DIALYSIS FLUID QUALITY: AN IMPORTANT PART OF THE DIALYSIS PRESCRIPTION

Presented by Dr. Richard Ward

A Webber Training Teleclass, March 11, 2004

DIALYSIS FLUID QUALITY:

AN IMPORTANT PART OF THE DIALYSIS OVERVIEW
PRESCRIPTION
• WHAT IS THE ROLE OF DIALYSIS FLUID (DIALYSATE) IN
Dr. Richard A. Ward HEMODIALYSIS?
University of Louisville
• WHY IS THE QUALITY OF THE DIALYSIS FLUID
IMPORTANT?

• WHAT ADVERSE OUTCOMES MAY BE RELATED TO

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[email protected]
• HOW CAN SAFE LEVELS OF THESE CONTAMINANTS BE
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ASSURED?

HEMODIALYSIS HEMODIALYSIS

ƒ REPLACES THE EXCRETORY BLOOD

FUNCTIONS OF THE KIDNEY
ANTICOAGULATION
9 REGULATES WATER WASTE METABOLITES DIALYZER
∆C
BALANCE (UREA, CREATININE, URIC ACID)
ELECTROLYTES
9 REGULATES ELECTROLYTE (POTASSIUM, PHOSPHATE)

BALANCE ∆P
WATER
BLOOD PUMP
9 ELIMINATES WASTE DIALYSIS
PRODUCTS OF METABOLISM
∆C FLUID
HCO3-
BLOOD ACCESS
ƒ DOES NOT REPLACE SEMIPERMEABLE
MEMBRANE
ENDOCRINE AND METABOLIC DIALYSIS
FUNCTIONS OF THE KIDNEY FLUID BLOOD
TUBING

DIALYSIS FLUID PREPARATION

PREPARATION OF DIALYSIS FLUID
FIXED
DIALYSIS
MACHINE
DIALYZER ACID HCO3-
DIALYSIS (1 PART) (1.83 PARTS)
FLUID DIALYSATE
HEATER
WATER
(34 PARTS) CT

WATER DYNAMIC ACID HCO3-

DRAIN DIALYSATE
WATER
ACID CONCENTRATE HEATER
CA CT
BICARBONATE CONCENTRATE

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DIALYSIS FLUID QUALITY: AN IMPORTANT PART OF THE DIALYSIS PRESCRIPTION
Presented by Dr. Richard Ward
A Webber Training Teleclass, March 11, 2004

360 l/wk
TOXIC WATER CONTAMINANTS
CONTAMINANT SOURCE ADVERSE EVENT

ALUMINUM MUNICIPAL WATER ENCEPHALOPATHY, BONE DISEASE,

ANEMIA
14 l/wk CHLORAMINES MUNICIPAL WATER HEMOLYSIS

FLUORIDE MUNICIPAL WATER FATAL ARRHYTHMIA, BONE DISEASE (?)

CYANOTOXIN SOURCE WATER LIVER FAILURE

NITRATES SOURCE WATER ANEMIA

GI TRACT
NON-SELECTIVE
ENDOTOXIN DIALYSIS UNIT PYROGENIC REACTIONS, CHRONIC
MEMBRANE
INFLAMMATION
COPPER DIALYSIS UNIT HEMOLYSIS, NAUSEA, VOMITING

ZINC DIALYSIS UNIT HEMOLYSIS, NAUSEA, VOMITING

URINARY
CALCIUM, SOURCE WATER, NAUSEA, VOMITING
EXCRETION MAGNESIUM MUNICIPAL WATER

ANEMIA OR APPARENT ERYTHROPOIETIN

RESISTANCE
• CHLORAMINES
– OXIDIZES HEMOGLOBIN TO METHEMAGLOBIN
• 8 CASES OF FATAL DIALYSIS ENCEPHALOPATHY OBSERVED IN
– INHIBITS ANTIOXIDANT PATHWAYS
22 MONTHS (38% OF ALL PATIENTS).
• COINCIDED WITH ADDITION OF ALUMINUM SULFATE AND SODIUM • COPPER
ALUMINATE TO THE CITY WATER RESULTING IN DIALYSIS FLUID – INHIBITS ANTIOXIDANT PATHWAYS
ALUMINUM CONCENTRATIONS OF 200 - 1000 µg/L (AVERAGE 675 – DECREASES RBC DEFORMABILITY
µg/L), AND AN ESTIMATED LOAD OF ALUMINUM WITH EACH
DIALYSIS TREATMENT OF 3 - 16 mg. • ZINC
• THE OUTBREAK ENDED AFTER INSTALLATION OF DEIONIZER • ALUMINUM
THAT REDUCED DIALYSIS FLUID ALUMINUM TO < 1 µg/L. – DECREASES HEMOGLOBIN SYNTHESIS
– INTERFERES WITH IRON METABOLISM

AAMI WATER QUALITY STANDARDS - RD62:2001

CHLORAMINE-INDUCED HEMOLYSIS
SUBSTANCES IN DIALYSATE SUBSTANCES TOXIC IN DIALYSIS
40 CALCIUM 2 ALUMINUM 0.01
MAGNESIUM 4 CHLORAMINES 0.10
SODIUM 70 FREE CHLORINE 0.5
RBC HALF-LIFE (days)

30 POTASSIUM 8 COPPER 0.10

TOXIC SUBSTANCES (SDWA) FLUORIDE 0.20
ANTIMONY 0.006 NITRATE (as N) 2.0
20 ARSENIC 0.005 SULFATE 100
[CHLORAMINE] BERYLLIUM 0.0004 ZINC 0.10
BARIUM 0.1
= 3 mg/L
CADMIUM 0.001 MICROBIOLOGICAL CONTAMINANTS
10
CHROMIUM 0.014 BACTERIA 200
LEAD 0.005 ACTION LEVEL 50
MERCURY 0.0002 ENDOTOXIN 2
0 SELENIUM 0.09 ACTION LEVEL 1
TAP WATER DISTILLED WATER SILVER 0.005
THALIUM 0.002
WATER SOURCE FOR DIALYSATE
CHEMICAL CONCENTRATIONS IN mg/L, BACTERIA CFU/ml, ENDOTOXIN EU/ml
Kjellstrand C et al. Nephron 13:427, 1974

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DIALYSIS FLUID QUALITY: AN IMPORTANT PART OF THE DIALYSIS PRESCRIPTION
Presented by Dr. Richard Ward
A Webber Training Teleclass, March 11, 2004

WATER TREATMENT SYSTEM PURIFICATION PROCESSES

• REQUIRED FOR ALL DIALYSIS FACILITIES PROCESS CONTAMINANT

• MUST PRODUCE WATER OF APPROPRIATE QUALITY CARBON ADSORPTION CHLORAMINES, ORGANICS
FROM THE WORST CASE FEED WATER
SOFTENER CALCIUM
• MUST MEET THE PEAK DEMAND FOR WATER (SOME
EXCESS CAPACITY IS DESIRABLE)
REVERSE OSMOSIS IONIC CONTAMINANTS,
• SHOULD BE DESIGNED FOR EASE OF MAINTENANCE BACTERIA, ENDOTOXIN

DEIONIZATION IONIC CONTAMINANTS

ULTRAFILTRATION BACTERIA, ENDOTOXIN

PRIMARY
PRE-TREATMENT PURIFICATION

PRE-TREATMENT
BLENDING
VALVE REVERSE
OSMOSIS
• PROTECTS THE PRIMARY PURIFICATION PROCESS
DEPTH CARBON SOFTENER 5µm FILTER – DEPTH FILTER REMOVES LARGER PARTICULATES (> 15 µm)
FILTER
THAT CAN FOUL DOWN-STREAM PROCESSES
INLET – SOFTENER REMOVES CALCIUM THAT CAN FOUL REVERSE
WATER OSMOSIS MEMBRANES
DISTRIBUTION – CARBON REMOVES CHLORINE THAT CAN DEGRADE REVERSE
OSMOSIS MEMBRANES
DIALYSIS STORAGE
STATIONS TANK • ESTABLISHES OPTIMUM OPERATING CONDITIONS FOR
PRIMARY PURIFICATION PROCESS

• PROTECTS PATIENTS BY REMOVING CHLORAMINE

ULTRAFILTER

PRIMARY PURIFICATION
REMOVAL OF CHLORAMINES REVERSE OSMOSIS versus ION EXCHANGE
• CARBON ADSORPTION WITH GRANULAR ACTIVATED
CARBON OR CATALYTIC CARBON IS GENERALLY THE MOST • REVERSE OSMOSIS
EFFECTIVE MEANS OF REMOVING CHLORAMINES – REMOVES A WIDE RANGE OF IONIC AND NON-IONIC CONTAMINANTS (DOES
NOT REMOVE CHLORAMINES)
• CARBON ADSORPTION MAY NOT BE EFFECTIVE UNDER – PROVIDES A BARRIER AGAINST MICROBIOLOGICAL CONTAMINANTS
RARE CIRCUMSTANCES: – GENERALLY REQUIRES PRE-TREATMENT OF FEED WATER (CALCIUM,
– HIGH LEVELS OF N-CHLORAMINES CHLORINE, COLLOIDS)
– SIGNIFICANT CAPITAL COST, BUT LOW OPERATING COST
– USE OF ORTHOPHOSPHATE TO REDUCE LEAD AND COPPER
LEVELS IN THE MUNICPAL WATER • ION EXCHANGE
– HIGH pH IN THE MUNICIPAL WATER – DOES NOT REMOVE NON-IONIC CONTAMINANTS (MAY LIMIT Al REMOVAL)
– HAS A FINITE CAPACITY
UNDER THESE CIRCUMSTANCES, CARBON ADSORPTION
– PROMOTES BACTERIAL PROLIFERATION
MAY NEED TO BE SUPPLEMENTED; FOR EXAMPLE, BY
– RISK OF ACUTE FLUORIDE TOXICITY IF ALLOWED TO EXHAUST
INJECTION OF METABISULPHITE
– LOW CAPITAL COST, BUT SIGNIFICANT OPERATING COST

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DIALYSIS FLUID QUALITY: AN IMPORTANT PART OF THE DIALYSIS PRESCRIPTION
Presented by Dr. Richard Ward
A Webber Training Teleclass, March 11, 2004

INLET REVERSE
WATER OSMOSIS

DEPTH CARBON SOFTENER 5µm FILTER

FILTER
WHAT ABOUT
DISTRIBUTION LOOP DIALYSIS FLUID
QUALITY?
DIALYSIS STORAGE
STATIONS TANK

ULTRAFILTER

DIALYSIS FLUID QUALITY

DIALYSIS FLUID
AAMI RD52 - DIALYSATE FOR HEMODIALYSIS
DEFINITIONS OF MICROBIOLOGICAL QUALITY
PROPOSED LIMITS FOR CHEMICAL CONTAMINANTS
• SAME AS FOR WATER (RD62:2001) Bacteria (cfu/ml) Endotoxin (EU/ml)
AAMI Recommended 200 2
PROPOSED LIMITS FOR MICROBIOLOGICAL CONTAMINANTS Practice (Proposed)
• BACTERIA: 200 CFU/ml ERA-EDTA Best Practice 100 0.25
ACTION LEVEL: 50 CFU/ml Guidelines
Ultrapure 0.1 <0.03
• ENDOTOXIN: 2 EU/ml
ACTION LEVEL: 1 EU/ml -6
Sterile 10 <0.03

INTRADIALYTIC PYROGENIC REACTIONS

SEPTICEMIA AND PYROGENIC REACTIONS
30
PYROGENIC REACTION RATE (%)

• BACTERIA
 DO NOT CROSS DIALYZER MEMBRANES
 MAY INFECT BLOOD COMPARTMENT DURING 20
PROCESSING OF DIALYZER FOR REUSE
 CAN CAUSE SEPSIS CHARACTERIZED BY WATER-
BORNE ORGANISMS

• ENDOTOXIN 10

 FRAGMENTS MAY CROSS DIALYZER MEMBRANES

 MAY CONTAMINATE BLOOD COMPARTMENT DURING
PROCESSING OF DIALYZER FOR REUSE 0
 CAUSE PYROGENIC REACTIONS CHARACTERIZED BY 1 - 100 100 - 10000 > 10000
SHAKING CHILLS, FEVER AND HYPOTENSION DIALYSATE BACTERIA (CFU/ml)

Favero MS et al. Trans Am Soc Artif Int Organs 20:175-183, 1974

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DIALYSIS FLUID QUALITY: AN IMPORTANT PART OF THE DIALYSIS PRESCRIPTION
Presented by Dr. Richard Ward
A Webber Training Teleclass, March 11, 2004

INFLUENCE OF DIALYSIS PRACTICES ON

DIALYZER REUSE: OUTBREAKS OF SEPTICEMIA
PYROGENIC REACTIONS
AND PYROGENIC REACTIONS
No
Yes
*
NUMBER OF CENTERS (%)

30
INCORRECT GERMICIDE CONCENTRATION 5/10

*
20
* INAPPROPRIATE GERMICIDE 2/10

USE OF TAP WATER TO CLEAN OR RINSE DIALYZERS 3/10

10
USE OF MULTIPLE GERMICIDES 1/10

0 USE OF WATER NOT MEETING AAMI STANDARDS 10/10

DIALYZER REUSE HIGH-FLUX BICARBONATE

Tokars JI et al. ASAIO J 40:1020-1031, 1994 Arduino MJ et al. Dial Transplant 22:652-656, 1993

RISK OF DEVELOPING DIALYSIS-ASSOCIATED

CHRONIC INFLAMMATION
AMYLOIDOSIS WITH CONTAMINATED DIALYSIS FLUID
• CYTOKINE-INDUCING SUBSTANCES (ENDOTOXIN
FRAGMENTS, PEPTIDOGLYCANS, MURAMYL ODDS RATIO (95% CI)
DIPEPTIDES, EXOTOXINS)
β2-MICROGLOBULIN AMYLOIDOSIS 3.308 (1.45 – 6.35) p = 0.031
 CROSS LOW- AND HIGH-FLUX MEMBRANES
BONE CYSTS 1.85 (1.00 – 3.42) p = 0.047
 STIMULATE MONONUCLEAR CELL CYTOKINE PRODUCTION
 ARE ASSOCIATED WITH INCREASED LEVELS OF ACUTE CARPAL TUNNEL SYNDROME 2.86 (1.35 – 6.07) p = 0.006
PHASE PROTEINS (C-REACTIVE PROTEIN)
 PRODUCE A MICROINFLAMMATORY STATE THAT MAY PLAY A ARTHROPATHY 9.04 (2.06 – 39.6) p = 0.004
ROLE IN β2-MICROGLOBULIN AMYLOIDOISIS, N = 89 CONTAMINATED DIALYSIS FLUID: 550 CFU/ml
ATHEROSCLEROSIS, AND MALNUTRITION 10 YEAR FOLLOW-UP STANDARD DIALYSIS FLUID: 65 CFU/ml

Schiffl H et al. Nephrol Dial Transplant 15:840-845, 2000

POTENTIAL ADVANTAGES OF WATER AND DIALYSIS

FLUID OF HIGH MICROBIOLOGICAL PURITY

• LESS INFLAMMATORY STIMULUS

• REDUCED INCIDENCE OF β2-
MICROGLOBULIN AMYLOID DISEASE
• IMPROVED RESPONSIVENESS TO
ERYTHROPOIETIN
• IMPROVED NUTRITIONAL STATUS
• BETTER PRESERVATION OF RESIDUAL
RENAL FUNCTION
Tubing from a dialysis machine with > 106 CFU/ml
P. aeruginosa, Enterobacter cloacae and Candida parapsilosis
Carr J. Hospital Infections Program, CDCP

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DIALYSIS FLUID QUALITY: AN IMPORTANT PART OF THE DIALYSIS PRESCRIPTION
Presented by Dr. Richard Ward
A Webber Training Teleclass, March 11, 2004

BIOMASS FROM DIALYSIS MACHINE TUBING

TOTAL
CFU/cm2 STRATEGIES FOR BACTERIAL CONTROL
BACTERIA/cm2

TUBING FROM

WATER PATH 23 1.4 x 105 • SYSTEM DESIGN

BICARBONATE PATH 17 1.54 x 105 • SYSTEM OPERATION
DIALYSIS FLUID
12 3.2 x 10 5 • DISINFECTION
PATH

DIALYSIS FLUID 0 0

N=3

Adapted from Man N-K et al. Artif Organs 22:596-600, 1998

DESIGN TO LIMIT BACTERIAL PROLIFERATION

DISINFECTION
• USE A DISTRIBUTION LOOP
• AVOID STAGNANT FLOW • DISINFECTION SCHEDULES SHOULD BE DESIGNED TO PREVENT,
 NO DEAD ENDS, PRESSURIZING TANKS, OR MULTIPLE BRANCHES
NOT ELIMINATE, CONTAMINATION WITH BACTERIA AND BIOFILM.
 SIZE PIPES TO MAINTAIN VELOCITY > 3 ft/sec

• INCLUDE BACTERIAL CONTROL DEVICES

• DISINFECTION SHOULD INCLUDE THE WATER STORAGE AND
DISTRIBUTION SYSTEM, CONCENTRATE PREPARATION AND
 ULTRAFILTERS
 ON-LINE HOT WATER DISINFECTION DISTRIBUTION SYSTEM, AND THE PROPORTIONING SYSTEM.

• IF A STORAGE TANK IS USED • MONITORING WITH CULTURES AND ENDOTOXIN LEVELS IS

 MINIMUM SIZE NEEDED TO ENSURE TURN-OVER OF WATER INTENDED TO VERIFY THE ADEQUACY OF DISINFECTION, NOT
 TIGHT-FITTING LID WITH A HYDROPHOBIC 0.2 µm FILTER AIR VENT INDICATE WHEN DISINFECTION IS NEEDED.
 CONICAL BOTTOM WITH DRAIN AT LOWEST POINT
 ADEQUATE DISINFECTION MECHANISM

NO MAN’S LINE
MONITORING FOR COMPLIANCE WITH AAMI
STANDARDS
CULTURING CONDITIONS
TECHNIQUE MEMBRANE FILTER, SPREAD PLATE
MEDIUM TRYPTIC SOY AGAR OR EQUIVALENT
TEMPERATURE 35 - 37°C
TIME 48 hours
ENDOTOXIN MEASUREMENT
TECHNIQUE LIMULUS AMEBOCYTE LYSATE ASSAY

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DIALYSIS FLUID QUALITY: AN IMPORTANT PART OF THE DIALYSIS PRESCRIPTION
Presented by Dr. Richard Ward
A Webber Training Teleclass, March 11, 2004

ALTERNATIVES TO SPREAD-PLATE CULTURES EFFECT OF CULTURE CONDITIONS ON COLONY

• CALIBRATED LOOP
COUNT IN DIALYSATE
– STANDARD TECHNIQUE IN CLINICAL LABORATORIES
– SAMPLE VOLUME IS TOO SMALL FOR REQUIRED SENSITIVITY 4
– SPECIFICALLY PROHIBITED FOR DIALYSIS APPLICATIONS

BACTERIA (log CFU/ml)

• PADDLES 3
– CONVENIENT FOR ON-SITE TESTING
– REQUIRE A MAGNIFIER AND LIGHT-SOURCE FOR ACCURATE
ENUMERATION OF COLONIES 2

– MAY GIVE AN APPARENT FALSE NEGATIVE WITH HEAVILY

CONTAMINATED SAMPLES
1
• MEMBRANE FILTRATION
– VERY SENSITIVE
0
– REQUIRES FILTRATION SYSTEM AND LARGE SAMPLE VOLUMES BLOOD AGAR TSA TGEA TGEA
37°C 37°C 37°C 20°C

Ledebo I, Nystrand R. Artif Organs 23:37-43, 1999

SUMMARY
Continuing Education
Certificate
• HEMODIALYSIS PATIENTS ARE HIGHLY SENSITIVE TO
CONTAMINANTS IN THE WATER USED FOR DIALYSIS FLUID AND
DIALYZER REPROCESSING

• WATER CONTAMINANTS CAN CAUSE MANY PROBLEMS COMMON To find out how to get a Continuing
IN HEMODIALYSIS PATIENTS, INCLUDING ANEMIA, BONE
DISEASE, AND INTRA-DIALYTIC NAUSEA AND VOMITING Education Certificate for this teleclass
• NO WATER SUPPLY CAN BE CONSIDERED SUITABLE FOR contact . . .
DIALYSIS APPLICATIONS WITHOUT PURIFICATION

• AVOIDING COMPLICATIONS FROM WATER CONTAMINANTS

REQUIRES CONSTANT ATTENTION TO WATER QUALITY
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