NASA CoCEI Scaling Strategy - November 2023
NASA CoCEI Scaling Strategy - November 2023NASA CoCEI Scaling Strategy - November 2023
NASA CoCEI Scaling Strategy - November 2023
 
Plano de marketing- inglês em formato ppt
Plano de marketing- inglês  em formato pptPlano de marketing- inglês  em formato ppt
Plano de marketing- inglês em formato ppt
 
Entrepreneurship & organisations: influences and organizations
Entrepreneurship & organisations: influences and organizationsEntrepreneurship & organisations: influences and organizations
Entrepreneurship & organisations: influences and organizations
 
Project Brief & Information Architecture Report
Project Brief & Information Architecture ReportProject Brief & Information Architecture Report
Project Brief & Information Architecture Report
 
Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024Borderless Access - Global B2B Panel book-unlock 2024
Borderless Access - Global B2B Panel book-unlock 2024
 
The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...
The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...
The End of Business as Usual: Rewire the Way You Work to Succeed in the Consu...
 
Live-Streaming in the Music Industry Webinar
Live-Streaming in the Music Industry WebinarLive-Streaming in the Music Industry Webinar
Live-Streaming in the Music Industry Webinar
 
Q2 2024 APCO Geopolitical Radar - The Global Operating Environment for Business
Q2 2024 APCO Geopolitical Radar - The Global Operating Environment for BusinessQ2 2024 APCO Geopolitical Radar - The Global Operating Environment for Business
Q2 2024 APCO Geopolitical Radar - The Global Operating Environment for Business
 

1 worlwide-water_standars_for_hemodialysis

  • 1. Hemodialysis International 2007; 11:S18–S25 Worldwide water standards for hemodialysis Richard A. WARD Department of Medicine, University of Louisville, Louisville, Kentucky, U.S.A. Abstract Contaminants commonly found in tap water are toxic to hemodialysis patients. To prevent patient injury from these contaminants, standards for the quality of water used to prepare dialysate have been developed. These standards are in general agreement concerning maximum allowable levels of inorganic chemical contaminants known to have adverse consequences for dialysis patients. There is less agreement about inorganic chemical contaminants that may be toxic, and most standards omit any requirements for organic chemical contaminants. There are considerable differences be- tween standards regarding the maximum allowable levels of microbiological contaminants, as well as the methods to be used for measuring them. Harmonization of existing standards may improve patient protection by promoting demonstrated best practices. Harmonization will require innovation and compromise to produce a standard that is widely applicable, provides patients with the neces- sary safeguards, and whose requirements can be routinely achieved within the constraints imposed by local reimbursement practices. Key words: Hemodialysis, water, standards, harmonization INTRODUCTION patients developed symptoms of hypercalcemia.3 Recog- nizing that these problems were related to high levels When hemodialysis was first introduced as a treatment of calcium in the municipal water, nephrologists began for end-stage renal failure in the 1960s, dialysate was treating the municipal water with a softener before it was formulated by adding various salts, and often glucose, to used to prepare dialysate.2,3 tap water. Once the more pressing technical challenges of By the mid-1970s, aluminum, chloramines, copper, dialysis, such as blood access, were addressed and pa- and fluoride had been identified as being definitely or tients began to survive for longer times and in greater probably toxic to hemodialysis patients.1 For aluminum numbers, it became apparent that dialysate prepared from and chloramines, this toxicity was evident at concentra- tap water could contain substances that were harmful to tions commonly found in municipal water supplies. In hemodialysis patients or that caused problems with he- addition, the incidence of pyrogenic reactions during modialysis machines.1 As these substances were identi- hemodialysis was observed to correlate with the level of fied, individual nephrologists began to change their bacteria in the dialysate.4 Thus, it was clear that the water practices. For example, in areas where municipal water used to prepare dialysate needed purification to ensure supplies contained high levels of calcium and magnesium low levels of these contaminants. This realization was the (hard water), the fluid pathways of dialysis machines start of the development of fluid quality standards for became fouled with carbonate precipitates2 and some hemodialysis, a process that continues to the present day. The purpose of this paper is to review the evolution of Correspondence to: R. A. Ward, PhD, Kidney Disease quality standards for water used in hemodialysis applica- Program, University of Louisville, 615 S. Preston Street, tions and discuss some of the issues that may influence Louisville, KY 40202-1718, U.S.A. the development of these standards at the beginning of E-mail: richard.ward@louisville.edu the 21 century. S18 r 2007 The Authors. Journal compilation r 2007 International Society for Hemodialysis
  • 2. Worldwide water standards for hemodialysis In the beginning . . . Protection Agency’s National Interim Primary Drinking Water Standard published in 1975, which set maximum The idea of a quality standard for water used in hemo- contaminant levels for substances that had been deter- dialysis appears to have been considered first in the mined to be hazardous to the health of the general popu- United States in the late 1960s, when the Association lation. Because hemodialysis patients have a much greater for the Advancement of Medical Instrumentation (AAMI) exposure to water than a person with normal renal func- and the American Society for Artificial Internal Organs tion, because the gradient for transfer from dialysate to (ASAIO) began a collaborative effort to write a standard blood may be maintained throughout dialysis because of for hemodialysis machines. A tentative draft of that stand- protein binding, and because hemodialysis patients lack ard was published for comment in 1970. This initial draft renal excretion, the maximum allowable levels for these suggested that the quality of water used to prepare dial- substances was set at one-tenth of the EPA maximum al- ysate should meet the requirements of the United States lowable level for drinking water or the no-transfer level. Pharmacopoeia for purified water, with an additional (The no-transfer level for a solute is defined as that dial- limit on heavy metals (o0.01 mg/L) and a minimum re- ysate concentration at which there will be no net transfer sistivity of 1 MO cm at 25 1C if deionized water was used. of the solute across the dialyzer membrane, given a nor- This draft underwent numerous revisions over the next 9 mal plasma concentration of the solute.) The maximum years, and it was not until 1979 that the AAMI Renal allowable level of bacteria in the water was based on the Disease and Detoxification Committee finally reached observation that the incidence of pyrogenic reactions was agreement on its content. About the same time, Prakash significantly increased if the level of bacteria in the dial- Keshaviah at the Minneapolis Medical Research Founda- ysate exceeded 2000 CFU/mL.4 Experience suggested that tion, under contract to the United States Food and Drug dialysis machines in use at the time the standard was Administration, was preparing a report identifying the being developed could amplify the bacterial burden in the risks and hazards associated with conventional hemodi- water by a factor of 10. Therefore, the maximum allow- alysis systems. Because of the potential overlap between able level of bacteria in the water was set at 200 CFU/mL. these 2 endeavors, the AAMI Renal Disease and Detoxi- fication Committee decided to wait for Keshaviah’s report Current water quality standards and before finalizing their standard. Keshaviah’s report ap- peared in June 19805 and many of its recommendations recommendations were incorporated into the first AAMI standard for he- In the years since the AAMI standard was first published, modialysis systems, which was finally published in May many other countries have established standards or rec- 1982.6 A parallel effort took place in Canada, with the ommendations for the quality of water used in hemo- Canadian Standards Association publishing a draft stand- dialysis. These standards and recommendations have ard (CSA Standard Z364.2) in 1978. been prepared by standards organizations (e.g., Canadi- The AAMI standard established maximum levels of a an Standards Association,7 American National Standards range of chemical contaminants and bacteria in the water Institute/AAMI,8 International Organization for Standard- used to prepare dialysate (Tables 1 and 2), as well as a ization [ISO]9), pharmacopoeias (e.g., Europe,10 United maximum level of bacteria in the final dialysate. The States11), and professional associations (e.g., European water quality requirements of the Canadian standard Renal Association-European Dialysis and Transplant were substantially the same as those in the AAMI stand- Association [ERA-EDTA],12 Japanese Society for Dialysis ard. The substances covered by these standards could be Therapy13). While there is general agreement concerning divided into 4 groups (Tables 1 and 2): substances with the maximum allowable levels of inorganic chemicals documented toxicity in hemodialysis patients; substances with documented toxicity in hemodialysis patients (alu- normally included in dialysate; other trace elements; and minum, chloramines, copper, fluoride, lead, nitrate, sul- microbiological contaminants. For substances with doc- fate, and zinc), there are some exceptions. For example, umented toxicity in hemodialysis patients, the maximum the current edition of the European Pharmacopoeia does levels were set at values less than the lowest level at which not explicitly specify maximum allowable levels for cop- toxicity had been documented. For substances normally per or chloramines. In the latter case, the European Phar- included in dialysate, the maximum levels were set so that macopoeia does specify a maximum allowable level for the water would not significantly affect the final dialysate total available chlorine and provides a test method that composition. The other trace elements included in the will detect both free chlorine and chloramines.10 As the standard were based on the United States Environmental maximum allowable level for total available chlorine is set Hemodialysis International 2007; 11:S18–S25 S19
  • 3. Ward Table 1 Recommended maximum concentrations of chemical contaminants in water used for hemodialysis Canadian Standards United States European Contaminant (mg/L) AAMI8 Association7 Pharmacopoeia11 Pharmacopoeia10 Substances with documented toxicity in hemodialysis patients Aluminum 0.01 0.01 0.01 0.01 Chloramines 0.10 0.10 0.10 — Free chlorine 0.50 — 0.50 — Total available chlorine — — — 0.1 Copper 0.10 0.10 0.10 — Fluoride 0.20 0.20 0.20 0.20 Lead 0.005 0.005 0.005 — Nitrate (as N) 2.00 2.00 2.00 2.00 Sulfate 100 100 100 50 Zinc 0.10 0.10 0.10 0.10 Substances normally included in dialysate Calcium 2 2 2 2 Magnesium 4 4 4 2 Potassium 8 8 8 2 Sodium 70 70 70 50 Other substances Ammonia — — — 0.2 Antimony 0.006 0.006 0.006 — Arsenic 0.005 0.005 0.005 — Barium 0.10 0.10 0.10 — Beryllium 0.0004 0.0004 0.0004 — Cadmium 0.001 0.001 0.001 — Chromium 0.014 0.014 0.014 — Chloride — — — 50 Mercury 0.0002 0.0002 0.0002 0.001 Selenium 0.09 0.09 0.09 — Silver 0.005 0.005 0.005 — Thallium 0.002 0.002 0.002 — Total heavy metals — — — 0.10 Total organic carbon — 0.500 — — AAMI =Association for the Advancement of Medical Instrumentation. at the same value as other standards set for chloramines, modialysis water standard because there were no data there is effectively no difference in quality requirements. documenting their toxicity in hemodialysis patients. The In addition, there are some differences in how the various extent to which standards for water used in dialysis ap- standards treat heavy metals and substances normally in- plications should continue to be influenced by drinking cluded in dialysate (magnesium, potassium, and sodium; water standards remains an open question as discussed Table 1). Some standards (Canada, United States, ISO) later in this review. Overall, and with the exception of the specify limits for individual heavy metals, while others omission of copper from the European Pharmacopoeia, (European Pharmacopoeia) set a limit for heavy metals as there is no compelling evidence of adverse clinical con- a group. Also, the range of heavy metals included in the sequences arising from the minor differences between standards has evolved over time. Three additional heavy standards in the allowable levels of inorganic chemical metals (antimony, beryllium, and thallium) were added to contaminants. the AAMI standard in 2001 by virtue of their inclusion in Of note, none of the existing standards and recom- the United States drinking water standard. The AAMI Re- mendations includes limits for specific organic chemical nal Disease and Detoxification Committee expressed contaminants. The rationale for this omission is that or- some hesitation about adding these elements to their he- ganic chemicals with specific toxicity to hemodialysis S20 Hemodialysis International 2007; 11:S18–S25
  • 4. Worldwide water standards for hemodialysis Table 2 Recommended maximum levels of microbiological able levels of microbiological contaminants in water used contaminants in water used for hemodialysis for hemodialysis. These differences involve not only the levels of microbiological contaminants (Table 2) but also Bacteria Endotoxin the methods used to measure them (Table 3). The original (CFU/mL) (EU/mL) AAMI standard set a maximum allowable level for bac- AAMI8 200 2 teria of 200 CFU/mL. Subsequently, other stand- Canadian Standards Association7 100 2 ards7,10,11,16 and recommended practices12,17 set the United States Pharmacopoeia11 100 2 level at 100 CFU/mL, which is not substantially different European Pharmacopoeia10 100 0.25 from 200 CFU/mL, given the variability inherent in using Swedish Pharmacopoeia16 100 0.25 plate counts to determine bacterial levels. As discussed ERA-EDTA12a 100 0.25 Japanese Society for — 0.25 later, however, there may actually be significant differen- Dialysis Therapy13 ces in the allowable level of bacteria, depending on what Italian Society of Nephrology17a 100 0.25 culturing methods are specified. The original AAMI a standard did not set a limit for endotoxin because, at Both the ERA-EDTA and the Italian Society of Nephrology recom- that time, no convenient test for endotoxin was available. mend that all dialysis facilities aim for ultrapure dialysate. AAMI =Association for the Advancement of Medical Instrumenta- In 2001, the AAMI standard was revised to include a tion; ERA-EDTA = European Renal Association-European Dialysis maximum allowable level of endotoxin of 2 EU/mL meas- and Transplant Association. ured using the Limulus amebocyte lysate assay. This change took place after a lengthy debate about whether or not there was sufficient clinical evidence to support inclusion of a maximum allowable level of endotoxin. This cautious patients have not been identified and that carbon adsorp- approach is in marked contrast to the position taken in tion and reverse osmosis should remove most organic Europe and Japan, where a considerably lower maximum compounds. That hemodialysis patients may be at risk allowable level of endotoxin (0.25 EU/mL) was intro- from organic compounds is evidenced, however, by re- duced during the 1990s. Indeed, many authorities advo- cent reports from Italy describing contamination of water cate even lower maximum allowable levels for bacteria by organo-halogenated compounds that were not re- and endotoxin (0.1 CFU/mL and 0.03 EU/mL, respective- moved by standard hemodialysis water treatment prac- ly), although so far these levels remain recommendations, tices,14,15 including the use of activated carbon and rather than requirements. Fluids meeting this more rig- reverse osmosis. The Canadian standard7 does include a orous quality standard are referred to as ‘‘ultrapure.’’18 maximum allowable level for total organic carbon Low levels of endotoxin and other bacterial products in (0.5 mg/L); however, it is not clear that meeting this re- dialysate have been implicated in the low-level chronic quirement would protect against toxic levels of many or- inflammation observed in hemodialysis patients. Use of ganic compounds. ultrapure fluids is believed to ameliorate this inflamma- In contrast to chemical contaminants, there are signif- tion and delay or reduce the severity of long-term com- icant differences in the recommended maximum allow- plications of hemodialysis therapy, such as malnutrition, Table 3 Recommended method for determining bacterial levels in water used for hemodialysis Incubation Incubation Culture medium temperature ( 1C) time (hr) AAMI8 TSA 35 to 37 48 Canadian Standards Association7 TSA, SMA, R2A 35 48 United States Pharmacopoeia11 TSA 30 to 35 48 European Pharmacopoeia10 R2A 30 to 35 120 Swedish Pharmacopoeia16 TGEA 22 120 ERA-EDTA12a R2A 20 to 22 144 Italian Society of Nephrology17a TGEA, R2A 20 to 23 120 to 144 a Both the ERA-EDTA and the Italian Society of Nephrology recommend that all dialysis facilities aim for ultrapure dialysate. AAMI =Advancement of Medical Instrumentation; ERA-EDTA = European Renal Association-European Dialysis and Transplant Association; R2A = Reasoner’s 2A; SMA = standard methods agar; TGEA = tryptone glucose extract agar; TSA = tryptic soy agar. Hemodialysis International 2007; 11:S18–S25 S21
  • 5. Ward b2-microglobulin amyloidosis, resistance to erythropoie- best practices and a standard that is enforced as a regu- tin, and loss of residual renal function.19 lation. Both models, as well as various hybrid versions, In addition to differences in the maximum allowable are currently in use around the world. For example, in levels of endotoxin, there are important differences the United States, compliance with the AAMI standard between standards in the methods recommended for for water quality is required if a facility is to receive pay- measuring bacterial contamination. The original AAMI ment for hemodialysis services from the United States standard allowed the use of tryptic soy agar (TSA), stand- Government’s Medicare program and compliance is ard methods agar (SMA), or blood agar, with enumeration monitored by periodic inspections of dialysis facilities. of colonies after incubation for 48 hr at 37 1C.6 It was In contrast, compliance with standards is either not soon realized that the nutrient-rich environment pro- required or not enforced by inspection in many other vided by blood agar was not appropriate for culturing jurisdictions. A quality standard enforced as a regulation organisms adapted to a purified water environment and must be capable of being met routinely by a typical dia- the use of blood agar was eliminated as an option in sub- lysis facility at a cost consistent with local reimbursement sequent versions of the standard.8 Later studies also practices. In contrast, a standard intended as a guide to showed that the combination of TSA and incubation at best practices may recommend a level of quality that can 37 1C for 48 hr was not optimal for recovery of water- be met only by commitment of additional resources at the borne organisms. Use of nutrient-poor media, such as discretion of an individual dialysis facility that believes Reasoner’s 2A and tryptone glucose extract agar, and that level of quality will be of benefit to its patients. A longer incubation times at room temperature resulted in harmonized standard should be capable of serving both colony counts that were often an order of magnitude functions. higher than those obtained with TSA incubated for 48 hr It may be possible for a standard to serve both a regu- at 37 1C.18 These more stringent culturing conditions latory and an advisory role by including 2 grades of water have been adopted in whole, or in part, by several or- quality in the standard. The first grade would establish ganizations issuing standards or recommendations for the maximum allowable concentrations of contaminants quality of water used for hemodialysis (Table 3). based on definitive evidence that higher concentrations of a contaminant would be harmful to patients. The sec- ond grade may recommend a lower concentration of a Where do we go from here? contaminant where there was a suggestion that the lower Some in the dialysis community believe that the time is concentration may be associated with improved patient right to harmonize existing quality standards for water outcomes. This approach has been used by the ERA- used in hemodialysis applications. It is suggested that a EDTA and the Italian Society of Nephrology, which have harmonized standard would help disseminate demon- adopted the European Pharmacopoeia quality standard strated best practices in countries with well-established for maximum allowable levels of contaminants, but rec- hemodialysis programs, thereby decreasing the likelihood ommend the use of ultrapure fluids.12,17 of both acute and chronic adverse events related to water As is evident from Tables 1 and 2, there are some dif- quality. It could also serve as a guideline for countries ferences in the range of contaminants included in the where chronic hemodialysis is still in its infancy. Finally, a various standards and recommendations, as well as in the harmonized standard may contribute to better technology maximum allowable level of individual contaminants. A for water purification and distribution by establishing harmonized standard would require a resolution of these a consistent set of expectations for equipment manufac- differences. turers. Current efforts to revise and expand the ISO’s As mentioned previously, some current standards do standards related to fluids used for hemodialysis may act not explicitly include chloramines even though their tox- as an impetus to harmonization. Before harmonization icity in hemodialysis patients has been documented re- can occur, however, 2 important questions must be an- peatedly over 30 years.20,21 It has been argued that there swered: Is harmonization desirable and feasible; and, how is no need to include chloramines in a standard for a should the maximum allowable levels of contaminants be region where chloramines are not used to disinfect determined? municipal water supplies. However, patient injury has The desirability and feasibility of harmonizing water occurred in many parts of the world when municipal quality standards depend, in part, on how such standards water providers began using chloramines with little or no are used. There is a significant difference between a prior notice to dialysis facilities. For this reason, it seems standard used to provide guidance on demonstrated reasonable that a harmonized standard should include all S22 Hemodialysis International 2007; 11:S18–S25
  • 6. Worldwide water standards for hemodialysis contaminants with documented toxicity in hemodialysis about the strength of the evidence for strontium toxicity patients. The benefits of avoiding toxicity almost certainly and the concentration at which it occurs. outweigh the cost of routine monitoring for these con- Microbiological contaminants present a particular taminants. problem in trying to reach consensus on maximum al- Whether or not to include contaminants that have no lowable levels of contaminants. As described earlier, cur- documented toxicity in hemodialysis patients is a more rent standards differ significantly in the maximum difficult question. Heavy metals were included in the ori- allowable level of endotoxin. Further, even though there ginal AAMI standard because their levels in drinking does not appear to be a large difference in plate count water were regulated as a matter of public health and values, in reality, there may be significant differences in because they were thought to pose a greater risk to he- the maximum allowable level of bacteria because of dif- modialysis patients because of the mechanism of expos- ferences in recommended culturing methods. In general, ure and the lack of renal excretion. Other standards have European and Japanese standards set a lower maximum chosen to deal with heavy metals collectively by estab- allowable level for endotoxin than the United States lishing a maximum allowable level for them as a group. standard (Table 2). In addition, there is widespread sup- Neither approach is entirely satisfactory. Including a sub- port for the use of ultrapure fluids in both Europe and stance in the standard because it is included in drinking Japan, based on a growing literature showing improve- water regulations implies that any substance added to the ments in outcomes such as nutrition and anemia correc- drinking water regulations should be added to the he- tion when ultrapure dialysate is used. Some in the United modialysis water standard. This situation has arisen in the States dialysis community argue, however, that the evi- United States, leading to the addition of antimony, beryl- dence used to support lower levels of endotoxin and, in lium, and thallium to the hemodialysis water standard in particular, ultrapure dialysate is not convincing. They cite 2001 even though there was no evidence that they posed the absence of controlled clinical trials comparing out- a particular risk to hemodialysis patients. This open- comes obtained with lower levels of endotoxin, including ended, non-evidence-based approach only serves to in- ultrapure dialysate, with those obtained with dialysate crease the cost and complexity of monitoring water for meeting the current United States quality standards. They hemodialysis without any apparent benefit to patients. also worry about the cost and feasibility of routinely Combining the heavy metals into a single group is attrac- meeting a more stringent quality standard in a regulated tive as it has the potential to reduce the cost of routine environment where reimbursement is tightly controlled. water analyses. However, treating heavy metals as a With regard to water, these arguments may be somewhat group implies that the maximum allowable level for moot. It should be remembered that patients are treated the group should not exceed the maximum allowable with dialysate, not water, and it is the microbiological level for the most toxic member of that group. Cur- quality of the dialysate that is important. In general, ultra- rently, maximum allowable levels for 10 heavy metals pure dialysate is prepared by point-of-use filtration of the included in the standards that list each heavy metal dialysate immediately before it enters the dialyzer. Clearly, individually are below the 0.1 mg/L level set in the Eu- higher quality water reduces the burden on the final ul- ropean Pharmacopoeia for total heavy metals. At this trafilter; however, currently available point-of-use ultra- point, it remains unclear how best to deal with trace con- filtration systems should be capable of producing taminants, with no clearly defined toxicity in the setting ultrapure dialysate from concentrates and water that rou- of hemodialysis. tinely meet any of the quality standards listed in Table 2. However this issue is resolved, an effective standard Thus, the cost aspect of ultrapure dialysate shifts from should incorporate a mechanism for promptly adding a debate about whether or not the quality of the water new substance that may, in the future, be shown to be used to prepare the dialysate should be ultrapure to toxic to hemodialysis patients. Although candidate toxins whether or not to install point-of-use ultrafilters for the are rare, examples have appeared in recent years. Lead, final dialysate. which was included in the original AAMI standard be- All of these arguments are predicated on the assump- cause its levels were regulated in drinking water, was re- tion that endotoxin levels are an adequate measure of ported recently to be toxic in hemodialysis patients,22 water quality. Endotoxin testing reveals nothing about the although the level at which toxicity occurs is not well levels of other microbiological contaminants, including defined. Strontium contamination of water used to pre- yeasts, fungi, peptidoglycans, and fragments of bacterial pare dialysate has been implicated in bone disease in he- DNA, all of which have been identified in water used for modialysis patients,23,24 although there is still debate hemodialysis.25–27 Hemodialysis International 2007; 11:S18–S25 S23
  • 7. Ward SUMMARY 7 Canadian Standards Association. Water Treatment Equip- ment and Water Quality Requirements for Hemodialysis, Hemodialysis patients are at risk from contaminants in Z364.2.2-03. Toronto, ON: Canadian Standards Associa- the water used to prepare dialysate. To mitigate this risk, tion; 2003. various organizations have developed standards and rec- 8 Association for the Advancement of Medical Instru- ommendations for water quality over the past 25 years. mentation. Water Treatment Equipment for Hemodialysis There is general agreement concerning maximum allow- Applications, ANSI/AAMI RD62:2001. Arlington, VA: As- able levels of inorganic chemical contaminants known to sociation for the Advancement of Medical Instrumenta- have adverse consequences for dialysis patients. There is tion; 2001. less uniformity when it comes to inorganic chemical con- 9 International Organization for Standardization. Water for taminants that may have toxicity and an almost complete Haemodialysis and Related Therapies, ISO 13959:2002(E). silence in the area of organic chemical contaminants. Geneva: International Organization for Standardization; Further, there are considerable differences between the 2002. 10 European Pharmacopoeia Commission. European various standards and recommendations regarding the Pharmacopoiea, 5th ed. Monograph 2005:1167, Haemodi- maximum allowable levels of microbiological contamin- alysis Solution, Concentrated, Water for Diluting. Stras- ants and the methods to be used for measuring these bourg: European Pharmacopoeia Commission; 2005. contaminants. Harmonization of the various standards 11 United States Pharmacopoiea. h1230iWater for health and recommended practices may help protect patients by applications, water for hemodialysis. First supplement to promoting demonstrated best practices and providing a USP 28-NF 23, 2005. road map for those countries where large-scale hemodi- 12 European Renal Association-European Dialysis and alysis is still in its infancy. Achieving harmonization will Transplant Association. European best practice guidelines require innovation and compromise to produce a stand- for haemodialysis (part I), section IV: Dialysis fluid purity. ard that is widely applicable, provides patients with the Nephrol Dial Transplant. 2002; 17(Suppl 7):45–62. necessary safeguards, and whose requirements can be 13 Morii K, Morii H, Asano Y, Naitoh H, Takesawa S. Stand- routinely achieved within the constraints imposed by ard for safety of dialysis fluid. J Jpn Soc Dial Ther. 1998; local reimbursement practices. 31:1107–1109. 14 Formica M, Vallero A, Forneris G, et al. Organo-haloge- nated contamination of a dialysis water treatment plant. G Ital Nefrol. 2002; 19:479–482. Manuscript received August 2006; revised September 15 Poli D, Pavone L, Tansinda P, et al. Organic contam- 2006. ination in dialysis water: Trichloroethylene as a model compound. Nephrol Dial Transplant. 2006; 21:1618– 1625. REFERENCES ¨ ¨ 16 Swedish Pharmacopoeia. Lakemedelsstandard for Finland 1 Ward RA. Water processing for hemodialysis. Part I: A och Sverige (Preparation and Handling of Solutions for historical perspective. Semin Dial. 1997; 10:26–31. ¨ Haemodialysis). Lakemedelsverket: Svenska Far- 2 Ivanovich P, Marr TA, Gothberg LA, Steury RE, Drake RF . ´ ´ makopekommitten; 1997. A compact hydraulic proportioning system for hemodi- 17 Italian Society of Nephrology. Guidelines on water and alysis. Trans Am Soc Artif Int Organs. 1966; 12:357–359. solutions for dialysis. G Ital Nefrol. 2005; 22:246–273. 3 Freeman RM, Lawton RL, Chamberlain MA. Hard-water 18 Ledebo I, Nystrand R. Defining the microbiological qual- syndrome. N Engl J Med. 1967; 276:1113–1118. ity of dialysis fluid. Artif Organs. 1999; 23:37–43. 4 Favero MS, Petersen NJ, Boyer KM, Carson LA, Bond 19 Ward RA. Ultrapure dialysate. Semin Dial. 2004; 17: WW. Microbial contamination of renal dialysis systems 489–497. and associated health risks. Trans Am Soc Artif Int Organs. 20 Ward DM. Chloramine removal from water used in he- 1974; 20:175–183. modialysis. Adv Renal Replac Ther. 1996; 3:337–347. 5 Keshaviah P, Luehmann D, Shapiro F Comty CM. Inves- , 21 Ward RA. Dialysis water as a determinant of the ad- tigation of the Risks and Hazards Associated with Hemodi- equacy of dialysis. Semin Nephrol. 2005; 25:102–111. alysis Devices. Silver Spring, MD: U.S. Department of 22 Kathuria P, Nair B, Schram D, Medlock R. Outbreak of Health, Education, and Welfare, Food and Drug Admin- lead poisoning in a hemodialysis unit (abstract). J Am Soc istration; 1980. Nephrol. 2004; 15:617A. 6 Association for the Advancement of Medical Instrumen- 23 Schrooten I, Elseviers MM, Lamberts LV, De Broe ME, tation. Hemodialysis Systems, ANSI/AAMI RD5-1981. Ar- D’Haese PC. Increased serum strontium levels in dialysis lington, VA: Association for the Advancement of Medical patients: An epidemiological survey. Kidney Int. 1999; Instrumentation; 1982. 56:1886–1892. S24 Hemodialysis International 2007; 11:S18–S25
  • 8. Worldwide water standards for hemodialysis 24 D’Haese PC, Schrooten I, Goodman WG, et al. Increased 26 Tsuchida K, Takemoto Y, Yamagami S, et al. Detection of bone strontium levels in hemodialysis patients with os- peptidoglycan and endotoxin in dialysate, using silk- teomalacia. Kidney Int. 2000; 57:1107–1114. worm larvae plasma and limulus amebocyte lysate meth- 25 Klein E, Pass T, Harding GB, Wright R, Million C. Mi- ods. Nephron. 1997; 75:438–443. crobial and endotoxin contamination in water and dial- 27 Schindler R, Beck W, Deppisch R, et al. Short bacterial ysate in the central United States. Artif Organs. 1990; DNA fragments: Detection in dialysate and induction of 14:85–94. cytokines. J Am Soc Nephrol. 2004; 15:3207–3214. Hemodialysis International 2007; 11:S18–S25 S25