1. WATER QUALITY FOR HEMODIALYSIS
Dr. RAMA ENGANTI
MD, DM
CONSULTANT NEPHROLOGIST

2. WATER QUALITY
Water quality refers to the physical, chemical, biological and radiological characteristics of water 
It is a measure of the condition of water relative to the requirements.

3. Weekly Water Exposure

4. WATER SUPPLY
There are 2 sources of municipal water: surface water and ground water
Surface water is generally more contaminated with organisms and microbes, industrial wastes, fertilizers, and sewage.
Ground water is generally lower in organic materials but contains higher inorganic ions such as Fe, Ca, Mg and sulfate

5. DETERMINANTS OF WATER QUALITY
The final quality of treated water for hemodialysis depends on the configuration of the treatment system and the quality of the feed water.
Regional and seasonal variations in feed water should be considered.
The quality and contaminants in feed water should be measured at maximum contamination during the year.

6. TOXIC EFFECTS OF WATER CONTAMINANTS
Possible effects
Aluminum
Dialysis encephalopathy, renal bone disease
Calcium, Magnesium
Hard water syndrome, hypertension, hypotension
Chloramine
Hemolysis, anaemia, methameglobinemia, EPO resistance
Copper
Nausea, headache, liver damage, fatal hemolysis
Zinc
Hemolysis ,anemia, vomiting, fever
Fluoride
Osteomalacia, osteoporosis, pruritus
Lead
Abdominal pain, anemia, peripheral neuropathy
Nitrate
Methemoglobinemia, hypotension, nausea
Sulfate
Nausea, vomiting, metabolic acidosis
Microbial
Pyrexia reactions, chills, fever, shock
Aromatic hydrocarbons
Potential chemical carcinogens

7. GUIDELINES FOR WATER QUALITY
Indian society of nephrology guidelines for hemodialysis units recommends that all HD units should achieve the water quality of AAMI standards.
Should aim to attain European Standards of purity of water.

8. ASSOCIATION OF ADVANCED MEDICAL INSTRUMENTATION (AAMI)
MAXIMUM LEVELS
AAMI 2004
AAMI 2011
ACTION LEVEL
Water
Water Dialysate
Microbial contamination (CFU/ml)
200 50
Endotoxin levels (IU/ml) 2
0.125

9. EUROPEAN PHARMACOPOEIA
CRITERIA
WATER FOR HD
ULTRAPURE WATER
STERILE WATER
BACTERIA CFU/ml
100
0.1
ENDOTOXIN IU/ml
0.25
0.03

10. ULTRAPURE DIALYSIS SOLUTION
Decreases CRP and IL-6
Improves response to EPO
Promotes better nutrition
Reduces plasma levels of ß-2-microglobulin
Slows loss of residual renal function
Lowers cardiovascular morbidity
Susantitaphong P et al. Effect of ultrapure dialysate on markers of inflammation, oxidative stress, nutrition and anemia parameters: a meta-analysis. NDT (2013) 28:

13. WATER TREATMENT Pretreatment Filtration for suspended particles.
Activated carbon filtration
Softener +/- deionizers
Primary water treatment
Reverse Osmosis
Storage facilities
Storage tank with bottom drain, air tight lid, de-aeration valve.
Stainless Steel(316) or Med grade PVC
Distribution of treated water
Continuous, closed loop preferred with minimal bends and no blind ends Stainless Steel(316) or Med grade PVC
Ultrafiltration and endotoxin-retentive filters may be included after the deionizer, immediately after the storage tank, and/or before delivery to the dialysis machine.

14. Schematic diagram example of a water treatment system for hemodialysis

15. MAINTENANCE OF WATER QUALITY
All dialysis units should have a unit specific quality management program for the water treatment plant and the water distribution system . The quality management program should include the following:
Maintenance practices
Structured monitoring program
Documentation & trend analysis
Troubleshooting actions , with clearly delineated lines of responsibility

16. Maintenance of water treatment system
Component
Monitoring Parameter
Maintenance required
Recommended Frequency
Depth Filter
Pressure drop across filter
Backwashing & Rinsing
Twice a week and daily during the monsoon or when water contains extra suspended particles/impurities.
Activated Carbon Filter
Twice a week
Chlorine in product water
Changing of charcoal
If > 0.1 μg/ml.
Softener
Hardness
Regeneration
Failure to achieve 10 fold decrease.
Membrane filters
Change of filter
>25%
Reverse Osmosis membranes
Inlet, Reject and Permeate pressures & flows
Increase in inlet pressure > 25%., or decrease in permeate flow by 25%
Cleaning of membranes offline
Conductivity
Increase by 50% from baseline
Cleaning of membranes offline or Replacement
Deioniser
Conductivity or resistivity
< 1megaohm or > 0.5 microhms/cm
Regeneration with acid and alkali
Storage tank and Pipeline
Bacterial counts
>50% increase over baseline.
Cleaning & Disinfection

17. MAINTENANCE/CLEANING RO MEMBRANES
Done offline and the system shut down during the process.
The flow of reject gradually increases if process is successful.
Membranes backwashed at low pressure using an external pump and flow in the same direction as normal operation. Each membrane is cleaned individually.
2 cleaning solutions are generally required.
a) Sodium tripolyphosphate and Sodium edetate at a pH adjusted to > 10 to remove calcium scales and low level organic foulants.
b) 2% Citric acid (no pH adjustment required) removes calcium carbonate, metal oxides and inorganic colloidal compounds and also provides disinfection.

18. A water wash is recommended between the cleaning solutions.
A final disinfection of the membranes using 1% peracetic acid or 2% formalin (to be treated for at least 6 hours) is recommended.
After a cleaning and disinfection cycle; the first 200 to 250 liters of water or permeate over 1 hour should be discarded.
The pH of the permeate should be confirmed before using.

19. AAMI LISTED MATERIALS FOR DISTRIBUTION SYSTEM
Polyvinylchloride (PVC), Chlorinated polyvinylchloride(CPVC) Poly vinylidene fluoride(PVDF), Cross-linked polyethylene (PEX), Stainless steel (SS), Polypropylene (PP) Polyethylene (PE), Acrylonitrile butadiene styrene (ABS), Polytetrafluorethylene (PTFE). PVC (Type 1, Schedule 40 or 80) and SS /stainless steel (316L) are the two most commonly used in hemodialysis systems

20. DISINFECTANTS FOR DISTRIBUTION SYSTEM
CHEMICAL: Sodium hypochlorite (chlorine bleach)
peracetic acid & formaldehyde,
Hot water/ inline steam and ozone (dissolved in water).
Peracetic acid is listed compatible with all distribution materials.
Incompatibilities exist between material and disinfectant
Sodium hypochlorite with SS and ABS; formaldehyde with ABS; hot water with PVC, CPVC, PE, and ABS;
ozone with PP and ABS.
Incompatibilities can cause leaching or corrosion of the materials, which may pose a risk to the patient.

21. CLEANING & DISINFECTION OF DISTRIBUTION SYSTEM.
Chemical : Storage tank filled with 50 to 100 L of 1% sodium hypochlorite. After a contact time of 30 minutes the solution is circulated in the loop for 20 minutes and drained followed by a complete rinsing with water which is discarded until a negative test with a starch iodide paper or a conductivity equal to that of the feed water is obtained.
When biofilm has formed and is resistant to disinfection, cleaning the system with 2 to 3 percent citric acid before disinfection may help in biofilm removal.

22. MONITORING WATER QUALITY
Three aspects of water/dialysate quality should be achieved.
a. Chemical purity
b. Microbiological purity
c. Endotoxin purity

23. MONITORING WATER QUALITY
Online
Physical parameters: flow rate, pressure and temperature.
Chemical parameters: Conductivity and Ph
conductivity meters(temperature compensated) with visible & audible alarm in the dialysis technician’s station.
Offline : Chemical analysis once in 3 months in independent laboratory having adequate instrumentation for testing
Patients : Clusters of unexplained pyrogenic and hemolytic reactions
Documentation to enable trend analysis

24. CONTAMINANT
METHOD
MAX AAMI mg/L
MAX EP mg/L
ALUMINIUM
ATOMIC ABSORPTION SPECTROMETRY
0.0100
ANTIMONY
AAS
0.0060
ARSENIC
0.0050
BARIUM
0.1000
BERYLLIUM
0.0004
CADMIUM
0.0010
CALCIUM
2 (0.05mm/L) 2
CHROMIUM
0.0140
COPPER
LEAD
MAGNESIUM
4 (0.16mm/L)
2 (0.08mm/L)
MERCURY
0.0002
SELENIUM
0.0900
SILVER
THALLIUM
0.0020
ZINC

25. CONTAMINANT
METHOD
AAMI MAX mg/L
EP MAX mg/L
CHLORAMINE
COLORIMETRY
0.1
CHLORINE
0.5
NITRATE
2.00
SULPAHATE
TURBIDOMETRY
100
CYANIDE
SPECTROPHOTOMETRIC
0.200
FLOURIDE
MOLECULAR PHOTOLUMINESCENCE
SODIUM
FLAME PHOTOMETRY
70(3.0mm/L)
50(2.2mm/L)
POTASSIUM
8(0.02mm/L)
2(0.08mm/L)

26. MANUAL CHLORINE TESTING (COLORIMETER)
This method uses a photometer
Chlorine reacts with diethyl-p-phenylene diamine (DPD) in a buffered solution to produce a pink colour.
Capable, reliable method of detecting dangerously high levels of chlorine and/or chloramine. This test method has an acceptable level of reliability, sensitivity, accuracy and repeatability, and constitutes the lowest acceptable level of testing appropriate for a dialysis unit.

28. SAMPLING PRECAUTIONS
The system should have been operating for at least 20 to 30 minutes before sampling
All sampling points should provide direct access to the water stream to be sampled.
Sampling should not be done from areas of stagnant flow or at the end of a long length of dead-end tubing.
For aseptic technique (for microbiologic quantification), only alcohol can be used, should dry completely before collecting .
Liquid should be allowed to flow for at least 30 seconds before sampling.

29. MICROBIAL TESTING
Pour plate technique Sample (typically 1 mL) is placed in a Petri dish, and 15 to 20 mL of molten medium is added. The sample and medium are mixed carefully by gentle rotation and allowed to set. The plate is inverted and incubated. For 1 mL of sample, the detection limit of this technique is 1 CFU/mL. Membrane filtration Sample filtered through a membrane filter with pore diameter 0.45 mu . Can detect low levels of contamination (usually <1 CFU/mL) Culture media nutrient poor media such as Tryptone Glucose Extract Agar (TGEA) or Reasoner’s Agar 2A, Soy triptone agar Incubation temperature – Samples should be incubated at 20 to 24ºC & 37 C & growth checked after 48hr & 7 days

30. ENDOTOXIN TESTING
LIMULUS AMEBOCYTE LYSATE (LAL) ASSAY. GEL/CLOT TEST Use sample containers, validated for storage of samples for endotoxin determination. Such containers are usually specified by the testing laboratory or the manufacturer of the LAL assay kit.

31. SUMMARY
Product water quality depends on the design of the water treatment system and the quality of the feed water.
Major maintenance tasks are best performed by trained external contractors/manufacturer; day-to-day maintenance by trained dialysis facility staff members.
Routine disinfection of the water distribution system is essential to prevent the formation of bacterial biofilm, as it is difficult to remove, once formed. 
Monitoring is performed in a predetermined schedule, based upon the system performance following installation.

32. SUMMARY Monitoring, maintenance, and servicing should be documented.
For improved patient outcomes, the ultimate goal is to shift to the use of ultrapure fluids as the technology improves .

33. THANK YOU