Volume Management in Hemodialysis A Moving.123

IMuo2hXmffFQ0IhrVKdI6wDqfuJKUdg1tsKAyF7JXOXvQ1kT29V+INqs2RM49V59cdDjUkH6dwrf4S2HemMr8th15tr2fgxsK7f2
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Authors: Simon J. Davies
Title: Volume management in hemodialysis – a moving target
Running title:
Manuscript Type: Perspective

D/g== on 05/21/2023
Manuscript Category: Dialysis
Funders: There was no external financial support for this article
Financial Disclosure: S.J. Davies reports the following: Consultancy: Ellen Medical;
Research Funding: National Institute of Health Research (UK); Kidney Research UK, EU
Horizon 2020; Baxter HealthCare; Honoraria: Baxter HealthCare, Fresenius Medical Care;
Advisory and Leadership Role: International Society of Peritoneal Dialysis (Member, co-chair
PDOPPS Committee); International Society of Nephrology (Kidney Failure Strategy);
President EuroPD, Trustee Kidney Research UK.
Study Group/Organization Name:
Study Group Members’ Names:
Abstract:
Copyright © 2023 by the American Society of Nephrology

Acknowledgments:
The content of this article reflects the personal experience and views of the author(s) and
should not be considered medical advice or recommendation. The content does not reflect the
views or opinions of the American Society of Nephrology (ASN) or Kidney360.
Responsibility for the information and views expressed herein lies entirely with the author(s).
D/g== on 05/21/2023

Kidney360 Publish Ahead of Print
DOI: 10.34067/KID.0000000000000108
Volume management in hemodialysis – a moving target
Simon J. Davies
Professor of Nephrology and Dialysis medicine,

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School of Medicine,
Keele University, UK
Keywords: blood pressure, fatigue, person-centered care, intradialytic

hypotension, bioimpedance, relative blood volume monitoring, lung
ultrasound, left ventricular hypertrophy
Correspondence:
School of Medicine,
David Weatherall Building,
Keele University
ST5 5BG
UK
s.j.davies@keele.ac.uk
This is an open access article distributed under the terms of the Creative Commons
Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Introduction
My first exposure to haemodialysis was in 1976 when, as a first-year medical student I

visited the home of a friend with kidney failure. His bedroom was transformed into a mini
hospital where he made up his own Kiil dialysers, used two independent volumetric pumps
to control the blood flow, which he had learned to balance since the age of 16, and a weigh
bed to monitor his intra-dialytic fluid removal. It left an impression. A lot has changed since
then including the case-mix of people on dialysis, their expectations and priorities,
treatment goals and strategies and technological advances. This brief article will look at how
these have evolved over time and speculate as to how they might continue to develop
(Table 1).
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A changing demographic
Since the early years of dialysis there has, at least in high income countries, been a huge
change in the demographic of the dialysis population, increasingly characterised by older
people with increasing numbers of comorbid conditions. For a treatment that entails
repeated episodes of cardiovascular stress this represents a very real challenge, especially
when it comes to volume management. For example, many of the factors that exacerbate
intradialytic hypotension, the most commonly reported and troublesome dialysis
complication, can be attributed to an ageing and damaged cardiovasular system. 1 Whereas
hypertension was once the main concern of volume control, hypotension is now a
significant risk factor and challenge when fluid needs to be removed. Fatigue, the symptom
that haemodialysis patients would most wish to be rid of,2 is undoubtedly exacerbated by
the increased frailty of this population, as is prolonged post-dialysis recovery time, itself
associated with worse survival.3

Changing expectations
Alongside these demographic changes have come different expectations. This is in part
because of a change in the balance of importance between quality and quantity of life that
naturally happens with aging, but more fundamentally, a change in the nature of the
relationship between healthcare professionals and the people they treat. We have moved
from a disease-centred model of care through patient-centred and increasingly a person-
centred care model, although full realisation of this is still some way off. 4 This has direct
implications for volume management which hinges around the setting of the post-dialysis
target weight. By any definition, the setting of the target weight is a complex decision that
needs to take many factors into account that influence both fluid balance and fluid
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distribution, (see Table 2), but without ‘co-production’ of an agreed target with the patient -
that may well require some negotiation, it cannot be claimed that person-centred care is
happening.
An evolving strategy
For far too long dialysis prescription was dominated by small solute clearance. This was in
part driven by a desire to minimise treatment times but also a rather simplistic approach to
fluid management, which went along the lines of ‘remove as much fluid as you can,
preferably so that blood pressure is controlled by volume management alone’. The focus on
maximising rapid solute clearance meant that volume management was often ignored, or
worse, by forcing fluid removal into shorter and shorter dialysis treatments it became
positively detrimental. While this might seem to belong to the distant past, a relatively
recent survey of dialysis practices in the UK indicated that this was a common approach in
half of the responding centres.5 The realisation that high ultrafiltration rates, with their risk
of intra-dialytic cardiac stress, hypotension and organ damage, and that hypovolaemia
induced inter-dialytic thirst are all consequences of this approach has led to the recognition
that more sophisticated strategies are needed. These concerns prompted the proposal for a
‘volume first’ approach when prescribing dialysis, with consensus that volume status should
be prioritised in clinical management, ultrafiltration rates limited, intradialytic sodium

loading avoided, dialysate sodium concentration set between the range of 124-138 mEq/L
and dietary counselling should limit salt intake. 6
More controversial is the choice of surrogate clinical outcomes to use when assessing the
quality of volume management. Undoubtedly left ventricular hypertrophy is a consequence

of long-standing hypertension and fluid overload and thus a legitimate target for optimal
fluid management. There is, however, poor evidence that reducing left ventricular mass
translates into clinical benefit7 whereas medical treatment of hypertension is associated
with better outcomes.8 It is also an example of a disease-centred approach to managing
fluid status that runs the risk of putting one particular consequence of fluid overload, albeit
a very important one, ahead of outcomes that might be even more important to patients.
Daily dialysis might be good for left ventricular mass but comes at a treatment burden cost.
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Equally, in order to maximally protect the heart or other organs from hypertensive damage
or fluid excess (e.g., pulmonary oedema), the optimal strategy may be to set the post-
dialytic weight below the normally hydrated weight, i.e., cause volume depletion, whereas
when protecting against dialysis related symptoms the opposite strategy must be adopted,
with its inherent risks.
Perhaps most importantly, it is now recognised that preservation of residual kidney function
is of value to haemodialysis patients,9 yet it is infrequently measured and rarely considered
when prescribing dialysis. This is remarkable given the survival and quality of life benefits
associated with residual kidney function, long appreciated in peritoneal dialysis patients.
Aggressive fluid management strategies that do not take residual function into account run
the risk of accelerating its loss and there is an urgent need for trials of fluid management
strategies that might preserve it for as long as possible. Conversely, there are people on
dialysis who are at risk of dying during the 3-day break and it is likely that at least some of
those are at risk because of fluid excess, either directly because of pulmonary oedema or
indirectly via cardiac damage. It is clear that a one-size fits all strategy for volume
management cannot deliver what is needed.

The role of technologies
The single most important technological advance in volume management was the advent of
volumetric ultrafiltration. The combination of a balanced pump system, a pair of pumps

separated by a flexible membrane so that the dialysate flow in and out of the dialyser can
be perfectly matched, with the addition of a volumetric ultrafiltration pump meant that
fluid removal during dialysis could be controlled precisely. Its introduction meant that the
rate of fluid removal could now be controlled, which previously was done by monitoring
weight change in response to positioning of the dialysis membrane. It had a major impact
on the safety and symptoms associated with dialysis, but also contributed to the drive to
shorten dialysis treatments my maximising ultrafiltration rates. The replacement of acetate
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with bicarbonate as the dialysate buffer also had significant benefits on intra-dialytic
cardiovascular stability during dialysis, of particular value in an increasingly comorbid
population. Acetate infusion causes a drop in blood pressure and is also associated with
nausea on dialysis.
Both of these innovations became well established in the 1980s, whereas later technologies
designed to help with volume management have been less universally adopted. These
include haemodiafiltration, reported to reduce the incidence of intradialytic hypotension
and improved survival - although still the subject of major trials in Europe, and devices
designed to help with fluid management. These are intended to give the clinician insight
into the fluid status and so provide support in the setting of the target weight. They include
intra-dialytic relative blood volume monitoring, bioimpedance technologies and other
methods of measuring extravascular tissue fluid accumulation such as lung ultrasound.
Relative blood volume monitoring exploits the idea that removal of fluid from the
circulation by ultrafiltration will increase the haematocrit unless it is matched by plasma
refilling from the interstitial extravascular fluid compartment. In theory, at least, once the
refilling stops catching up with the ultrafiltration then the patient is at their target weight,
and pattern recognition of the relative blood volume curve can be useful. Bioimpedance
exploits the fact that when an alternating current is passed through tissues it will meet less
resistance from overhydrated interstitium but will be impeded by tissues whose cell

membranes act as mini capacitors. Again, in theory, it can be used to estimate the total
body water and the proportion of this that is intra- verses extra-cellular. Lung ultrasound
uses ‘comets’ to detect extravascular lung fluid, so identifying subclinical pulmonary
oedema.
What all these methods share is an ability to identify patients at risk and it is clear that
tissue fluid excess, often subclinical, is associated with worse outcomes in haemodialysis
patients. This appears to be independent of inflammation and blood pressure but is as much
a function of abnormal fluid distribution as it is of positive fluid balance (see Table 2), a
feature of many chronic diseases that are associated with protein energy wasting. Indeed,
loss of muscle mass of whatever cause, including deliberate or poverty associated
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starvation, does not lead to a proportional reduction in the extracellular fluid volume. 10 As
clinicians we can influence fluid balance through the dialysis prescription but changing how
fluid is distributed in the body is far more challenging. Trials evaluating these methods as
useful guides to fluid management, including relative blood volume monitoring,1
bioimpedance11 and lung ultrasound have not been promising overall. 10 As such, these
technologies should only be used in conjunction with a holistic clinical fluid assessment. 10
Looking to the future

Given these limitations, changes in case mix and need to focus on the experience of dialysis,
where are we going with volume management? 13 The answer, surely, must be by taking a
risk stratification approach that can accommodate individualized patient goals. This requires
accurate diagnosis of the problem – e.g., is it a fluid balance or fluid distribution problem (or
both, Table 2), and a systematic approach to holistic fluid management that is underpinned
by evidence. This requires the testing of approaches tailored to different risk groups
through the conduct of robust trials, which despite being difficult to undertake are much
needed. Technologies should steer away from non-stratified absolute target weight goals,
be tested in different risk groups and then develop artificial intelligence ultrafiltration
profiling and/or feedback methodologies that are more likely to work successfully. Dialysis
facilities need to find ways of design their services so that flexibility can be accommodated –
alternate day sessions for some patients, minimal care walk-in sessions that enable fluid

management on demand or incremental dialysis for those with varying need or significant,
documented residual kidney function. Finally, easy-to-use home dialysis machines and the
growth of successful home haemodialysis programmes are needed.
Disclosures
S.J. Davies reports the following: Consultancy: Ellen Medical; Research Funding: National
Institute of Health Research (UK); Kidney Research UK, EU Horizon 2020; Baxter HealthCare;
Honoraria: Baxter HealthCare, Fresenius Medical Care; Advisory and Leadership Role:
International Society of Peritoneal Dialysis (Member, co-chair PDOPPS Committee);
International Society of Nephrology (Kidney Failure Strategy); President EuroPD, Trustee
Kidney Research UK.
Acknowledgments
The content of this article reflects the personal experience and views of the author(s) and
D/g== on 05/21/2023
should not be considered medical advice or recommendation. The content does not reflect
the views or opinions of the American Society of Nephrology (ASN) or Kidney360.
Responsibility for the information and views expressed herein lies entirely with the
author(s).

References:
1. Davenport A. Why is intra-dialytic hypotension the commonest complication of
outpatient dialysis treatments? Kidney Int. Reports 2022.
2. Ju A, Unruh M, Davison S et al. Establishing a Core Outcome Measure for Fatigue in

Patients on Hemodialysis: A Standardized Outcomes in Nephrology-Hemodialysis (SONG-

HD) Consensus Workshop Report. Am. J. kidney Dis. Off. J. Natl. Kidney Found. 2018; 72:
104–112.
3. Rayner HC, Zepel L, Fuller DS et al. Recovery time, quality of life, and mortality in
hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am. J.
Kidney Dis. 2014; 64: 86–94.
4. Morton RL, Sellars M. From patient-centered to person-centered care for kidney diseases.
D/g== on 05/21/2023
Clin. J. Am. Soc. Nephrol. 2019; 14: 623–625.

5. Dasgupta I, Farrington K, Davies SJ et al. UK National Survey of Practice Patterns of Fluid
Volume Management in Haemodialysis Patients: A Need for Evidence. Blood Purif. 2016; 41:
324–31.
6. Weiner DE, Brunelli SM, Hunt A et al. Improving clinical outcomes among hemodialysis
patients: a proposal for a “volume first” approach from the chief medical officers of US
dialysis providers. Am. J. kidney Dis. Off. J. Natl. Kidney Found. 2014; 64: 685–695.
7. Badve S V., Palmer SC, Strippoli GFM et al. The Validity of Left Ventricular Mass as a
Surrogate End Point for All-Cause and Cardiovascular Mortality Outcomes in People With
CKD: A Systematic Review and Meta-analysis. Am. J. Kidney Dis. 2016; 68: 554–563.
8. Heerspink HJL, Ninomiya T, Zoungas S et al. Effect of lowering blood pressure on
cardiovascular events and mortality in patients on dialysis: a systematic review and meta-
analysis of randomised controlled trials. Lancet 2009; 373: 1009–1015.
9. Obi Y, Rhee CM, Mathew AT et al. Residual Kidney Function Decline and Mortality in
Incident Hemodialysis Patients. J. Am. Soc. Nephrol. 2016; 27: 3758–3768.
10. Davies SJ. The Elusive Promise of Bioimpedance in Fluid Management of Patients
Undergoing Dialysis. Clin. J. Am. Soc. Nephrol. 2020: CJN.01770220.
11. National Institute for Health and Care Excellence. Multiple frequency bioimpedance
devices to guide fluid management in people with chronic kidney disease having dialysis.
2017.

12. Zoccali C, Torino C, Mallamaci F et al. A randomized multicenter trial on a lung
ultrasound–guided treatment strategy in patients on chronic hemodialysis with high
cardiovascular risk. Kidney Int. 2021; 100: 1325–1333.
13. Flythe JE, Chang TI, Gallagher MP et al. Blood pressure and volume management in
dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO)

Controversies Conference. Kidney Int. 2020; 97: 861–876.
D/g== on 05/21/2023

Table 1. Summary of past, present, and future states of volume management
Past Present Future

Case Mix Younger, less multi- Older, multi-morbid Increasing proportion
morbid population, able population, frequently of old, frail and
to tolerate large volume hypotensive and with muscle wasted multi-

losses, typically more complex fluid morbid population in

hypertensive distribution challenges high income settings
and a stiff arterial and a global epidemic
circulation of diabetes
Disease-centred Patient-centred care Person-centred care.

Inclusion of approach – focussed recognised and Co-production of
Patient’s on lab measures and measures of treatment plans and
Priorities normalisation of important outcomes prioritisation of patient
objective measures e.g., intra-dialytic reported outcomes,
(e.g., BP, LV Mass, Hb) hypotension and post e.g., fatigue, post
One size fits all dialysis recovery dialysis recovery
approach that often did included in treatment
not take the patient goals
D/g== on 05/21/2023
perspective into
account
Prescription dominated Recognition that Volume management

Problem by solute clearance volume status (over- as a complex
Recognition Little attention to hydration) is as, or intervention that
residual kidney function more important than requires risk
solute clearance, that stratification. Requires
high ultrafiltration validation of tools to
rates are harmful, and support this approach
both fluid balance and and an evidence base
fluid distribution are
critical
Treatment Prescription often More frequent dialysis Negotiated (e.g., goal

designed to shorten and avoidance of directed) personalised
Strategies hours maximising excessive fluid gains approach that is risk
solute clearance and and methods to avoid based (e.g., the 3-day
divining target weight intra-dialytic break increased
by using volume hypotension (Na mortality), and takes
management to control modelling, dialysate residual kidney
BP. temperature). function into account
(e.g., incremental start
to dialysis)
Role of Focus on dialysis Growing use of Volume assessment

Technologies machine technology bioimpedance, lung tools will find their
and delivery benefits ultrasound and place as a component
e.g., bicarbonate intradialytic relative in the individualisation
dialysate, blood volume of care
volumetric ultrafiltration, monitoring which help Realtime intelligent
EPO, dialysate identify problems but feedback devices
temperature regulation, are yet to be Easy to use home
haemodiafiltration. demonstrated to add dialysis machines and
value in management wearable technologies
of fluid status

Table 2: Categorising the challenge of volume management by fluid balance
versus fluid distribution
Fluid Balance Predominates Fluid Distribution Predominates

Positive Balance:
 Excessive salt (and water) intake  Muscle wasted, frailty
 Large intra-dialytic weight gains  Diabetic/Autonomic Neuropathy
 Requiring high ultrafiltration rates  Cardiac dysfunction
(e.g., >10-13 ml/h/kg) o reduced ejection fraction: risk
 Anuria of pulmonary oedema,
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Negative balance: o preserved ejection fraction:

 Inadequate fluid and nutritional may require higher filling
intake pressures to avoid
 Diarrhoea or vomiting hypotension
 high urine volume  Inflammation
 Acute blood loss  Hypoalbuminaemia

 Sepsis

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IMuo2hXmffFQ0IhrVKdI6wDqfuJKUdg1tsKAyF7JXOXvQ1kT29V+INqs2RM49V59cdDjUkH6dwrf4S2HemMr8th15tr2fgxsK7f2

Downloaded from http://journals.lww.com/kidney360 by MSIG3rXgKaZWXkDH4MWaerB1tJF2b+k8Zv4zpDJNLecXmGg

Authors: Simon J. Davies

Title: Volume management in hemodialysis – a moving target

Manuscript Type: Perspective

Manuscript Category: Dialysis

Funders: There was no external financial support for this article

Study Group/Organization Name:

Study Group Members’ Names:

Copyright © 2023 by the American Society of Nephrology

Copyright © 2023 by the American Society of Nephrology

Volume management in hemodialysis – a moving target

Professor of Nephrology and Dialysis medicine,

Keywords: blood pressure, fatigue, person-centered care, intradialytic

reproduction in any medium, provided the original work is properly cited.

Copyright © 2023 by the American Society of Nephrology

My first exposure to haemodialysis was in 1976 when, as a first-year medical student I

Copyright © 2023 by the American Society of Nephrology

Copyright © 2023 by the American Society of Nephrology

quality of volume management. Undoubtedly left ventricular hypertrophy is a consequence

Copyright © 2023 by the American Society of Nephrology

volumetric ultrafiltration. The combination of a balanced pump system, a pair of pumps

Copyright © 2023 by the American Society of Nephrology

Looking to the future

Copyright © 2023 by the American Society of Nephrology

Copyright © 2023 by the American Society of Nephrology

2. Ju A, Unruh M, Davison S et al. Establishing a Core Outcome Measure for Fatigue in

Patients on Hemodialysis: A Standardized Outcomes in Nephrology-Hemodialysis (SONG-

Clin. J. Am. Soc. Nephrol. 2019; 14: 623–625.

Copyright © 2023 by the American Society of Nephrology

dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO)

Copyright © 2023 by the American Society of Nephrology

Past Present Future

to tolerate large volume hypotensive and with muscle wasted multi-

losses, typically more complex fluid morbid population in

Disease-centred Patient-centred care Person-centred care.

Prescription dominated Recognition that Volume management

Treatment Prescription often More frequent dialysis Negotiated (e.g., goal

Role of Focus on dialysis Growing use of Volume assessment

Copyright © 2023 by the American Society of Nephrology

Fluid Balance Predominates Fluid Distribution Predominates

Negative balance: o preserved ejection fraction:

 high urine volume  Inflammation

 Acute blood loss  Hypoalbuminaemia

Copyright © 2023 by the American Society of Nephrology

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