HDF AWAK and Green dialysis

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Hemodiafiltration

• Avula Srinivas
• Aswini Hospitals
• Guntur

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Online hemodiafiltration

• What is online Hemodiafiltration (OL-HDF )
• Clinical benefits of HDF
• Clearance
• Cardiovasculaar stability
• Anemia
• Does OL HDF improve survival
• Association between survival and convective
  volume
• Safety and cost
• Conclusions

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Hemodialysis

• Maintenance hemodialysis (HD) prevents immediate
  death from uremia,
• Fewer expected remaining life years, compared
  with the general population or patient
  populations with cancer, diabetes, or
  cardiovascular disease
• The persistence of a residual uremic syndrome,
• Incomplete correction of inorganic ion
  disturbance,
• Intradialytic hypotension (IDH)-induced
  myocardial stress, and repeated injury of the
  compromised cardiovascular system by aggravation
  of systemic low-grade inflammation associated
  with ESRD using bio-incompatible dialysis
  compounds (membrane chemistry)
• Microbiological purity of dialysis fluid

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Hemodialysis

• Improving urea clearance did not improve survival
• So the concept of middle molecules
• High flux Dialysis

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HIGH-PERFORMANCE EXTRACORPOREAL THERAPIES FOR
END-STAGE RENAL DISEASE

• 1-High-efficiency hemodialysis
• 2-High-flux hemodialysis
• 3-Hemofiltration(intermittent)
• 4-Hemodiafiltration( intermittent)
• Online Hemodiafiltration

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Hemodiafiltration

• The European Dialysis Working Group defined
  hemodiafiltration (HDF) as a single RRT that
  combines diffusive and convective solute removal
  by ultrafiltration of 20 or more of the blood
  volume processed through a high-flux dialyzer and
  maintenance of fluid balance by sterile,
  nonpyrogenic replacement-fluid infusion directly
  into the patients blood.

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PORE SIZE
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PORE SIZE
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Purity of water

• Microbiological safety during HDF is a matter of
  concern because large volumes of online-produced
  fluid are directly infused into the patient

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Water

• Ultrapure water
• (virtually sterile and nonpyrogenic water)
• Current AAMI recommendations lt200(CFU)/mL of
  bacteria
• lt2.0 endotoxin units (EU)/mL of endotoxin
• Ultrapure dialysis solutionlt0.1 CFU/mL and lt0.03
  EU/mL endotoxin
• The ultrafilters are replaced periodically to
  prevent supersaturation and release of endotoxins.

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post-dilution hemodiafiltration
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Vascular access

• Patients treated with HF/HDF require an access
  capable of delivering an extracorporeal blood
  flow of at least 350 mL per minute, and
  preferably higher.

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Membrane

• Flux
• Measure of ultrafiltration capacity
• Low and high flux are based on the
  ultrafiltration coefficient (Kuf)
• Low flux Kuf lt10 mL/h/mm Hg
• High flux Kuf gt20 mL/h/mm Hg
• Permeability
• Measure of the clearance of the middle molecular
  weight molecule (eg, ß2-microglobulin)
• General correlation between flux and permeability
• Low permeability ß 2-microglobulin clearance lt10
  mL/min
• High permeability ß 2-microglobulin clearance
  gt20 mL/min
• Efficiency
• Measure of urea clearance
• Low and high efficiency are based on the urea KoA
  value
• Low efficiency KoA lt500 mL/min
• High efficiency KoA gt600 mL/min

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Membrane

• The membrane should have a high hydraulic
  permeability (KUF 50 mL / hour / mm Hg), high
  solute permeability (K0A urea gt600) and
  beta2-microglobulin clearance gt60 mL/ min), and
  large surface of exchange (1.50-2.10 m2).

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Typical prescriptions and substitution fluid
infusion rates

• The conventional HDF/HF treatment schedule is
  based on three dialysis sessions per week of 4
  hours (12 hours per week).

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Online hemodiafiltration

• What is online Hemodiafiltration (OL-HDF )
• Clinical benefits of HDF
• Clearance
• Cardiovasculaar stability
• Anemia
• Does OL HDF improve survival
• Association between survival and convective
  volume
• Safety and cost
• Conclusions

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Solute clearance diffusive/convective
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Clearance

• Phosphate and urea no advantage
• Middle molecule Increases middle molecule
  clearance does not translate to better outcomes

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Online hemodiafiltration

• What is online Hemodiafiltration (OL-HDF )
• Clinical benefits of HDF
• Clearance
• Cardiovasculaar stability
• Anemia
• Does OL HDF improve survival
• Association between survival and convective
  volume
• Safety and cost
• Conclusions

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Meta-analysis ..CV and all cause mortality
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Reasons for cardiovascular stability

• Na conc higher due to replacement fluid
• Cooling effect

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Online hemodiafiltration

• What is online Hemodiafiltration (OL-HDF )
• Clinical benefits of HDF
• Clearance
• Cardiovasculaar stability
• Anemia
• Does OL HDF improve survival
• Association between survival and convective
  volume
• Safety and cost
• Conclusions

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All cause mortality high risk factors
May be due to better biocompatibility / ultrapure
dialysate
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Online hemodiafiltration

• What is online Hemodiafiltration (OL-HDF )
• Clinical benefits of HDF
• Clearance
• Cardiovasculaar stability
• Anemia
• Does OL HDF improve survival
• Association between survival and convective
  volume
• Safety and cost
• Conclusions

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All cause mortality high risk factors
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Mortality data in observational studies
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Conflicting Results ?
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Online hemodiafiltration

• What is online Hemodiafiltration (OL-HDF )
• Clinical benefits of HDF
• Clearance
• Cardiovasculaar stability
• Anemia
• Does OL HDF improve survival
• Association between survival and convective
  volume
• Safety and cost
• Conclusions

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Convective volume

• Pre-dilution gt 50L / week
• Post-Dilution gt20L/ weel
• Also depends on body weight

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HDF in Children

• Furthermore, published data on HDF in children
  are very limited. In this group of patients, a
  totally different endpoint, growth acceleration,
  could be of great relevance.

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What does the present data implicate

• There is a trend towards with higher gt20/L
  convective volumes
• better Cardiovascular stability with Ol-HDF
• Better anaemia correction
• Less mortality

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What about

• Cost
• Safety esp microbiological

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Is the data convincing

• No
• In the era of evidence based medicine there is
  need for further studies

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CONVINCE

• Multicenter randomized controlled study
• Hf HD / OL-HDF
• Ongoing in Europe
• Results expected in 2020
• May provide some answers

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Other uses of HDF

• Poisonings ..
• Myeloma/ light chains removal

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• Finally, it is possible that specific subgroups
  of patients would especially benefit from HDF

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Next

• We now go from conventional methods of dialysis
  to innovative portable dialysis

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Innovations in Wearable and Implantable
Artificial Kidneys
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Disadvantages of RRT at present

• Transplantation Availability of organs and
  immunosuppression related complications
• Diaysis
• Costly
• Limited mobility/Travel
• Heavy equipment
• Medical waste/ water consumption
• Dependent on Power supply

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Drawbacks of Dialysis now
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Portable Dialysis Technologies

• Dialysate Regeneration
• AWAK (Automated wearable artificial Kidney)
• WAK ( Wearable Artificial Kidney )
• IAK ( Implantable Artificial Kidney )

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PD comparison
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AWAKautomated implantable artificial kidney

• 2 litres dialysate with 500ml tidal exchanges
• Each exchange 7.5 mins
• 8 exchanges every hour/96L per day
• Spent dialysate passes though sorbent filter
• Sorbent cartridge can be used for 7 hours

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Study

• 20 male patients for 4 to 20 hours
• Double lumen/ two single lumen PD catheters
• Average urea clearance 31.4 ml/min

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AWAK ( Peritoneal Dialysis )
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AWAK
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The automated wearable artificial kidney (AWAK)
system tidal exchanges are done with 500 mL of
spent dialysate being drained from the peritoneal
cavity to the storage module, cleaned in the
sorbent cartridge, replenished with electrolytes
in the enrichment module, and returned to the
peritoneal cavity. Excess fluid is drained in the
ultrafiltration bag to be disposed of with the
disposable module shown here. Redrawn from an
image supplied by AWAK Technologies, Ltd.
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wearable
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Portable Dialysis Technologies

• Dialysate Regeneration
• AWAK (Automated wearable artificial Kidney)
• WAK ( Wearable Artificial Kidney )
• IAK ( Implantable Artificial Kidney )

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Modified hemodialysis WAK
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WAK
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Schematic of wearable artificial kidney (WAK)
system. Blood from the catheter is anticoagulated
using the heparin pump. A shuttle pump pumps
blood through the dialyzer. The blood is
reconstituted with electrolytes and returns to
the patient. The dialysate goes through the
dialyzer and the spent dialysate goes to the
dialysate regenerating system to be used again
with any excess dialysate discarded into the
ultrafiltration bag. The system has alarms in
place for leaks or bubbles. Image is 2007
Elsevier Ltd and is reproduced from Davenport et
al8 with permission of the copyright holder.
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wAK
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Clinical trials
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Victor Gura, MD, inventor of the Wearable
Artificial Kidney 2019

• So far the WAK has been in development for 18
  years
• The first clinical trial of the WAK ran from
  October 2014 and April 2015 and included seven
  patients.
• I think we're about two years from funding the
  next round to be in the market."

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Future
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Wak

• Average urea cl was 22.7 ml/min
• CO2 bubbles created problems with flow
• Clotting of dialyzer and dislodgement of needles
  created problems hence catheters needed
• Long-term access and coagulation needs to be
  addressed

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Portable Dialysis Technologies

• Dialysate Regeneration
• AWAK (Automated wearable artificial Kidney)
• WAK ( Wearable Artificial Kidney )
• IAK ( Implantable Artificial Kidney )

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David Humes 1999University of Michigan
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Pioneers
Shuvo Roy PhD ( Bioengineering and Therapeutic
sciences ) University of California San Francisco
William H Fissell IV MD ( Nephrology and
Hypertension ) Vanderbilt University medical
center Nashville TN
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Illustrative
The implantable artificial kidney (IAK) is
implanted into the vasculature with blood pumped
using the patients blood pressure into the
HemoCartridge with membranes that mimic the
slit-shaped pores of podocytes and then through
the Bio- Cartridge that contains living tubular
cells, thus mimicking the glomerulus-tubule
arrangement of the kidney.
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Portable
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The catridges
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Illustrative IAK
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IAK..silicon chips
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IAK.biofilter with human tubular cells
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Challenges ..

• Initial surgery and presumably later surgeries
  for replacement
• Thrombus free operation for years
• Mammalian cells undergo slow erosion culture
  Stress
• Govt. regulations and reimbursement yet unknown

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Advantages

• No Power/ water supply
• Better quality of life with better clearances
• Continuous therapy with less complications
  intradialytic
• Do not depend on organ donation
• No immunosuppression or rejection
• No need for replacement cartridges

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IAK

• While the request for additional evidence was not
  anticipated, it is a measure of the revolutionary
  nature of our project that there is no precedent
  for safety reviews of similar technology and
  materials, wrote the organization. In that
  light, it is understandable that the research
  ethics boards are requesting additional data to
  document the safety of the bioartificial kidney.

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Comparison
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Which one wins the race ?

• All complementary to one another
• Probably will hit the market in another 5 years (
  purely speculative) as barriers to market entry
  are formidable for any new device
• Technical challenges
• Regulatory and reimbursement challenges

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WAK/IAK have low water/power consumption

• Green Dialysis

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Green Dialysis

• The need of the hour

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Aim

• Environmentally sustainable
• Minimal or no harm to ecosystems
• Leave a better place for future generations
• Dialysis being power hungry and water hungry with
  lot of plastic use so how can we make it
  environmentally friendly

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Attempts to address these issuesin Dialysis

• It seeks ways to save water.
• It offers options for alternative power.
• It considers options in waste management.
• It even dreams of building re-design.

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Water

• Current HD water use is careless, not careful.
• Aproximately 500 L / 4 hour session
• Can we reuse ?

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Water reuse

• To provide water for hospital laundries
• To create steam for sterilization
• As grey water in toilet facilities
• In sanitation systems/janitor stations in wards
• In low pressure boilers
• For watering of onsite gardens
• To provide water to nearby services, businesses,
  or parks many would be grateful for access to
  reliable, low-cost (or free) water source.
• Encourage the children of staff and/or patients
  to open a weekend, low-cost, car wash for the
  community using RO reject water some money for
  the kids pockets, and a reuse option for the
  reject water

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Hemodialysis (HD) is a power-hungry process

• Standard power saving measures
• Natural lighting/ LED
• Solar

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Counter current exchange of heat

• Normally, the heated water flows directly into
  the drain after the dialysis, unused. In order to
  save on energy resources and costs, B. Braun
  Avitum AG and Viessmann Deutschland GmbH
  collaboratively developed a product in order to
  increase the energy efficiency of the process
  the energy of the outflowing dialysate is
  supplied to the cold, incoming water through
  central thermal recovery. This is accomplished by
  the installation of two highly efficient heat
  exchangers with separate water circuits. The
  installation can be monitored by remote access.
  The system is particularly intended for
  installation in new construction and renovation
  projects in renal care centers. Retrofitting into
  existing systems is also possible.

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Plastic and infectious waste

• Each dialysis treatment generates a mean 2.5 kg
  of infectious waste/patient,
• Polyvinyl chloride (PVC) recycling
• PVC is the most commonly used polymer in medical
  products and forms a large part of hospital
  general waste sent to landfill at high cost.
• it is made from vinyl chloride, a potent human
  toxin
• its disposal to landfill can cause phthalates to
  leech into soil and ground water
• its manufacture and incineration releases
  dioxins, that can enter the human food chain and
  cause a wide spectrum of adverse effects in
  humans.
• But, programs do now exist for recycling of PVC
  in hospitals, allowing the conversion of PVC into
  useful products hosing for fire extinguishers,
  gardens and industry safety mats for children
  and workplaces.

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Dialyser

• Reuse

• Single use

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General waste

• Cardboard can be re-cycled
• dialysis soft plastics aside
• lack of coordinated waste disposal in HD seems to
  remain a barrier too high yet, the potential
  benefits are huge.

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Designing of unit
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Fuel consumption

• Transport
• Most dialysis patients receive facility based HD.
• This mandates thrice weekly travel to and from
  their local healthcare facility. It is therefore
  not surprising that travel contributes
  significantly to the carbon footprint of
  dialysis.
• While the ability to reduce transport-related
  emissions depends on geographical location, all
  should consider
• Encouraging staff and patients in active
  transport (cycling, walking and public transport)
• Providing secure bike facilities, shower and
  changing areas
• Investigating one-way transport options if
  patients could walk to dialysis but cannot return
  home the same way due to post-dialysis fatigue.

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Manufacturing and procurement

• Similarly, an Australian study estimated that
  procurement accounted for 61.6 of the carbon
  footprint of a satellite dialysis unit, in
  contrast to 18.6 for electricity usage, 8.8 for
  patient and staff travel and 7.6 for water
  usage.
• Because of this, meaningful efforts to reduce the
  renal sector carbon footprint must address
  procurement.

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How do we do ??

• Appoint an Eco-Leader
• Going Green needs commitment, focus and
  leadership.
• Set up eco-idea boxes or boards where both
  patients and staff can post their ideas.
• Send round an e-newsletter/email, seeking ideas
  and suggestions for being greener.
• Involve the patients as well as the dialysis
  staff.
• Consider offering prizes theatre tickets, a
  dinner out for the most innovative suggestion
  of the month.
• Consider appointing a staff member as water
  monitor, as power protector, or as waste
  manager.
• Learn what others are doing join the UK
  Sustainable Healthcare group where much of this
  work has already been put into practice

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Conclusions

• Water conservation and reuse
• Natural lighting, wind/solar energy and
  countercurrent heat exchanges
• Plastic .. Avoid and reuse intelligently
• Fuel saver by reducing transport costs
• Actively involve and evolve new ideas
• And leave behind a better legacy

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Thank you