Kidney disease:

A UK public health
emergency
The health economics of
kidney disease to 2033
June 2023
Disclaimer

This report has been co-funded by Kidney Research UK and the following industry
supporters: AstraZeneca, CSL Vifor, GSK, Hansa Biopharma and Proteomics.
These companies had no control or editorial input to the contents of this report.

This report and the analysis contained herein have been produced on a “best
efforts” basis. Neither Kidney Research UK nor ZS Associates International, Inc.
(or any of their affiliates) accepts any liability arising out of or in connection
with third-party use of the report and its contents. The name, logos and
trademarks of ZS Associates as appearing herein are owned by ZS Associates
and shall not be used, in any manner whatsoever, without the prior written
consent of ZS Associates, which consent may be reasonably withheld by ZS
Associates at its sole discretion.

Kidney Research UK
Charity registration no. 252892 (England and Wales) SC 039245 (Scotland)
www.kidneyresearchuk.org

Recipients (journals excepted) are free to copy or use the material from this report, provided
that Kidney Research UK is acknowledged as the source.

2
Contents
Acknowledgements 07
About this report 08
Foreword by Professor Sir Stephen Powis 09
Key Findings 10
Executive Summary 11
Background 25
Introduction: Kidney disease, the silent crisis 25
Kidney disease policy and research 28
Scope of this report 29
Overview of Kidney Disease 30
Chronic kidney disease 30
Acute kidney injury 32
End stage kidney disease 33
Rare kidney diseases 36
Paediatric kidney diseases 41
Risk Factors 43
Clinical risk factors for kidney disease 43
Demographic and inequality risk factors 46
Covid-19-associated risk factors 48
Methodology 51
Overview of approach 51
Detailed method: stakeholder engagement 53
Detailed method: targeted literature review 55
Detailed method: epidemiological modelling 57
Detailed method: health economic modelling for CKD (all stages) 60
Epidemiology of kidney disease 65
CKD 65
Dialysis (adult and paediatric) 67
Transplantation (adult and paediatric) 69
Acute kidney injury 71
Paediatric kidney disease 72
Rare kidney disease 72

3
The current and future economic burden of kidney disease 73
Overview 73
The cost of CKD 76
The cost of dialysis 76
The cost of kidney transplantation 76
The cost of dialysis and transplantation to the UK economy 77
The cost of AKI 77
The cost of paediatric kidney diseases 77
The cost of rare kidney diseases 78
Interventions to manage the burden of CKD 79
Combined impact 80
Intervention 1: early/improved diagnosis 85
Intervention 2: improved CKD management 87
Intervention 3: use of SGLT-2 inhibitors 89
Intervention 4: increased rates of transplantation 90
Scenario and sensitivity analysis 93
Conclusions and recommendations 96
Conclusions 96
Recommendations 97
Acronyms 100
Definitions 102
References 103
Appendix A – TLR protocol summary 113

4
Tables
Table 1. Stages of chronic kidney disease 26
Table 2. NHS funding and research cost for kidney disease 28
Table 3. Guide to frequency of monitoring (number of times per year) 31
by eGFR and albuminuria
Table 4. Top 20 rare kidney conditions in the UK 36
Table 5. Support needed for children with CKD 42
Table 6. Outcomes captured within each health state for CKD 52
Table 7. Prevalence of CKD stage 3-5 by age group 58
Table 8. Estimated prevalence of rare kidney disease in the UK 72
Table 9. Clinical impact of combined interventions 81
Table 10. Economic impact of combined interventions 81
Table 11. Clinical impact of intervention 1 86
Table 12. Economic impact of intervention 1 86
Table 13. Clinical impact of intervention 2 88
Table 14. Economic impact of intervention 2 89
Table 15. Clinical impact of intervention 3 90
Table 16. Economic impact of intervention 3 90
Table 17. Clinical impact of intervention 4 92
Table 18. Economic impact of intervention 4 92

5
Figures
Figure 1. Representation of transplant waiting list over 5-year period 34
Figure 2. Prevalence of diabetes in the UK (2014-2019) 43
Figure 3. Diagram of flowchart methodology 51
Figure 4. Diagram of stakeholder engagement process 53
Figure 5. Preferred Reporting Items for Systematic Reviews and Meta-Analyses 56
(PRISMA) flow diagram (search hits and attrition)
Figure 6. Growth in CKD prevalence in the UK 58
Figure 7. Health economic model schematic 61
Figure 8. Health model to capture interventions affecting the disease pathway 62
Figure 9. Epidemiology of CKD stages 1-5 (excluding transplantation and dialysis) 65
Figure 10. Growth in CKD prevalence in the UK 66
Figure 11. Current and future projections of dialysis in adults with ESKD in the UK 67
Figure 12. Constrained vs unconstrained projections of dialysis in adults with ESKD in the UK 68
Figure 13. Adults with ESKD on dialysis (UK population, 2020) 68
Figure 14. Constrained vs unconstrained projection of adults receiving 69
kidney transplants in the UK (2033)
Figure 15. Current and future projections of AKI episodes in the UK 71
Figure 16. Economic burden of kidney disease in the UK 74
Figure 17. Bridge reconciling differences in key drivers of total costs 75
in this 2023 report and the 2012 NHS report
Figure 18. QALYs gained by intervention 82
Figure 19. Incremental direct costs by intervention 83
Figure 20. Summary of ICERs in the unconstrained view 84
Figure 21. Intervention 1 schematic: early/improved diagnosis 85
Figure 22. Projected ICER for intervention 1 87
Figure 23. Intervention 2 schematic: improved CKD management 88
Figure 24. Intervention 3 schematic: use of SGLT-2i to reduce CVD events 89
and progression to ESKD
Figure 25. Intervention 4 schematic: increased rate of transplantation 91
Figure 26. Comparison of ICERs for the combined interventions, constrained vs 94
unconstrained view
Figure 27. One-way sensitivity analysis 95

6
Acknowledgements
The contents of this report are ZS Associates independent findings based on the methodology
detailed within the document. Sincere thanks to the following leading UK experts for their
insights and expertise provided throughout this project:

Dr Ama Basoah* Dr Samira Bell*

General Practitioner, Kidney Research UK Lay Senior Clinical Lecturer and Honorary
Advisory Group Member, and Kidney Patient Consultant Nephrologist, University of Dundee

Dr Martin Christian* Professor Daniel Gale

Consultant Paediatric Nephrologist, St Peter’s Chair of Nephrology, Department of
Nottingham University Hospitals NHS Trust Renal Medicine, University College London

Dr Matthew Graham-Brown* Dr Jackie Gray

Clinical Associate Professor of Renal Medicine, Medical Specialist in Public Health
Department of Cardiovascular Sciences, and Primary Care, UK
University of Leicester
Vijay K. Luthra*
Dr Barnaby Hole Healthcare & Life Sciences Consultant and
University of Bristol Advisor, Kidney Research UK Development
Advisory Board Member and Kidney Patient
Dr Viyaasan Mahalingasivam*
Research Fellow, Department of Dr Kieran McCafferty
Non-communicable Disease Epidemiology, Consultant Nephrologist, Barts Health NHS Trust
London School of Hygiene & Tropical Medicine
Dr Dorothea Nitsch
Dr James Medcalf* Professor, London School of Hygiene
Consultant, UK Renal Registry and Tropical Medicine

Professor Gurch Randhawa* Dr Simon Sawhney

Professor of Diversity in Public Health and Sr Clinical Lecturer, University of Aberdeen
Director, Institute for Health Research,
University of Bedfordshire Professor Smeeta Sinha*
National Clinical Director Renal Medicine,
Professor Nicholas M Selby NHS England, and Consultant Nephrologist,
Professor of Nephrology, University of Salford Royal Hospital, Northern Care Alliance
Nottingham, and Honorary Consultant, NHS Foundation Trust
Nephrologist Royal Derby Hospital

Professor Laurie Tomlinson*

Faculty of Epidemiology and Population Health,
Department of Non-communicable Disease
Epidemiology

* These stakeholders were members of the steering committee, a smaller group of ten clinicians,
academics and patients who met regularly between February 2023 and April 2023 to guide
the project and validate the key findings.
7
About this report
Kidney Research UK commissioned ZS Associates to prepare an independent
report on the health economics of kidney disease and associated factors in the
UK in 2022. The report includes modelling of some illustrative interventions for
adults with chronic kidney disease, risk factors associated with chronic kidney
disease and changes in the health economic burden of treatment of kidney
disease over the next ten years. Kidney disease is a major challenge for health
care systems around the world, and its prevalence is increasing. There have
been various papers prepared on the health economics of kidney disease in the
UK, although there has not been a comprehensive report prepared since 2012.
This report was prepared by ZS Associates in collaboration with Kidney Research
UK and the expert advisory steering group in 2023.

About Kidney Research UK

Kidney Research UK is the leading charity in the UK focused on funding
research into the prevention, treatment and management of kidney disease.

Our vision is the day when everyone lives free from kidney disease and for
more than 60 years the research we fund has been making an impact.

But kidney disease is increasing as are the factors contributing to it, such as diabetes,
cardiovascular disease and obesity, making our work more essential than ever.

At Kidney Research UK we work with clinicians and scientists across the UK, funding
and facilitating research into all areas of kidney disease. We collaborate with
partners across the public, private and third sectors to prevent kidney disease and
drive innovation to transform treatments.

Over the last ten years we have invested more than £58 million into research.
We lobby governments and decision makers to change policy and practice to
ensure that more than 3 million people living with the most severe stages of
kidney disease in the UK have access to the most effective care and treatment,
and to make kidney disease a priority.

Most importantly, we also work closely with patients, ensuring their voice is
heard and is at the centre of everything we do, from deciding which research
to invest in to how we plan our priorities and our work across the charity.

Those patient contributions are vital, always helping us and our partners to
understand what life is like with kidney disease, always ensuring we see the patient
behind the treatment and always reminding us that behind every statistic and every
number is a person – the patients and the carers who inspire our mission and
push us forward to make a difference and change the future of kidney disease.

8
Foreword
Professor Sir Stephen Powis
National Medical Director of NHS England
Professor of Renal Medicine at University College London

This is the most comprehensive review of the health economics

of kidney disease in the UK for more than ten years. At a time of
unprecedented health system pressures, and an ageing population, this
report is timely and welcome. Kidney disease is on the increase and there
is no cure. It is a life changing disease that can put a significant strain on
the body, often referred to as the silent killer, and yet it is not as widely
recognised or acknowledged as other long-term conditions.

Globally, kidney disease is forecast to be the fifth leading cause of premature

death by 2040, and often progresses undiagnosed, until its later stages, due to a
lack of symptoms. It can affect anyone. In the UK, more than three million people
are living with the most severe stages of kidney disease and this is increasing
rapidly. Factors contributing to kidney disease are also growing, such as diabetes,
cardiovascular disease and obesity, and people with kidney disease are also at
increased risk of heart attack or stroke. The case for action is more urgent than
ever. The later the diagnosis, the greater the impact on the patient.

In its late stages, kidney disease is life changing for patients, with few
treatment options available. There is an enormous impact on quality of life for
patients and for their families and carers, in addition to significant emotional
and financial burdens.

Until a cure for kidney disease is developed, only early diagnosis, new and
effective prevention strategies and better management of kidney disease can
reduce its incidence and slow progression.

This report estimates that the current economic burden of kidney disease to
the UK is £7bn with £6.4bn of this related to direct NHS costs; these figures
could grow to as much as £13.9bn and £10.9bn, respectively by 2033.

This report serves as a stark call to action for stakeholders across the public,
private, academic and health sectors to come together to implement its
recommendations, improve prevention, management and treatment, and
drive the research and innovation that could end kidney disease.

Professor Sir Stephen Powis

9
Key Findings
1 In the UK, there are
approximately 3.25 million
people living with chronic kidney
disease (CKD) stages 3-5. A further
3.9 million people are estimated to have CKD
2 By 2033, the number
of people with CKD
stages 3-5 is projected to
stages 1-2. Together reaching a total of 7.2 million
– more than 10% of the entire population.
reach 3.9 million. This is
mainly driven by an ageing
population, as well as risk factors
such as diabetes, hypertension and
3 Around 615,000 episodes of
acute kidney injury occur each
year; mainly among people who
cardiovascular disease and other are already unwell or hospitalised
important factors such as health for another reason.
and economic inequalities.

4 A total of 30,000 adults and children are on

dialysis due to kidney failure and lose at least 12
hours per week of work and leisure time (dialysing 5 Dialysis is a key driver of
the economic burden of
three sessions a week, 4 hours per kidney disease, estimated to
session). The number of patients cost the NHS £34,000 per year
requiring dialysis could rise to per patient in 2023 – more than
143,000, while the demand for three times the annual value of a
transplantation could be as high state pension.
as 12,000 per year by 2033.

6 The total annual

economic burden of
kidney disease in the UK is
7 People living with CKD and those who
support them experience a dramatic
impact in their daily lives, with £372 million
£7.0 billion, with £6.4 billion in productivity loss to the UK economy annually
being direct costs to the NHS from missed work due to dialysis alone.
– about 3.2% of NHS budgets. This could rise to £2.0 billion by 2033.

8 Kidney disease is currently the tenth biggest

killer worldwide and is projected to be the
fifth highest cause of life years lost by 2040.
10 Modelling
suggests
that improved
implementation of
four illustrative kidney-related
healthcare interventions

9 Despite the large and rapidly growing

burden of kidney disease, it received only 1.4%
of relevant public healthcare research funding –
alone could save more than
10,000 lives between 2023
and 2033 in the UK and
just £17.7 million – in financial year 2021/ 2022. would be cost effective.

10
Executive Summary
Background

The kidneys are master regulators and essential for life, when they fail, the
result is devastating. Responsible for a multitude of functions, kidneys are vital
organs, yet Kidney Research UK’s own research has found that 80% of people
don’t know where they are or what they do. The kidneys are located on either
side of the spine, and they are responsible for hormone secretion into the
bloodstream, removing waste, toxins and excess fluids from the blood.

The term “kidney disease” encompasses a broad range of conditions that

leads to poor kidney function. Since the kidneys are necessary for many bodily
functions, kidney disease increases the risk of developing other diseases, and
conversely other diseases are risk factors for kidney disease. There is no cure for
kidney disease, and managing it is a complex task, as kidney abnormalities exist
across every age group, gender and ethnicity and can appear without warning.

Kidney disease is often labelled as a silent killer due to its frequent lack of
physical symptoms, and as this report demonstrates is fast becoming a crisis.
Even when symptoms are present, they are often overlooked or attributed to
a differential diagnosis or other health issues. Since early diagnosis is key to
managing and slowing progression to kidney failure, patients face devastating
consequences if symptoms go undiagnosed. The majority of kidney diseases
can be characterised as acute kidney injury, chronic kidney disease or end-
stage kidney disease.

Acute kidney injury is a rapid deterioration in kidney function and typically

occurs in people who are hospitalised, especially those who require treatment
in intensive care units. Acute kidney injury causes a build-up of waste products
in the blood, affecting other organs such as the brain, heart, and lungs. Acute
kidney injury requires most patients to be hospitalised for kidney function
to recover and in most cases is reversible. However, it is recognised as an
important risk factor for progression of chronic kidney disease.

Chronic kidney disease is usually categorised into five stages (Table E1).

11
Table E1. Stages of chronic kidney disease

Stages of chronic % of kidney

Symptom/implication
kidney disease function

Kidney damage
STAGE 1 with normal
kidney function • People in early-stage CKD may not
100-90%
know they have CKD as they often feel
Kidney damage well and show no symptoms
STAGE 2 with mild loss of
kidney function
89-60%

Mild to moderate
STAGE 3a loss of kidney
function
59-45%
• People are often diagnosed with kidney
Moderate to disease in the mid-stage, with many
STAGE 3b severe loss of people still asymptomatic as waste in
kidney function 44-30% the body builds and blood pressure rises

Severe loss of
STAGE 4
kidney function
29-15%

• Patients with kidney failure require dialysis*

or a kidney transplant to stay alive
• A proportion of people with kidney
STAGE 5 Kidney failure failure will not receive either dialysis
or transplant, instead undergoing
Less than 15%
conservative care

*Dialysis is a type of kidney replacementtherapy that replaces the blood-filtering function ofthe kidneys.

Chronic kidney disease affects more than 10% of the UK population and is rapidly
becoming more common as the population ages. Despite its high prevalence, early
detection and awareness are low, in part because of an absence of early symptoms.

Many health conditions can contribute to chronic kidney disease, but two primary risk
factors are diabetes and high blood pressure. Diabetes and the accompanying high
levels of blood sugar can damage various organs in the body, including the kidneys
and heart. High blood pressure, or hypertension, damages blood vessels throughout
the body, including those in the kidneys. When these blood vessels are damaged,
the kidneys are less effective at removing waste and excess fluid from the body.

12
In addition to clinical risk factors, there are environmental and social factors that
contribute to an increased risk of developing chronic kidney disease. These factors
include access to healthcare, societal inequalities, and biological, genetic and
cultural factors. Rare and genetic forms of kidney disease collectively affect a
large number of people, while health inequalities make it challenging for people
to receive the medical attention, access to care and support they need. In the UK,
some groups are particularly at a disadvantage when it comes to kidney care. It is
well established that people from lower socio-economic groups, in some instances
ethnic minority groups, are more likely to develop chronic kidney disease, progress
faster towards kidney failure and die earlier. People from some ethnic minority
groups are three to five times more likely to require dialysis and wait much longer for
a kidney transplant on average than people from a white background.

Complications associated with kidney disease can accelerate progression and

increase the risk of cardiovascular-related events. As chronic kidney disease
worsens and becomes kidney failure (end-stage kidney disease), dialysis or
kidney transplantation is required to survive.

End-stage kidney disease is defined by permanent kidney damage, and kidney

function is reduced to 15% or less. Patients may experience a variety of symptoms
which include fatigue, drowsiness, reduction or absence of urine production,
itchy skin, headache, weight loss, nausea, bone pain, skin and nail changes and
easy bruising. This stage is ultimately fatal and requires either dialysis or a kidney
transplant. The number of people with end-stage kidney disease requiring kidney
replacement therapy is increasing worldwide and is predicted to double by 2030.

To date in 2023, there are 30,000 people in the UK who rely on dialysis to stay
alive. There are two main types of dialysis to manage end-stage kidney disease
– haemodialysis and peritoneal dialysis. In the UK, the majority (72%) of the 7,500
adults a year starting kidney replacement therapy begin with haemodialysis,
where an artificial kidney machine is used to clean the blood. Most people
receiving haemodialysis dialyse three times a week for four hours at a time. The
other main form of dialysis, peritoneal dialysis, uses the lining of the abdomen
(peritoneum) to filter the blood. In 2020, around 3,800 patients in the UK were
on peritoneal dialysis.

An alternative treatment for patients with kidney failure is a kidney transplant.

In the UK, over 2,900 adult transplants and 100 paediatric transplants are
performed annually. For adult patients waiting for a kidney transplant, the
average time frame is 2-3 years, with about 4,600 patients on the waiting list in
2022. On average, a transplant from a deceased donor lasts 15-20 years and a
transplant from a living donor around 20-25 years, with the longevity affected
by a variety of factors including age, health and other multi-morbid risk factors
including diabetes and cardiovascular complications.

Despite the high prevalence and burden of kidney disease, research spending
is relatively low, at just 1.4% (£17.7 million) of relevant publicly funded research
budgets in the financial year 2021/22. A systematic analysis of the economic
burden of kidney disease has not been undertaken in the UK, since 2012.

13
Scope of this report

Kidney Research UK commissioned ZS Associates to prepare a report

investigating the following topics:
• The current kidney disease landscape in the UK, including acute, chronic and
end-stage kidney disease, as well as rare and paediatric kidney diseases
• The current management strategies, risk factors, health of people from
socially deprived communities, and the impact of Covid-19 on the kidney
patient population
• The current incidence and prevalence of acute, chronic and end-stage
kidney disease in the UK
• The current and projected (2033) economic burden of kidney disease,
for both NHS and the wider UK economy

Approach

The diagram below shows the key steps taken to develop this report (Figure E1).

Figure E1. Project approach

1. 30 contributing stakeholders with a 2. Targeted literature review of 11,000

steering committee of ten UK articles from the last 5 years

3. Epidemiological modelling 4. Health economic modelling for CKD

using a population-level Markov model

14
1. Over 30 stakeholders contributed to the development of this report.
Stakeholders were recruited from various backgrounds, including
nephrologists, cardio-renal specialists, kidney transplant specialists,
paediatric nephrologists, primary care physicians, nephrology clinical
service directors, academics, data specialists and patients. Stakeholder
engagement played a pivotal role in shaping the inputs of this report and
validating the outputs. Stakeholder engagement began with a series
of scoping meetings from December 2022 to January 2023. A smaller
steering group of ten clinicians, academics and patients met regularly
between February 2023 and April 2023 to guide the project and validate
the key findings.

2. A targeted literature review was conducted to comprehensively gather

the most up-to-date, publicly available evidence. The targeted literature
review search strategy aligned with previously defined standards and was
based on predefined reproducible search strings for epidemiology and
economic literature reviews. The search identified approximately 11,000
UK-based articles published in the last 5 years. In some cases, additional
targeted searches were performed to find model parameters. Additional
evidence was provided through stakeholders in the scoping meetings and
steering committee meetings.

3. The purpose of epidemiological modelling was to understand the historic

trends in incidence and prevalence of the various conditions under the
banner of kidney disease, and to calculate estimates of future demand
and disease burden. The approach taken was to analyse several years of
historic trends and changes in patient demographics. The modelling also
examined the known impact of Covid-19 on these patient populations from
2020 to 2022. Because it is based on historical activity data, the projections
from the epidemiological modelling will incorporate any existing capacity
constraints – they will not factor in any unmet need. This is a particular risk
for projections of transplantation and dialysis as they may underestimate
the true level of future need, and for that reason additional unconstrained
projections were produced using the health economic model.

4. A population-level health economic model (Markov model) was used

to estimate the current and future incidence/prevalence and economic
burden of chronic kidney disease across all stages and show the directional
impact of illustrative interventions based on costs and outcomes. The
model was developed to capture both NHS (direct cost) and UK economy
(wider economic cost) perspectives. The time horizon for the model was
set to 10 years. In addition to this baseline, the model was used to estimate
the impact of four potential public health interventions: earlier diagnosis,
better adherence to clinical guidelines, increased uptake of new medicines
and increased rates of transplantation.

15
Findings

Epidemiology of kidney disease

The prevalence of the various types and stages of kidney disease has grown
considerably in recent years and will continue to do so. Factoring in the ageing
population and excess deaths in high-risk populations during the Covid-19
pandemic, an estimated 7.19 million people in the UK have chronic kidney
disease in 2023, more than 10% of the UK population. By 2033, this will
increase to 7.61 million people. While the overall prevalence as a proportion
of the age 16+ population is expected to remain constant, among the people
with chronic kidney disease, the proportion of patients with later-stage chronic
kidney disease is expected to increase from 45% to 51% (Figure E2).

Figure E2. Epidemiology of chronic kidney disease stages 1-5 (excluding

transplantation and dialysis)
Figure E2. Epidemiology of chronic kidney disease (CKD) stages 1-5
(excluding transplant and dialysis)

2023 3.9M (55%) 3.2M (45%) 7.19M

2033 3.8M (49%) 3.9M (51%) 7.61M

0.0 2.0 4.0 6.0 8.0

People living with CKD Stages 1-5 (in millions)

CKD 1-2 CKD 3-5

16
 Rates of acute kidney injury will also continue to grow, although more slowly
than chronic kidney disease. Based on historic trends, the incidence of acute
kidney injury will increase from an estimated 615,000 episodes in 2022 to
637,000 by 2033.

For dialysis and transplantation, a broad range of potential future demand

was calculated. The constrained view assumes NHS capacity continues to
grow at current rates based on the actual numbers of patients treated over the
past 10 years, while the unconstrained view estimates the number of people
who may need dialysis based on how quickly people progress through the
stages of kidney disease. In the unconstrained view of demand, which factors
in all potential unmet need, the number of patients requiring dialysis could rise
to 143,000, while the demand for transplantation could be as high as 12,000
per year by 2033 (Figure E3).

Figure E3. Constrained vs. unconstrained projections of adults receiving

kidney transplants in the UK (2033)
Figure E3. Constrained vs. unconstrained projections of adults receiving kidney transplants in the UK (2033)

14,000

11,665
12,000

10,000
Patient population

8,000

6,000

3,615
4,000 2,976
2,863

2,000

0
2013 2015 2017 2019 2021 2023 2025 2027 2029 2031 2033
Years
Historic trend Constrained projection Unconstrained projection

17
Current and future economic burden of kidney disease
In 2023, the total cost of kidney disease to the UK economy is estimated at
£7.0 billion. This includes £6.4 billion in direct costs to the NHS, approximately
3.2% of the £197 billion of total NHS spending across the four nations. The £7.0
billion estimate also includes £372 million in productivity loss for people living
with end-stage kidney disease and those who support them, in addition to
£225 million of transport costs for patients receiving dialysis.

With the assumption that the current system is at its maximum capacity for
expensive end-stage kidney care such as dialysis and transplantation, the cost
of kidney disease will rise to £7.5 billion by 2033 (11% increase from 2023), with
the biggest increase in cost due to the increasing prevalence and associated
costs of chronic kidney disease stages 3-5. However, when modelling
unconstrained need, the health economic model projected that in 2033 the
cost could be as high as £13.9 billion, with the biggest driver being the growth
in demand for dialysis (Figure E4).
Figure E4. Economic burden of kidney disease in the UK
Figure E4. Economic burden of kidney disease in the UK

2023

2033 constrained view

2033 unconstrained view

£.0B £3.5B £7.0B £10.5B £14.0B

AKI CKD 1-2 CKD 3-5 Transplantation

Dialysis Transport Productivity

18
Modelling of interventions to manage the burden of chronic kidney disease
There is a growing body of evidence indicating that the burden of chronic kidney
disease can be reduced through early detection, pharmacological intervention
and outreach. A key objective for this report was to assess whether a basket of
potential population-level interventions for managing chronic kidney disease,
including end-stage kidney disease, could be cost-saving or cost-effective.

Through the stakeholder engagement process, several interventions were cited

as having the potential to improve clinical outcomes associated with chronic
kidney disease. The following interventions were applied to the model:

• Intervention 1. Early/improved diagnosis: This intervention targets

underserved populations through outreach programmes to improve
screening opportunities and increase early diagnosis and is illustrative of
the benefits which can be achieved through well-targeted early/improved
diagnosis in general.

• Intervention 2. Improved CKD management: This intervention targets

eligible patients with chronic kidney disease who are either untreated
or not receiving standard care according to clinical guidelines (e.g.
adequate blood pressure management).

• Intervention 3. Use of SGLT-2 inhibitors: This intervention aims to

increase uptake of new medications such as sodium-glucose transport
protein 2 (SGLT-2) inhibitors to reduce cardiovascular events and slow
progression to end-stage kidney disease.

• Intervention 4. Increased rates of transplantation: This intervention

models the impact of increased outreach and awareness to increase
pre-emptive live donor transplants. It is illustrative of the benefits of
improving transplantation rates more generally.

The combined impact of these interventions was to prevent more than 10,000
deaths over the 10-year time horizon, with 49,574 quality-adjusted life years
saved (Table E2). This is predicted to cost £7,688 per quality-adjusted life
years – significantly below the National Institute for Health and Care Excellence
willingness-to-pay threshold of £20,000-£30,000 per quality-adjusted life
year (QALY), meaning these interventions would be deemed cost effective.
The modelling also predicts that the reduction in indirect costs (travel and
lost economic productivity) of £445.7 million would more than offset the total
increase in NHS costs of £381.1 million. All of the interventions individually or
combined show a cost-effective or cost-saving Incremental Cost-Effectiveness
Ratio (ICER) (Figure E5).

19
Table E2. Economic impact of combined interventions in the unconstrained view

Scenario
Direct costs (£) Indirect costs (£) Total costs (£) QALYs
(Years 1-10)
Base case 70,683,534,208 20,334,744,603 91,018,278,811 71,662,137
Combined
71,064,652,248 19,889,062,335 90,953,714,583 71,711,711
Interventions
Difference 381,118,041 (445,682,268) (64,564,228) 49,574
% change 0.5% -2.2% -0.1% 0.1%

Figure E5. Summary of incremental cost-effectiveness ratios (ICERs) in the unconstrained view
Figure E5. Summary of incremental cost-effectiveness ratios (ICERs) in the unconstrained view

40,000

30,000
NICE ICER threshold (£20,000–£30,000)
20,000

10,000
ICER £

0
Intervention 1 Intervention 2 Intervention 3 Intervention 4 Combined Combined
interventions interventions
-10,000 (unconstrained) (constrained)

-20,000

-30,000
Cost-saving
-40,000

-50,000

20
Conclusions

The evidence presented in this report suggests that kidney disease leads to
thousands of premature deaths each year, reduces quality of life and places
a significant economic burden on the NHS, patients with kidney disease, the
people who support them and the wider economy:

1. Chronic kidney disease affects 13% of the global population and is

predicted to be the fifth leading cause of premature death* by 2040.
2. In the UK, approximately 3.25 million adults are living with chronic kidney
disease stages 3-5, and a total of 7.2 million adults have chronic kidney
disease (all stages), more than 10% of the entire population.
3. By 2033, the number of people living with all-stage chronic kidney
disease is projected to reach 7.6 million. This is mainly driven by an ageing
population as well as risk factors such as diabetes, hypertension and
cardiovascular disease, as well as other important factors such as health
and economic inequalities.
4. Amongst those with chronic kidney disease, the proportion with later-stage
chronic kidney disease (3-5) is expected to increase from 45% (3.25 million)
to 51% (3.9 million).
5. Around 615,000 episodes of acute kidney injury occur each year, mainly
among those who are already unwell or hospitalised for another reason.
By 2033, the number of acute kidney injury episodes is projected to rise by
4% to 637,000.
6. The total economic burden of kidney disease in the UK is £7.0 billion, with
£6.4 billion attributable to direct costs to the NHS – about 3.2% of NHS
budgets across the four nations. The total burden of kidney disease could
rise to £13.9 billion by 2033.
7. There is a further estimated £372 million in productivity loss to the UK
economy from from missed work due to dialysis alone. Productivity loss
in the UK could reach up to £2.0 billion by 2033, as a higher proportion of
patients continue living with end-stage kidney disease.
8. In 2023, the cost of dialysis for people with end-stage kidney disease
is £1.05 billion annually, or 0.53% of the NHS budget. In addition to the
direct cost of dialysis, transport for patients on in-centre dialysis costs
approximately £225 million per year. The cost to the NHS of dialysis to
manage kidney disease (per person) is £34,000 per year – more than
three times the annual value of a state pension.
9. Despite its substantial and increasing cost to the NHS, and the urgent need
for new and better treatments driven by research, kidney disease received
only 1.4% of relevant public healthcare research funding – just £17.7 million in
financial year 2021/2022.
10. Economic modelling suggests that improved implementation of four
illustrative healthcare interventions could save more than 10,000 lives by
2033. These interventions individually and collectively are shown to be
cost-effective or cost-saving, where costs to the NHS are offset by quality-
adjusted life years gained.
* Premature death can be measured by life years lost, which takes into account frequency of death and age at which it
occurs. It is calculated by multiplying the number of deaths by a global standard life expectancy at which death occurs.

21
Recommendations

Strategic
Modelling indicates that significant, cost-effective patient benefits can
be achieved through better implementation of existing technologies and
guidelines for the prevention, management and treatment of kidney disease.
Across the health and care system, a national effort should be made to
improve uptake of these interventions.

Paediatric kidney disease is relatively rare and historically has not received the
attention it deserves. Establishing some oversight of paediatric kidney care from
kidney policymakers, in particular to establish better transition management for
young adults, has been highlighted by stakeholders as important.

The population with chronic kidney disease and end-stage kidney disease is
varied in terms of age, gender, ethnicity and the root causes of illness, and
therefore the same diagnostic techniques, management strategies and
treatments are not effective for all groups. For example, eGFR tests have
been shown to be less sensitive at predicting outcomes in people who are of
South Asian descent. There should be efforts made to personalise the care of
patients with, or at risk of, kidney disease across the disease pathway. These
should include:
• Use of the best possible diagnostic tests based on proven effectiveness
for the demographics of the specific patient
• Genetic testing followed by appropriate management for those at risk of
inherited kidney disease
• Patient choice in treatment, e.g. support with home dialysis for patients
who feel this would better enable them to continue working and
undertaking their usual activities
• Access to new and proven therapies to manage and slow disease
progression in a timely manner
• Creating an environment fostering innovation and its implementation in
real-world settings

Kidney disease is complex and is intertwined with other chronic/serious health

conditions. The NHS and voluntary sector organisations should seek to break
down silos between organisations and teams working on kidney disease and
related conditions such as diabetes, hypertension, cardiovascular disease and
inherited genetic conditions.

Modelling suggests that more proactive engagement with people who are at
risk or have kidney disease would be clinically and cost effective, e.g.:
• Peer engagement to improve adherence to disease management strategies
• Engaging in proactive discussions around living donor transplants
• Community outreach to engage underserved groups

22
However, given the frequent multi-morbidity of people with kidney disease,
this engagement could be even more cost effective if it addressed multiple
health conditions relevant to these populations at the same time. The NHS and
voluntary sector should consider how to pool resources and efforts to collaborate
across multiple programmes of engagement.

Current research funding for kidney disease is just 1.4% of relevant healthcare
budgets, while kidney disease represents 3.2% of NHS budgets, with a risk of
significant growth in this burden. Kidney disease research funding should be
increased in line with the clinical and financial burden of disease.

Clinical
In this report, kidney disease has been referred to as a silent killer, because
many patients are undiagnosed or asymptomatic until they reach a later stage
of disease. Stakeholder interviews have revealed opportunities to improve
adherence to best practice guidelines by making them simpler and more
accessible, especially for primary care, where the huge breadth of conditions
general practitioners treat is a challenge. In addition, measures should be taken
to monitor local adherence to guidelines and intervene where necessary.

To address barriers to implementation, focus is required on how best to provide

knowledge transfer and pathway/process development. This could include
closer collaboration between secondary and primary care, e.g. with regular
virtual consultations between general practitioners and kidney specialists.

A broader transformation of renal services is needed to improve care through

standardisation and knowledge sharing. In England, the Renal Services
Transformation Programme (RSTP) is currently reviewing adult renal services
and recommending areas where improvements should be made. The
recommendations for service improvement in the areas of early detection,
dialysis and transplantation are in alignment with the findings of this report,
which also addresses the scale of the challenge across the whole of the UK
and the requirements of paediatric services to meet future needs.

Severe kidney disease in children can have a similar impact in terms of

mortality and lifelong disease to cancer. Because chronic kidney disease is a
lifelong, gradually deteriorating condition, children with mild chronic kidney
disease are likely to develop severe chronic kidney disease later in life, and
therefore early intervention and ongoing management is important. Currently,
however, poor infrastructure exists for children with kidney disease transitioning
to adult services. Until recently, services were overseen nationally by a clinical
reference group that included several other paediatric sub-specialties, which
may be a cause for this disconnect. There is now a separate clinical reference
group in place for paediatric renal services, and one of the focus areas should
be establishing a more effective transition to adult services.

23
Research
In the development of this report, several evidence gaps were identified, and
further research should be considered to address them:
• Understanding the rate at which patients progress through the stages
of chronic kidney disease is essential to predicting future demand for
services. However, much of the data currently in the public domain
is out of date, and up-to-date transition probabilities/relative risks of
progression of chronic kidney disease for the whole population and
subgroups are needed.
• Understanding the relative risk/rate of progression for undiagnosed
populations is essential for assessing the cost effectiveness of early
diagnosis and treatment interventions, but there is very little published
literature relevant to the UK. Studies, potentially using real-world
data, comparing the relative rates of progression in diagnosed vs
undiagnosed populations are required.
• Sources such as the renal registries provide data on the numbers of
patients receiving dialysis. However, there is limited data on unmet need
or delays in meeting need, and as more patients progress to later-stage
kidney disease, having real-time data which allows monitoring of any
potential capacity pressures will become increasingly important.
• This report utilises evidence from other European countries to estimate
the economic burden of kidney disease for the UK. UK-specific studies on
the impact of kidney disease on economic productivity are necessary.
• There is evidence of a strong and complex relationship between kidney
disease and mental health. UK-specific studies on this relationship, including
the impact of poor mental health on adherence to treatment, are needed.
• The evidence base relating to rare forms of kidney disease is scarce.
Further research in this area is required to understand the natural history,
determinants (including genetic), treatment effectiveness and burden of
rare forms of kidney disease.
• Paediatric kidney disease is relatively rare and often complex. Better
data and evidence are required to understand the needs of these
patients, e.g. studies characterising their epidemiology, demographics
and broader health needs.
• This report has highlighted the multitude of risk factors for kidney disease,
but evidence on the causal link between diabetes, hypertension, chronic
kidney disease and other risk factors at a population level is scarce. Studies
investigating the relationships between these conditions in a predictive
manner would provide a powerful tool for population health planning.
• There are still large evidence gaps on how Covid-19 has affected and
will continue to affect people with or at risk of kidney disease. At the time
of writing this report, work in this area is ongoing using the OpenSAFELY
platform, and it is important that it continues to be supported.
• There is an opportunity for the four nations of the UK to learn from each
other on the management of kidney disease, but inconsistent data
is a barrier to this. Introducing more consistent data, e.g. extending
the Healthcare England Survey methodology to Scotland, Wales and
Northern Ireland, could be an important enabler for driving better health
outcomes for the entire UK population.

24
Background
Introduction: kidney disease, the silent crisis

The kidneys are vital, life-sustaining organs, whose primary function is to filter the
blood to remove wastes, poisons and excess fluid from the body.1 The kidneys
are located just below the rib cage, one on each side of the spine.2 Each kidney
is made up of units called nephrons, and their function is to remove waste
while returning needed components back into the blood.2 The kidneys are also
responsible for controlling blood pressure, stimulating red blood cell production,
keeping bones healthy, regulating blood chemicals and secreting essential
hormones.1, 2 When the kidneys are not working properly, harmful toxins and
excess fluids build up in the body, which may lead to kidney failure.3 These
symptoms can include extreme tiredness or lethargy, persistent headaches,
swelling in the face and ankles, fluid retention, lower back pain and death.1

The term kidney disease encompasses a broad range of conditions that lead
to issues with kidney function.1, 2 Since the kidneys are vital to many bodily
functions, kidney disease increases the risk of developing other diseases, and,
conversely, other diseases are risk factors for kidney disease.1, 2 There is no cure
for the majority of kidney diseases, and managing them is a complex task as
kidney abnormalities exist across every age group, gender and ethnicity and
can occur without any warning, often without symptoms.1, 2

Persistent and progressive damage to the kidneys leads to chronic kidney

disease (CKD).4 CKD is a major public health issue. It affects 13% of the global
population and is predicted to be the fifth leading cause of life years lost
(LYL)* worldwide by the year 2040.5, 6 In 2016, the UK prevalence of all-stage
CKD was estimated at 12.7% of the adult (16+) population, and 5.1% of the
population had CKD stages 3-5.7 This data was based on a comprehensive
population survey of the UK and includes both diagnosed and undiagnosed
kidney diseases in the population.7

CKD is defined as abnormalities of either the kidney structure or its function

that are present for more than 3 months. CKD is a long-term condition in which
kidney function declines over time,1 and it is grouped and characterised into
five stages (Table 1), each of which is associated with progressive damage.8
As CKD stages 1-2 are not well diagnosed or reported, the majority of patients
are diagnosed between stages 3 and 5; however, there are many variables
and risk factors that influence diagnosis, including age, gender, ethnicity and
co-morbidities (e.g. diabetes, hypertension, and cardiovascular disease).5

* Life years lost is a measure of premature mortality which takes into account frequency of death and age at
which it occurs. LYL is calculated by multiplying the number of deaths by a global standard life expectancy at
which death occurs.

25
Table 1. Stages of chronic kidney disease

Stages of chronic % of kidney

Symptom/implication
kidney disease function

Kidney damage
STAGE 1 with normal
kidney function • People in early-stage CKD may not
100-90%
know they have CKD as they often feel
Kidney damage well and show no symptoms
STAGE 2 with mild loss of
kidney function
89-60%

Mild to moderate
STAGE 3a loss of kidney
function
59-45%
• People are often diagnosed with kidney
Moderate to disease in the mid-stage, with many
STAGE 3b severe loss of people still asymptomatic as waste in
kidney function 44-30% the body builds and blood pressure rises

Severe loss of
STAGE 4
kidney function
29-15%

• Patients with kidney failure require dialysis*

or a kidney transplant to stay alive
• A proportion of people with kidney
STAGE 5 Kidney failure failure will not receive either dialysis
Less than 15% or transplant, instead undergoing
conservative care

*Dialysis is a type of kidney replacementtherapy that replaces the blood-filtering function ofthe kidneys.
In early-stage CKD (stages 1-2), patients are often asymptomatic, but as
the stage of CKD increases, non-specific symptoms develop and include
tiredness, nausea, sleep disturbance, more frequent urination (including at
night) and muscle cramps. When kidney disease is advanced (CKD stage 5)
and kidney function is less than 15%, typically patients rely on dialysis or kidney
transplantation where appropriate. Untreated kidney failure is fatal.8

26
Detection and diagnosis of CKD is a challenge. A 2020 study9 estimated
that approximately half of people with CKD were undiagnosed. Most people
with CKD are typically asymptomatic in the early and late stages and only
diagnosed as a result of routine blood or urine tests, including those for other
conditions,10, 11 or once the disease has progressed. Uncoded CKD, where the
disease is not formally diagnosed, is associated with lower quality of care, as
well as greater numbers of co-morbidities and adverse outcomes.12

These estimates, from 2016, are likely to significantly underestimate the current
and future burden of CKD, since the prevalence of CKD was much higher in
the older population, e.g. the all-stage CKD rate was 46% for the population
aged 75 years or older.7 This means that as the UK’s population is ageing, the
prevalence of CKD is also increasing. Estimates of current prevalence along
with projections to 2033 are provided later in this report.

These dual challenges of increasing prevalence and low detection are the
reason kidney disease can be considered a silent crisis.

Without detection and treatment, kidney disease progresses more rapidly to

end stage (ESKD), at which point the burden on the individual, the National
Health Service (NHS) and the UK economy increases significantly. When on
haemodialysis, patients will spend several hours a week receiving treatment,
preventing them from participating in their usual activities and reducing
their ability to work. A year of in-centre haemodialysis has previously been
estimated to cost the NHS approximately £30,000 per patient.13

Productivity losses due to dialysis are not well characterised in the UK, but
assuming similar losses to those observed in other European countries,
patients and the people who support them will on average lose 20 days of
work per year, an estimated cost to the economy of £2,940 per person per
year.14 This average is relatively low, since most patients on dialysis are of
retirement age,13 although there are some dialysis patients of working age (55
years and younger), in particular many using home dialysis. Assuming similar
losses to other European countries, employed people on dialysis on average
will miss 30 days of work due to absenteeism and will lose an additional
56 days of work due to presenteeism (showing up to work but lacking
productivity due to illness).14 In total, the productivity loss per annum for an
employed person on dialysis is estimated to cost the economy approximately
£12,600,14 and many people on dialysis are unable to work at all. A Dutch
study estimated that only 20% of people on dialysis were in full employment.14
In addition, a person caring for a loved one on dialysis provides on average
9 hours of informal care per week, equivalent to an additional £9,200 in lost
productivity per year.14

27
Kidney disease policy and research

Despite its high prevalence and burden, kidney disease has not received the
same level of priority as other long-term conditions. The 2019 NHS Long Term
Plan called out the need for better care of other major health conditions such as
cardiovascular disease, diabetes and stroke but was silent on kidney disease.15

Paediatric kidney disease populations are often neglected from a policy

perspective due to small patient numbers and the complexity of the disease in
children, since they do not fall under the same national leadership structures
as the adult population with kidney disease. This can result in a lack of focus
and structure, in which case, some challenges surrounding the paediatric
kidney population might not be clearly understood.16

The last significant review describing the burden of kidney disease in the UK
(which focused on England) was published in 2012. This review was focused
on estimates based on 2010 NHS data.17 The financial burden of CKD and
ESKD estimated by that report was £1.45bn (1.3% of NHS budgets) and is still
used in policy documents despite the increasing prevalence of CKD due to
the ageing population, the impact of additional risk factors and increasing
costs to the NHS.17-19

Research funding for kidney disease is also disproportionately low compared

with the current economic burden. As set out below (Table 2), kidney disease
received only 1.4% of relevant public sector research budgets in 2021-2022, in
line with the cost to the NHS of CKD in 2010, but likely far below the equivalent
share of the current economic burden of kidney disease in 2023, estimated at
3.2% of the total NHS budget in this report.
Table 2. NHS funding and research cost for kidney disease

NIHR spent
Total
UKRI/ UKRI research
NIHR Total KD estimated
MRC Medical programmes KD %
funding research relevant
Year funding research Budget 2022 of
for KD funding research
for KD budget (excluding budget
(£m) (£m) budget
(£m) (£m) Covid-19)
(£m)
(£m)

19/20 7.7 14 21.7 800 426 1,226 1.8

20/21 7.8 8 15.8 800 426 1,226 1.3

21/22 6.7 11 17.7 800 426 1,226 1.4

28
Scope of this report

The purpose of this report is to consolidate and build on the existing evidence
regarding the burden of kidney disease in the UK. It has a broader scope than
the 2012 report, as it covers multiple types of kidney disease:
• CKD
• Acute kidney injury (AKI)
• ESKD
• Rare kidney diseases
• Paediatric kidney disease

It also takes a broader perspective on economic burden, measuring this in

terms of both cost to the NHS and cost to the wider economy. The following
sections of this report cover:
• A more detailed overview of each group of patients with kidney disease
• Risk factors and inequalities
• The epidemiology (incidence and prevalence) of kidney disease in the
UK, now and projected to 2033
• The economic burden of kidney disease, for both the NHS and the wider
economy, now and projected to 2033
• Interventions to reduce this burden, with a focus on CKD
• Recommendations

29
Overview of kidney disease
Chronic kidney disease

CKD is a progressive condition and is usually asymptomatic in the early stages.

For kidney disease to be considered chronic, damage must be evident for at
least 3 months.20 As the disease progresses, the kidneys become increasingly
damaged, leading to a range of symptoms such as fatigue, weakness, difficulty
concentrating and loss of appetite. In advanced stages of CKD, patients may
experience serious complications such as high blood pressure, anaemia, bone
disease, and increased risk of cardiovascular disease (CVD). Over time, CKD can
cause renal dysfunction and progression to ESKD.21

Detection and diagnosis of CKD at early stages is crucial, as the right treatment
can slow disease progression and prevent complications. CKD stages are
traditionally categorised based on estimated glomerular filtration rate (eGFR;
G categories, G1-G5), which is a measure of how well the kidneys filter the
blood. The risk of progression is assessed based on a combination of eGFR
and presence of the protein albumin (albuminuria; A categories, A1-A3).20 As
per the table below (Table 3)8, risk level is scored between 1 and 4+, and this
score helps determine the method and intensity of monitoring and treatment
of patients. As these scores increase, so does the risk of CKD progression,
death from all causes, cardiovascular death and AKI.20

30
Table 3. Guide to frequency of monitoring (number of times per year) by eGFR and albuminuria

Persistent albuminuria categories

description and range

A1 A2 A3

Normal to Moderately Severely

mildly increased increased

<30 mg/g 30-300 mg/g >300 mg/g

<3 mg/mmol 3-30 mg/mmol >30 mg/mmol

Normal
G1 to mildly ≥90 1 if CKD 1 2
increased

Mildly
G2 60-89 1 if CKD 1 2
decreased

Mildly to
G3a moderately 45-59 1 2 3
GFR decreased
categories
(ml/min
per 1.73m2)
description Moderately
and range G3b to severely 30-44 2 3 3
decreased

Severely
G4 15-29 3 3 4+
decreased

Kidney
G5 ‹15 4+ 4+ 4+
failure

GFR and albuminuria grid to reflect the risk of progression by intensity of colouring
(green=low risk, yellow=moderate risk, orange=high risk, pink and red = very high risk.)

31
As CKD is a long-term condition, management of kidney disease relies on treatment
to prevent CKD progression and avoidance of risk factors such as smoking,
diabetes, hypertension and CVD.3 It is important for a patient to be properly staged
in order to carry out accurate assessments of the severity of the disease, which helps
to inform decisions associated with their management and monitoring.3 Since there
is an association between CKD and increased risk of CVD, well-managed patients
can reduce the risk of disease progression by monitoring their eGFR and associated
risk factors such as cardiovascular events, hospitalisation and blood sugar, as these
risk factors are associated with poor outcomes.22

In the UK, managing CKD prior to ESKD primarily involves the use of medications
to control blood pressure and glucose levels, medications to manage CKD
complications (e.g. metabolic bone disease anaemia, etc) and lifestyle changes
such as dietary adjustments and exercise.21 While effective medications such
as angiotensin-converting enzyme inhibitors (ACEs) and angiotensin receptor
blockers (ARBs) have been available since the 1980s, there is evidence that not
all patients who could be receiving them, based on the National Institute for
Health and Care Excellence (NICE) guidelines, are receiving them.16, 23-25 Absence
of treatment can lead to faster progression to ESKD, along with increased risk of
cardiovascular events such as heart attack and stroke.26

Sodium-glucose transport protein 2 (SGLT-2) inhibitors are also known to slow

progression towards ESKD and reduce the risk of cardiovascular events.27 These
medicines have been available for patients with conditions such as diabetes since
2013, and NICE has now approved the use of SGLT-2 inhibitors for CKD.24 Given these
treatments are new to CKD, NICE estimates that approximately 19% of patients with
CKD will be eligible. In England, this is equivalent to about 340,000 people.24

Acute kidney injury

AKI is a common health problem,28 typically occurring in patients who are

hospitalised, especially those who require treatment in an intensive care unit
(ICU).29 AKI is characterised by an abrupt loss of kidney function and is strongly
associated with high morbidity and mortality.30 AKI is complex due to multiple
risk factors, including age, heart failure, liver failure, CKD, anaemia and exposure
to nephrotoxic agents such as antibiotics.29 Patients who experience AKI are
at higher risk of developing CKD in the future.31 In one study, CKD developed in
approximately 25% of hospitalised patients with AKI after 3 years.32

AKI is associated with poor patient outcomes, increased length of hospital stay and
high mortality.31 Based on a national study in the UK, up to 30% of deaths attributed
to AKI could have been prevented with early recognition and treatment.31

A significant proportion of patients with AKI require management in a

hospital setting, which involves fluid resuscitation, avoidance of nephrotoxic
medications and correction of electrolyte imbalances.33 Optimal
management of AKI requires close collaboration with a multi-disciplinary team
including primary care physicians, nephrologists, allied health professionals
and other subspecialists participating in the care of the patient.33
32
End-stage kidney disease

In ESKD, permanent kidney damage has occurred to the point where the
kidneys are unable to support life.34 Patients may experience a wide variety of
symptoms, including fatigue, drowsiness, decrease in urination or inability to
urinate, dry skin, itchy skin, headache, weight loss, nausea, bone pain, skin
and nail changes and easy bruising. This stage is ultimately fatal and requires
either dialysis – a kidney replacement therapy that replaces the normal blood
filtering function of the kidneys – or a kidney transplant. Currently, there are
30,000 people in the UK who rely on dialysis to stay alive,34 and every year,
around 3,000 people receive a kidney transplant.35 The number of people
with ESKD requiring kidney replacement therapy (KRT)* has been increasing
worldwide and is predicted to double by 2030.36

Management: dialysis

Two major types of dialysis exist to manage ESKD – haemodialysis and

peritoneal dialysis.37 In the UK, the majority (72%) of the 7,500 adults a year
starting KRT begin with haemodialysis, where an artificial kidney machine
is used to clean the blood.38 The average number of sessions for a patient
on haemodialysis is three times a week, for an average of 4 hours per
session, both at home and in-centre.39 In 2019, cost estimates for in-centre
haemodialysis were approximately £30,000,13 representing a huge cost
burden to the NHS and a huge impact on patients’ lives.34 Beyond allowing
greater flexibility in a patient’s schedule, as they can dialyse overnight, home-
based haemodialysis was significantly cheaper, with an annual estimate
of over £20,000 compared with in-centre dialysis,13 and these more regular
sessions at home can lower restrictions on dietary and fluid consumption.40 In
2020, 1,400 patients were on home-based haemodialysis.34

The second form of dialysis, peritoneal dialysis, uses the lining of the abdomen
(peritoneum) to filter the blood through a daily routine at home.40 Around
3,800 patients in the UK were on peritoneal dialysis in 2020.34 Peritoneal
dialysis is classified into two types: continuous ambulatory peritoneal dialysis,
which uses a portable machine for at least 2 hours a day, and automated
peritoneal dialysis, which uses a home-based machine overnight.40

* Kidney replacement therapy (KRT) is a term used to encompass treatments used for kidney failure.
These treatments include dialysis and transplantation.
33
Management: transplantation

In the UK, over 2,900 adult kidney transplants and 100 paediatric kidney
transplants are performed annually.35 For adult patients waiting for a kidney
transplant, the average time frame is 2-3 years, with about 4,600 active
patients on the waiting list in 2022.35 For patients, the typical time frame from
when they start on dialysis to transplantation is on average 3 years.35 Among
those on the waiting list, some receive a transplant, but others die waiting or
are removed, typically from becoming too unwell for transplantation (Figure
1).35, 41 The majority of adult transplant recipients (>70%) receive deceased
donor kidneys, while the opposite is true for children – the majority (>65%)
receive living donor kidneys.35 Patient survival at 5 years is 88% for adult
patients who received deceased donor kidneys and 94-95% for adult patients
who received living donor kidneys.34, 35 On average, deceased donor kidneys
last 15-20 years, while living donor kidneys last 20-25 years.35

Figure 1. Representation of transplant waiting list over 5-year period

Figure 1. Representation of transplant waiting list over 5-year period

YEAR 1 YEAR 3 YEAR 5

N=4,600 N=2,852 N=627

7% die
2% die 5% die

34% (1,564) 68% (1,939) 78% (489) 8% removed

receive a receive a receive a from waiting list
2% removed 5% removed
transplant from waiting list transplant transplant
from waiting list

Footnote: From years 1-3, 2% (92 people) will be ineligible to receive a kidney and 2% (92 people) will die. From
years 3-5, 5% (143 people) will be ineligible to receive a kidney and 5% (143 people) will die. Following being on a
waiting list for
Footnote: From years51-3,
years, 8% (50
2% (92 people) will people) will
be ineligible to beaineligible
receive kidney and 2%to receive
(92 a die.
people) will kidney and
From years 3-5,7% (44people)
5% (143 people)
will bewill die.to receive a kidney
ineligible
and 5% (143 people) will die. Following being on a waiting list for 5 years, 8% (50 people) will be ineligible to receive a kidney and 7% (44 people) will die.

34
Management: conservative care as an alternative

Conservative care is an important therapeutic option for patients with advanced

kidney disease who believe that the burdens of dialysis are not outweighed by its
potential benefits.42 Individuals who neither plan for nor initiate KRT when they
reach kidney failure receive conservative kidney management.42

Conservative care is an option patients may choose over dialysis, with the
objectives including slowing down the progression of kidney dysfunction and
treating complications (anaemia, bone diseases, cardiovascular diseases).43
While there are noted survival benefits of dialysis, many patients are willing to forgo
lengthy hospital stays and dialysis as it means a better quality of life for them;43-46
however, it may also be a precursor to KRT.43 This may be particularly appropriate
for patients in circumstances where they may not increase their life expectancy by
receiving dialysis in any case, e.g. where they have substantial co-morbidities.

Because conservative care is more focused on maintaining remaining kidney

function and preventing or treating symptoms, cost to the NHS is substantially
lower than dialysis (on average £5,600 for conservative care compared to the
£15,000+ for dialysis).43

Conservative care can also be less burdensome than dialysis for carers. When
looking at the carer experience and caregiver quality of life (QoL), carers for
patients on conservative care rate their experience higher than those caring
for patients on dialysis (15 points higher on a 100-point scale). QoL is a concept
which aims to capture the well-being, whether of a population or individual,
regarding both positive and negative elements. For example, common facets
of QoL include personal health (physical, mental, and spiritual), relationships,
education status, work environment, social status, wealth, a sense of security
and safety, freedom, autonomy in decision-making, social-belonging, and their
physical surroundings.47 Fatigue and mental health scores were worse for dialysis
carers than conservative carers, but both had low scores for “assistance from
organisations and government.”48

35
Rare kidney diseases

Rare kidney diseases encompass at least 150 different conditions, most of

which are inherited.49 Although individual rare kidney diseases raise specific
issues, as a group these rare diseases can present challenges in differential
diagnosis, which include small numbers of affected patients, unidentified
causes of disease, lack of biomarkers for monitoring disease progression, and
need for complex care.50 Patients often spend years visiting multiple healthcare
providers before receiving an accurate diagnosis.50 In the UK, according to the
UK Kidney Association (UKKA) there are 20 rare renal conditions that are well
characterised and diagnosed (Table 4).51
Table 4. Top 20 rare kidney conditions in the UK

Rare kidney condition Disease description

• Alport syndrome is a genetic condition that occurs due to an

abnormality in part of the kidneys’ filtering system and affects
around 1 in 5,000 people
Alport Syndrome • Diagnosed by a kidney biopsy and genetic testing
• Blood pressure medication can help maintain kidney
function, although dialysis and/or transplant may eventually
be needed

• aHUS occurs due to an abnormality in the immune

system, with about 20 new cases a year in the UK
Atypical Haemolytic • Symptoms include tiredness, breathlessness and feeling
Uraemic Syndrome extremely unwell
(aHUS) • aHUS is diagnosed via a blood test
• Treatment may include an infusion of a medication called
eculizumab

• ADPKD is a genetic condition that causes cysts in the kidneys

and affects around 1 in 2,000 people (equally common in
men and women)
• Common symptoms include high blood pressure and
Autosomal dominant
urinary tract infections (UTIs)
polycystic kidney
• Diagnosed in adulthood by a scan (ultrasound, computed
disease (ADPKD)
tomography or magnetic resonance imaging)
• Blood pressure medication can help maintain kidney
function, although dialysis and/or transplant may
eventually be needed

36
Rare kidney condition Disease description

• ARPKD is a severe genetic condition causing cysts in the

kidneys affecting around 1 in 20,000 people (equally
common in boys and girls)
Autosomal recessive
• The main symptom is large kidneys
polycystic kidney
• Diagnosed by an ultrasound scan during pregnancy
disease (ARPKD)
• By the age of ten, most children with ARPKD will have
developed kidney failure and need dialysis or a kidney
transplant

• Bartter syndromes are very rare types of inherited kidney

conditions that cause excess salts and water to be lost
from the body in the urine, affecting around 1 in 1 million
people (boys and girls are affected equally)
Bartter syndrome • Symptoms include vomiting, muscle weakness, persistent
thirst and a general failure to thrive in children
• Diagnosed in childhood by blood tests
• Treatment focuses on ‘topping up’ the levels of potassium,
magnesium and salt by dietary changes and supplements

• C3G occurs due to immune system dysfunction and

affects around 1 in 500,000 people (men and women are
affected equally)
• Symptoms include blood and protein in the urine
C3 glomerulopathy
• Diagnosed by kidney biopsy
(C3G)
• Dietary changes, immunosuppressant drugs and blood
pressure medication can help with kidney function,
although dialysis and/or transplantation may eventually
be needed

• Cystinosis is a rare inherited condition caused by a build-

up of an amino acid called cystine; it affects 1 in 200,000
people (equally common in men and women)
Cystinosis • Symptoms include difficulty feeding, increased thirst, slow
growth and muscle weakness
• Diagnosed in early childhood by a blood test
• Cysteamine is used to control the build-up of cystine

• Cystinuria is an inherited condition that causes an amino

acid called cystine to build up in the urine and form
crystals, which can eventually turn into kidney stones, and
Cystinuria affects around 1 in 10,000 people
• Symptoms include lower back or groin pain and UTIs
• Treatment aims to keep the urine diluted to prevent stones
from forming

37
Rare kidney condition Disease description

• DDD occurs when part of the immune system called

complement is deposited in the kidneys and affects 1 in
500,000 people (men and women are affected equally)
• Symptoms include blood and protein in the urine, swelling
Dense deposit disease around the eyes and ankles and high blood pressure
(DDD) • The precise diagnosis depends on the appearance of the
kidneys by biopsy
• Dietary changes, immunosuppressants and blood pressure
medication can help with kidney function, although dialysis
and/or transplant may eventually be needed

• Gitelman syndrome is a rare inherited condition that

causes salt to be lost from the kidneys in the urine and that
affects around 1 in 40,000 people (men and women are
affected equally)
Gitelman Syndrome • Symptoms include extreme tiredness, muscle cramps,
cravings for salty food and excessive thirst
• Diagnosed by blood tests
• Treatment focuses on ‘topping up’ the levels of potassium,
magnesium and salt by dietary changes and supplements

• IgAN occurs when immunoglobulin A damages the

kidneys, reducing their ability to clear waste from the
body; it affects around 1 in 50,000 people (men are more
IgA nephropathy likely to be affected)
(IgAN) • Some people with IgAN do not have any symptoms
• Diagnosed in late teens to early adulthood by a kidney biopsy
• Blood pressure medication and/or immunosuppressants such
as steroids may be prescribed to help the immune system

• Lowe syndrome is a very rare genetic condition that causes

severe physical and cognitive disabilities; it affects around
1 in 500,000 people (only affects boys)
Lowe Syndrome
• All babies with Lowe syndrome have cataracts over their eyes
• Diagnosed shortly after birth
• Treatment focuses on symptom management

• MN occurs when the immune system causes the tiny filters

in the kidney to malfunction; it affects around 1 in 100,000
people (twice as common in men than women)
• Symptoms include foamy, frothy urine (like the head on a
Membranous
pint of beer), high blood pressure, puffiness around the
Nephropathy (MN)
eyes and swollen ankles
• Diagnosed between the ages of 40 and 70 by a kidney biopsy
• Around one in three people with MN recover without the
need for any treatment

38
Rare kidney condition Disease description

• MPGN occurs when antibodies are deposited in the

kidneys, affecting 1 in 100,000 people (men and women
are affected equally)
• Common symptoms include blood and protein in the
Membranoproliferative
urine, swelling around the eyes and ankles, high blood
glomerulonephritis
pressure, hives and anaemia
(MPGN)
• Diagnosed by a kidney biopsy
• Dietary changes, immunosuppressants, and blood pressure
medication can help with kidney function, although dialysis
and/or transplant may be needed

• NPHP is an inherited condition that affects the cilia,

affecting 1 in 75,000 people
• Symptoms include excessive thirst, repeated urination,
anaemia, high blood pressure and reduced growth
Nephronophthisis
• Diagnosed in babies and young children by an ultrasound scan
(NPHP)
• Regular blood and urine tests are needed to monitor kidney
function, along with dietary changes, immunosuppressants
and blood pressure medication, although dialysis and/or
transplant may eventually be needed

• PH is a genetic condition where excess oxalate is excreted

by the kidneys. This can lead to kidney stones, affecting 1 in 1
million people (men and women are affected equally)
• Symptoms include blood in the urine, reduced growth,
Primary Hyperoxaluria
anaemia and severe pain in the stomach or back
(PH, also known as
• Diagnosis is often delayed as the condition is so rare. Genetic
Oxalosis)
testing is available in the UK to identify some types of PH
• Treatment aims to keep the urine diluted to prevent stones
from forming. PH can eventually lead to kidney failure and
the need for dialysis and/or transplant

• SRNS occurs when the tiny filters in the kidney are

damaged, causing them to leak protein and retain excess
water, affecting 1 in 30,000 people
Steroid Resistant • Symptoms include protein in the urine, swelling around the
Nephrotic Syndrome eyes and ankles, increased risk of infection, anaemia and
(SRNS) low blood pressure
• Diagnosed in childhood by a blood or urine test
• The first course of treatment is usually steroids which are
effective in the majority of people

39
Rare kidney condition Disease description

• SSNS occurs when the tiny filters in the kidney are damaged,
causing them to leak protein and retain excess water,
affecting around 1 in 30,000 people
Steroid Sensitive • Symptoms include protein in the urine, swelling around the
Nephrotic Syndrome eyes and ankles, increased risk of infection, anaemia and low
(SSNS) blood pressure
• Diagnosed in childhood by a blood or urine test
• The first course of treatment is usually steroids, which are
effective, but the condition may reoccur

• TSC is a genetic condition that causes non-cancerous growths

in various parts of the body, including the brain and kidneys,
affecting between 4,000 and 11,000 people in the UK
Tuberous Sclerosis • Symptoms include epilepsy, autism and learning and/or
(TSC) behavioural difficulties
• Diagnosis is by physical examination and imaging scans
• Medication is prescribed to reduce blood pressure and for
epilepsy

• Vasculitis is an immune system disorder that causes an

inflammation of the blood vessels, affecting 2,000 people
a year
Vasculitis • Symptoms include muscle weakness, tiredness, joint pains
and rashes
• Some types of vasculitis do not need any treatment as the
symptoms resolve over time by themselves

40
Paediatric kidney disease

Although relatively uncommon in children, kidney disease can be a devastating

illness with many long-term consequences, including reduced life expectancy.
Kidney disease in children can be caused by birth defects, hereditary diseases,
infection and systemic disease.52-56 Alongside CKD disease complications seen
at any age, such as anaemia, high blood pressure and mineral bone disorder,
CKD can affect growth in children. Beyond clinical complications, children with
advanced CKD lose many hours of education through hospital attendances
and illness and have a greater incidence of problems relating to behaviour,
relationships and self-esteem.57

Treatment decisions can be complicated by the rarity of the paediatric kidney

disease, meaning there are few specialist centres to help manage the complexity
of these diseases in the paediatric patient population. In the UK, there are
approximately 1,000 children living with CKD.58

Management
Managing kidney disease in children is particularly challenging. Developing best
practices for the management of paediatric kidney diseases is complicated due
to a limited number of studies, which are often single centre or reflect a selected
cohort of children with access to specialist care.59 Some children with ESKD may
need dialysis if they present late or are unsuitable for pre-emptive transplantation
for medical or psychosocial reasons, but for virtually all children, the ultimate aim
is kidney transplantation. Children with kidney disease currently have an average
waiting time (including dialysis and suspension) of 2 years for a kidney transplant,
based on children who were first put onto the national kidney transplant waiting
list between April 2015 and March 2019.60

In general, the care of children with kidney disease requires a multidisciplinary

approach to a much greater extent than adult care (Table 5).57, 61

41
Table 5. Support needed for children with CKD

Multidisciplinary
Role
team

• Manage children and young people with chronic and acute

Paediatric
kidney disease, including through provision of dialysis and
nephrologist
kidney transplantation.

• Essential workers that provide support in dealing with the

emotional, practical and financial impacts of kidney disease
for the patient and their family. Social workers understand the
Social workers
difficulties of managing kidney disease in a child, and they
provide resources for patients, carers and family members to
help balance health-related commitments.

• Professional nurses who work with patients with kidney disease

that requires treatment or surgery. They assist in dialysis
Specialist nurses
treatments and often work in a surgical setting with kidney
transplant patients.

• Provide advice on feeding, as well as support for nutritional

Dietitians
and dietary alterations required for certain kidney diseases.

• Professional caregivers who advocate for children and help

Play specialists
them manage painful procedures or a forthcoming operation.

• Licensed professionals who specialise in helping children cope and

Psychologists
adjust to the emotional stresses of living with a kidney disease.

• Provide tools and information that will help young people learn
to take on the responsibility for their own kidney disease and
Youth workers treatment. Help young people develop skills and support them
in building their confidence and self-esteem, which can so
often be a problem.

42
Risk factors
Clinical risk factors for kidney disease

CKD is associated with a range of co-morbid conditions, particularly, diabetes,

hypertension, CVD, and obesity.18, 19 These conditions are closely linked, with
each one contributing to the development and progression of CKD. Risk of
death in people with CKD rises exponentially as kidney function deteriorates,
largely attributable to CVD.62 Some studies have suggested that diabetes
and hypertension are the leading causes of CKD and are risk factors for the
progression of both CKD and CVD.62 Targeting modifiable risk factors can
therefore improve survival and quality of life by reducing CVD in those with CKD
and slowing progression of CKD to ESKD.62

Diabetes

Figure 2. Prevalence of diabetes in the UK (2014-2019)

Figure 2. Prevalence of diabetes in the UK (2014-2019)

3.4M 3,319,266
3.3M 3,222,559
3.2M 3,116,399
3.1M 3,033,529
3.0M 2,913,538
2.9M 2,814,004

2.8M

310K 301,523
300K 295,753
289,040
290K
2,814,004
280K 271,312
270K 259,966
Prevalence of diabetes (patient population)

260K
250K
240K
230K
220K
210K
198,883
200K 191,590
195,693
190K 188,644
177,212 183,348
180K
170K
160K
150K
140K
130K
120K
110K
99,833
100K 96,114
92,480
90K 88,305
81,867 84,836
80K
70K
60K
50K
2014 2015 2016 2017 2018 2019
Year
England Scotland Wales Northern Ireland

43
Type 2 diabetes is a complex chronic condition characterised by increased
blood glucose levels and is associated with vascular complications.18 Diabetes
damages the blood vessels in the kidneys and impairs their function, leading to
the development and progression of CKD.18, 63

Diabetes is also a leading cause of ESKD.18 Almost one in three people who need
dialysis or a transplant have diabetes, and one in five people with diabetes will
need treatment for kidney disease during their lifetime.64 In the UK, the prevalence
of diabetes varies across the four nations, England, Scotland, Wales, and
Northern Ireland over a six year period (Figure 2).65

Management
Early screening and detection is important, as diabetes is a risk factor for
developing CKD and requires early treatment, which can stop or slow disease
progression. SGLT-2 inhibitors are commonly used to treat type 2 diabetes in
patients with CKD, as they have shown positive effects on diabetic kidney disease
in clinical trials.66

Hypertension

Blood pressure is the force of the blood against the walls of blood vessels as the
heart pumps blood around the body. If this pressure becomes too high, patients
typically are diagnosed with high blood pressure, or hypertension. Hypertension
is a major risk factor for the development and progression of CKD, and it is also
a common consequence of CVD, leading towards ESKD.67,68 Hypertension can
damage the blood vessels in the kidneys, leading to reduced blood flow and
impaired kidney function.67

Management
Hypertension in patients with CKD can be managed through a combination
of lifestyle interventions, including diet modification, and pharmacological
interventions.69 Based on NICE guidelines, calcium-channel blockers are
recommended as first-line pharmacological therapy to manage hypertension
and also have a demonstrated effect on reducing proteinuria (protein levels in the
urine), a key component of CKD. ACEs and ARBs are recommended for those with
proteinuria.69 Management and monitoring of blood pressure is important for
reducing CKD progression and cardiovascular events such as heart attack or stroke.

Cardiovascular disease

Cardiovascular disease is a general term for conditions affecting the heart or blood
vessels. CVD is the most common co-morbidity associated with CKD, and it is a
major contributor to morbidity and mortality in patients with CKD.19 Patients with
CKD have an elevated risk for cardiovascular events; 50% of all patients with CKD
stages 4-5 have CVD, and cardiovascular mortality accounts for approximately
40% to 50% of all deaths in patients with advanced CKD (stage 4) as well as ESKD
(stage 5), compared with 26% in controls with normal kidney function.63 People

44
with CKD are at an increased risk of developing CVD, and those with established
CVD are at increased risk of developing CKD.19 The reasons for this overlap are
complex and not fully understood, but it is believed that shared risk factors such as
diabetes, inflammation, oxidative stress and endothelial dysfunction all play a role
in the development and progression of both CKD and CVD.

Management
Control of traditional risk factors, such as diabetes, hypertension and
dyslipidaemia (also known as high cholesterol), is essential to reduce CVD. The
substantial morbidity and mortality from coronary artery disease in patients
with CKD or ESKD make the effective management of CVD critical.70 Risk factors
for CVD and acute cardiovascular events can be managed in patients with
CKD through lifestyle modification and drugs such as ACEs and ARBs.18, 71 SGLT-2
inhibitors have also shown beneficial effects in reducing cardiovascular events
such as heart failure, stroke and heart attack in patients with CKD.26, 71, 72

Multi-morbidity

Patients with kidney disease often have more than one co-morbidity, including
diabetes, arterial hypertension, hyperlipidaemia, anaemia and malnutrition.23
The presence of these co-morbidities can complicate the management of CKD
and make it more difficult to slow or stop the progression of the disease. Patients
with co-morbidities such as CVD, hypertension and diabetes are at increased
risk of AKI, particularly if they have pre-existing CKD..70 The management of AKI
in patients with co-morbidities can be complex, and it requires a coordinated
approach that takes into account the patient’s underlying conditions.73 Treatment
may involve addressing the underlying cause of the AKI, such as dehydration or
medication toxicity, as well as managing the patient’s co-morbidities to prevent
further damage to the kidneys.33, 74 In some cases, patients may require dialysis to
support their kidney function and prevent further complications.

In addition, these co-morbidities can increase the risk of complications such as heart
attack, stroke and infections, particularly in patients with advanced CKD or ESKD.70

Kidney disease and mental health

While a number of other health conditions are risk factors for CKD, long-term
conditions (including CKD) are associated with a greater risk of mental health
problems and cognitive impairment. For example, patients who have both
CKD and diabetes have a two-fold increase in the rate of cognitive disorders when
compared with patients who do not have diabetes or CKD.75-77 Mental health
problems are associated with a much greater cost to the health service.76 For
example, the NHS, in England alone, spends £8-13 billion per annum on co-
morbid mental health problems in patients with chronic disease.76 Those with
long-term conditions are two to three times more likely to experience mental
health problems, which is associated with high socio-economic deprivation.76
Beyond the problems associated with their management, co-morbid mental
health problems are associated with poorer clinical outcomes, a lower quality of
life, and reduced ability to manage physical symptoms.76
45
Kidney disease has a significant negative impact on the quality of life and
mental health of children and young people.78-82 This impact is seen across their
emotional, social, physical and educational well-being and functioning.83-85
Additionally, as in adults, there is evidence that psychosocial issues have a
negative impact on the medical outcomes of children and young people.86,87

Demographic and inequality risk factors

In addition to clinical risk factors, there are environmental and social factors that
contribute to an increased risk of developing CKD and poor CKD outcomes.
These factors include access to care, social inequalities and biological factors;
biological factors include socio-demographic, biological, genetic and cultural
factors.10, 11 Health inequalities make it challenging for people to receive the
medical attention, access to care and support they need.10, 11 In the UK, some
groups are particularly at a disadvantage when it comes to kidney care.10 It is
well established that people from lower socio-economic groups and people
from ethnic minority groups (previously referred to as Black, Asian and minority
ethnic [BAME] in a previous study) are more likely to develop CKD, progress
faster towards kidney failure and die earlier with CKD.10, 11 As the UK population
as a whole grows older, the demographics within it are changing.88 Today,
most ethnic minorities have younger populations than the majority white British
population; however, by 2051, those ethnic groups, particularly, South Asian,
will have the highest proportion of people aged 50 and older, shifting the
demographics and needs of patients.88

Age and frailty

Kidney disease can develop at any time, but older people are at greater risk
due to risk factors that increase with age.58 Based on 2016 data, 12% of adults
aged 65-74 were diagnosed and staged with CKD.7 In the 2016 Health Survey
for England (HSE), 34% of adults aged 75 or older had CKD stages 3-5.7

Frailty, a syndrome of physiological decline, is associated with an increased

vulnerability to adverse health outcomes and annually costs the UK £5.8
billion.89 Patients with CKD are more frail than the general population because
they lose biological reserves and become more vulnerable to conditions such
as inflammation, physical inactivity, reduced energy intake and metabolic
acidosis.89 Estimating frailty prevalence in CKD is challenging because of the
different criteria used in each study.89 There are studies that demonstrate
the association between frailty trajectories and cardiovascular, kidney and
mortality outcomes in CKD,89 showing that frailty is associated with increased
mortality and rate of dialysis in patients and suggesting that patients who are
more frail have an increased rate of requiring dialysis.89

Ethnic inequalities
Individuals of Black and Asian descent are more likely to progress faster
towards kidney failure and are less likely than white people to receive a kidney
transplant.10, 11 These communities are also disproportionately affected by
inequalities in transplant services in the UK, as they are at greater risk of
developing organ failure, are less likely to be organ donors and wait longer
46
for transplants.90 Thirty-five percent of patients waiting for a kidney are from
ethnic minority groups, while only 7.2% of people from these communities are
on the NHS organ donor register.10, 11 Investigating inequalities in kidney care
and their impact on these communities is not only necessary for reducing
inequalities in the UK but also likely to improve the understanding of access to
care barriers for other groups with ESKD globally, as well.91

eGFR is a measure of kidney function and has been used to predict outcomes
with varied success.92 For patients of European descent, eGFR is inversely
related to mortality and CVD but is not a good predictor of outcomes in South
Asians with similar eGFR levels.10, 11 Albumin-to-creatinine ratio (ACR) has been
suggested to be more predictive of outcomes in South Asians than eGFR 92,
as high levels of ACR was correlated with the increased rates of CVD and
cardiovascular death in South Asian ethnic patients.92

Gender inequality
AKI is more common in men than women after accounting for socio-economic
status, ethnicity, alcohol intake and smoking history.93-95 This contrasts with
current guidelines and clinical scoring systems which place a higher risk on
females, mostly based on older, smaller observational studies.93

Economic inequality
Socio-economic deprivation is a measure of individual and area indicators
that may have a direct link to healthcare and outcomes, often correlated
with poor survival outcomes. Patients with CKD who are socio-economically
deprived have faster rates of disease progression, higher risk of CVD and
premature mortality.96 Patients with CKD and an annual income of £12,500
had a two-fold increased risk of having adverse cardiovascular outcomes
compared with patients with CKD who had a higher income.96

Socio-economic deprivation is also associated with an increased length

of time on the transplant waiting list 97, 95 and more limited access to living
donor transplants, leading to higher rates of mortality and long-term kidney
failure.94 Analysis of survival post-transplant also showed that deprivation
was associated with increased mortality at 1 and 5 years post-transplant, and
patients from deprived areas were less likely to have a functioning transplant
at 5 years.97 Patients in the UK living with kidney disease also report that the
cost of living impacts both their physical and mental health.98, 99

Just as economic circumstances can impact kidney disease, living with kidney
disease can negatively impact individuals’ financial wellbeing. Increasing costs
are driving patients to choose between food, electricity and their health.98, 99
Managing kidney health often requires special diets that can increase food
costs, which are further impacted by inflation, and therefore more likely to
affect people from low-income households or who are economically inactive.98
Since CKD is known as a silent disease, most patients only treat symptoms
when they arise and may neglect daily maintenance of risk factors such as
diabetes or hypertension that may prevent progression of kidney disease.16

47
Transport costs can also be a barrier to patients receiving treatment. Recently,
the cost of travel to appointments has been a focus for the NHS, and as of
May 2022, transport eligibility for people on dialysis was confirmed for in-
centre dialysis in England; however, there are variations in policies around the
UK that impact reimbursement of health-associated travel.98

As with other paediatric conditions, kidney disease can create severe financial
hardship for children and their families. Out-of-pocket expenses such as transportation
(travel and parking for appointments), food and drink, and household bills
can all be increased. Additionally, a critically ill child may mean that one or
both parents are unable to work, or are working less to care for the child, putting
a further strain on household finances and impacting the wider UK economy.98

Health literacy
Health literacy is the degree to which individuals have the ability to find,
understand and use information and services to inform health-related
decisions and actions for themselves and others.100, 101 Health literacy, often
associated with other inequalities, can also have an impact on health
outcomes. In the UK, approximately 80% of people did not know the location
or the function of the kidneys.102 More than half believe, incorrectly, that kidney
transplants last a lifetime and are a cure for kidney disease.102 In the general
public, these inaccurate assumptions lead to reduced uptake of prevention
services and adherence to medical advice, which may lead to increased
morbidity and mortality.101 A systematic review found that people with lower
literacy had less appropriate patterns of health service use and were not
always able to secure appropriate treatment.101, 103 When compared with
people with adequate health literacy, people with limited health literacy
generally enter the health system when they are sicker.101 Twenty-five percent of
people with CKD have limited health literacy, and this disproportionally affects
ethnic minorities and other underserved communities.104

Covid-19–associated risk factors

The Covid-19 pandemic had a significant impact on kidney disease, through:

• Creating new incidence of kidney disease
• Disrupting the care of people with existing kidney disease
• Increasing mortality for people with kidney disease
• Delaying/reducing the diagnosis of diabetic kidney disease (due to
testing not taking place)

Kidney disease incidence and Covid-19

Covid-19 patients had a high risk of developing AKI, and those who did were
more likely to become critically ill. Hospitalised patients with Covid-19 had
a one in four chance of developing early AKI and a further 8% chance of
developing late AKI.105-107 Early AKI was defined by Kidney Disease: Improving
Global Outcomes (KDIGO) creatinine criteria within 7 days of admission,
and late AKI was defined as AKI occurring only after day 7.107 The risk factors
for developing AKI during a Covid-19 infection were similar to those for
pre-pandemic AKI, such as diabetes, cardiovascular disease and multi-

48
morbidity. 107, 108 In turn, patients with AKI had an ICU admission rate of 39.4%
as compared to 18.4% for those without AKI.109 In the ICU, AKI and renal
impairment were associated with an increased need of respiratory support
and mechanical ventilation for critical disease.107, 109, 110

Retrospective studies have also associated increased risk of developing AKI

during hospital admission for Covid-19 in ethnic minority groups (previously
referred to as BAME), potentially further demonstrating inequities in those
communities as noted above.105-107 Beyond developing AKI, patients with Asian
ethnicity were found to have a higher rate of persistent AKI or relapsing AKI
while hospitalised.107

The risk of developing CKD was also high in patients hospitalised with Covid-19
particularly if they did not recover kidney function by discharge – 44.8% of
patients who had not recovered kidney function developed CKD, as compared
to 10.1% who had.106

Disruption to kidney services and Covid-19

During the pandemic, the UK was forced to rapidly evolve existing care models in
preparation for significant front-line service pressures,111 and this created a number
of dilemmas, contributing to poor outcomes in patients with kidney disease.112

A suspension of all non-urgent elective surgery to create hospital capacity for

Covid-19–related activity meant most UK transplant centres suspended kidney
transplant activity,111 although there were geographic variations across the UK
based on the availability of ICU capacity and emergency personnel.111

Mortality in Covid-19 patients during the pandemic

Renal impairment in the ICU was correlated with increased requirement of KRT,
which was further associated with increased mortality.110 The mortality rate was
20–30% in kidney transplant recipients during the first wave of the pandemic,
with a reduction in mortality during the second wave113 and a disproportionate
impact on ethnic minority groups and socio-economically disadvantaged
individuals.112 Although living donation came to a nearly complete stop early
on during the pandemic, it has resumed since then but does not appear to
have reached pre-pandemic levels.112

Patients on dialysis were amongst those at highest risk of death, not just
because of the propensity for serious illness but also because of missed
treatments.114 Data from universal screening of a single dialysis unit in the
UK showed that patients experienced a spike in infection following a spike in
infection of health care workers, implying potential transmission from health
care worker to patient.114, 115

Overall, patients with CKD experienced significant excess mortality during the
Covid-19 pandemic.116 A retrospective analysis of data in England found that
there were 34,000 observed excess deaths in the CKD population from March
2020 to March 2021.116

49
Limitations and ongoing research
In the modelling process, significant gaps were found in the evidence
base, specifically the relationship between Covid-19 and kidney disease,
e.g. uncertainties regarding the incidence of Covid-19 infections in the
CKD prevalent population and the impact of Covid-19 on the paediatric
kidney disease population. At the time of writing, there is ongoing research
investigating the impacts of Covid-19 on kidney disease, in particular work
utilising the OpenSAFELY database, which covers the primary care records
of about 24 million patients in England. This data was not included in this
report. A limitation of current research is that it often does not take a systematic
approach (e.g. there is a need to consider patient outcomes, patient
experiences, workforce capacity and capability, as well as inclusion/diversity of
research participation).117

50
Methodology
Overview of approach

The ambitious scope of this report necessitates a multifaceted methodology,

with elements of evidence synthesis and modelling (Figure 3). It has been
underpinned by broad stakeholder engagement from the outset. Early
engagement was undertaken via workshops with expert clinicians, academics,
data experts within the field of kidney disease and patient representatives. A
subset of these stakeholders was subsequently consulted on a regular basis as
part of a project steering group to review and challenge preliminary and final
project outputs, suggest refinements and provide subject matter expertise.
Representatives from industry were also convened to provide insights into
innovations which other stakeholders may not yet be aware of and challenges
they face in bringing them to market. Input from additional experts was sought
where particular gaps or uncertainties in the data emerged.

A targeted literature review (TLR) of economic and epidemiological research

related to kidney disease in the UK was undertaken. It focused on literature
published over the last 5 years, including published systematic literature
reviews (SLRs) and TLRs which summarised older evidence.

Outputs from the TLR were combined with additional data and grey literature,
e.g. from government websites, where required. These were the key inputs to
epidemiological and health economic (cost-effectiveness) modelling.

The epidemiological modelling focused on understanding the current number

of people with CKD, dialysis, transplantation and AKI and the associated costs.
These were projected forward to 2033.

The health economic model focused on the CKD pathway, understanding

the costs and outcomes associated with the current state of clinical care,
and testing the impact and cost-effectiveness of potential interventions
at a population level. Included interventions were chosen based on
recommendations from stakeholders and availability of evidence.

Figure 3. Diagram of flowchartFigure

methodology
3. Diagram of flowchart methodology

STAKEHOLDER TARGETED EPIDEMIOLOGY

1 2 3 4 COST-EFFECTIVENESS
ENGAGEMENT LITERATURE MODELLING MODELLING
REVIEW

SCOPING MEETINGS STEERING GROUP

(December 2022–January 2023) (February–April 2023)

51
The ultimate output metrics of the modelling are prevalence, incidence,
costs, quality-adjusted life years (QALYs)*, deaths and productivity losses
associated with kidney disease in the UK. Not all of these metrics could be
calculated for all types and stages of kidney disease. The availability of outputs
is summarised in the table below (Table 6).

Table 6. Outcomes captured within each health state for CKD

Cost to Cost to the UK

Incidence Prevalence QALYs Deaths
the NHS economy †

CKD 3-5 ✔ ✔ ✔

CKD 1-2 ✔ ✔ ✔

Dialysis ✔ ✔ ✔ ✔ ✔

Transplant ✔ ✔ ✔ ✔ ✔

Paediatric
✔ ✔ ✔ ✔
kidney disease‡

AKI ✔ ✔

Rare/inherited
✔
kidney disease

* Quality-adjusted life years (QALYs) is a commonly used measure in health economic evaluations to quantify
the effect of medical intervention or prevention programme. QALYs are calculated by multiplying the years of
life by the utility value. In a cost-effectiveness exercise, the current standard of care is taken as the baseline, and
QALYs gained from the new intervention or prevention programme are counted in addition.
† Cost to UK inclusive of productivity costs and transport costs.
‡ Paediatric kidney disease outputs only related to transplantation and dialysis in paediatric kidney disease.

52
Detailed method: stakeholder engagement

Stakeholder engagement played a pivotal role in shaping the inputs of this

report and validating the outputs. Given the complexity of kidney disease, it
was essential to engage a range of stakeholders across the care pathway.
The stakeholders helped to shape the areas of focus for the TLR, identifying key
evidence, providing updates on ongoing unpublished research and reviewing
the modelling and report itself (Figure 4).

For the modelling, where published literature did not exist, stakeholders
provided rationale for assumptions based on clinical practice and experience.

Figure 4. Diagram of stakeholder engagement process

Scoping meetings Steering Group

(December 2022 - January 2023) (February - April 2023)

Who: Thirty stakeholders including Who: Ten stakeholders from scoping

patients, senior NHS clinicians and UK meetings including patients, senior NHS
academics. clinicians, and UK academics.

Objectives: Understand the current and Objective: Validate modelling, including

future care of people with kidney diseases, approach, assumptions and outcomes.
identify priority topics for the targeted
literature review, and advise on key
elements for this report.

In total, 30 stakeholders were involved in the project, including senior NHS

clinicians, academic professors, general practitioners, and senior academics
in kidney disease (many of whom were also clinicians), who were consulted on
data availability, modelling assumptions and ongoing research. These included:
• Secondary care nephrology
• Cardio-renal
• Kidney transplantation
• Paediatric nephrology
• Primary care
• Nephrology clinical service directors
• Epidemiologists
• Registry operators (e.g. Scottish Renal Registry, UK Renal Registry and
OpenSAFELY)
• Public health specialists
• Health inequalities specialists
• Patient representatives with kidney disease were also consulted through
this project

53
Stakeholder engagement began with a series of scoping meetings from
December 2022 to January 2023. A smaller steering group of ten with
clinicians, academics and patients met regularly between February 2023 and
April 2023 to guide the project and validate the key findings. With clinicians
and patients, the objectives of these scoping meetings were to understand the
current state and future state of care for people with kidney disease in the UK:
this included probes on clinical guidelines, changing epidemiology and patient
demographics, opportunities for innovation, and evidence gaps which could
be addressed in this report or future research. With academics and data
specialists, the focus was on identifying, interpreting and understanding the
limitations of data sets currently available in the public domain.

Meetings with the steering group focused on refining the modelling approach,
defining the key interventions for the cost-effectiveness model and pressure
testing the outputs contained within this report. In total, the steering group met
three times from February to April 2023. This was supplemented by ad hoc
meetings with individual steering group members.

In addition to the above, on three occasions, the project team met with Kidney
Research UK industry affiliates, life science companies focused on kidney
health to provide their perspectives on advancements in treatments for people
with kidney disease. They also provided insights on research and operational
challenges their organisations faced with regards to their pipeline therapeutics
for kidney disease in the UK.

54
Detailed method: targeted literature review

The TLR was conducted as a comprehensive way to gather the most up-to-
date, publicly available evidence to inform this report. The TLR informed the
content in this report as well as provided evidence for the epidemiology and
cost-effectiveness models.

The TLR search strategy aligned with standards developed by the Centre
of Reviews and Dissemination at the University of York and was based on
predefined reproducible search strings for epidemiology and economic
literature reviews. The stakeholder engagement scoping meetings helped refine
the search string. Search eligibility criteria followed the population, interventions,
comparators, outcomes, timeframe and study design (PICOTS) framework as
per Cochrane guidelines (Appendix A). This search strategy covered AKI, CKD,
ESKD and other rare and inherited kidney diseases. It included epidemiological
evidence from cohort studies, cross-sectional studies and registry studies and
economic evidence that reported cost and resource use.

The search identified approximately 11,000 UK-based articles, published in

the last 5 years, on the epidemiology and economic impact of kidney disease
(Figure 5). Articles were screened in two rounds: first pass title and abstract
review, second pass full text review.

55
Figure 5. Preferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA) flow diagram (search hits and attrition)

Identification of studies via databases and registers Identification of studies via

other methods
Identification

Records identified
through database Duplicate records
searching: removed (n=2,435)
Total records (n=9,481)

Title/abstracts excluded
(n=5,790)
Animal/in vitro (n=90)
Geography (n=817)
Title/abstracts/records Disease (n=921)
screened (n=7,046) Objective (n=2,395)
Review/editorial/SLR (n=585)
Study design (n=961)
Timeframe (n=30)
Records identified from
Screening

grey literature (n=49)

Full-text publications
(reports) excluded (n=857)
Disease (n=46)
Language (n=1)
Full-text publications Objective (n=350)
screened (n=1,256) Review/editorial (n=44)
Study design (n=11)
Geography (n=399)
Animal/in vitro (n=6)

Final inlcluded reports

Included

(n=448)
Economic: 88
Epidemiology: 360

In some cases, additional targeted searches were performed to find model parameters and
other supplementary evidence outside the search parameters. Additional evidence was
provided through stakeholders in the scoping meetings and steering committee meetings.
These additional searches used articles outside of the original search criteria (e.g. articles from
before 2017).

56
Detailed method: epidemiological modelling

The purpose of epidemiological modelling is to understand the historic trends

in prevalence and incidence in the various conditions under the banner of
kidney disease, to calculate estimates of future demand and disease burden.

The approach taken was to analyse several years of historic trends and
changes in patient age demographics to project the burden of CKD stages 3-5,
transplantation, dialysis and AKI from 2023 to 2033. It also examines the
known impact Covid-19 has had on these patient populations from 2020 to
2022 (CKD stages 1-2 were projected using the health economic modelling
approach only, due to constraints of the data, as set out below).

The epidemiological model uses historical incidence rates of dialysis and

transplantation to project rates for 2033. Historical rates have been relatively
flat over the last 10 years, indicating that current capacity for dialysis and
transplantation is most likely maximised. Discussions with stakeholders
have indicated that current needs for dialysis and transplantation are being
met; however, there are ongoing stressors to the health system with staffing
and resource challenges (e.g. nurses and techs take on extra hours to meet
current demand for dialysis or availability of live and deceased donor organs for
transplants). An alternative approach to projecting future demand of dialysis uses
historical transition probabilities to estimate the potential number of people on
dialysis based on disease progression rates (described in greater detail below).

Method for CKD

Stages 3-5
The prevalence of CKD stages 3-5 in the UK was calculated based on the
prevalence reported in the 2016 Health Survey for England (HSE), the most
recent HSE report to examine the prevalence of kidney disease.118 Analysis was
undertaken at a whole UK population level, with population numbers taken
from the 2020 Office for National Statistics (ONS) projection in 2020.119 The
benefit of the HSE is that it is designed to be representative of the whole English
population and used a form of random population sampling. Similar data
was not available for Wales, Scotland and Northern Ireland, necessitating
the assumption that this sample from England is representative of the UK and
applied to the entire UK population.

The patient burden of CKD stages 3-5 was projected forward to 2033 using three
methodologies to arrive at a final base-case projection (Figure 6).

Method 1: The prevalence of CKD stages 3-5 was calculated by applying the
average expected prevalence of CKD stages 3-5 in the over-45 population
(~10.1%) to ONS forecasts of the over-45 population. It should be noted that the
under-45 population had very low recorded prevalence of CKD in the 2016 HSE.

Method 2: The prevalence of CKD stages 3-5 for this projection is based on the
average prevalence recorded in each age cohort in the 2016 HSE (Table 7).118

57
The populations in these age cohorts were projected forward by applying
them to the ONS population forecast for each age group. This approach
is consistent with approaches used by other bodies to project CKD 3-5
prevalence, e.g. UK Health Security Agency (formerly Public Health England).

Method 3: This method uses the output of method 2 but adjusts the projection
for the estimated excess deaths due to Covid-19 in 2020.116 This method
provides the base case presented in this report.

Table 7. Prevalence of CKD stage 3-5 by age group

16-34 35-44 45-54 55-64 65-75 75+

Prevalance
- - 0.7% 2.6% 12.3% 34.1%
of CKD 3-5
For CKD stages 3-5 there was no data available for ages 16-34 and 35-44.

Figure 6. Growth in CKD (stages 3-5) prevalence in the UK

Figure 6. Growth in CKD prevalence in the UK

4.0M

3.9M 3.9M
3.85M
3.8M

3.7M
CKD stage 3-5 population

3.6M

3.5M

3.42M
3.4M

3.3M

3.2M

3.1M

3.0M
2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033
Population growth
Age-adjusted population growth (Covid-19 adjusted)
Age-adjusted population growth (Covid-19 unadjusted)

Additional explanatory variables to account for risk factors other than age were
explored, in particular diabetes. However, it was found that UK studies forecasting
diabetes growth used age-stratified population growth as the basis of their
projections, which is already accounted for in methods 2 and 3 (base case).

58
Stages 1-2
To understand the costs associated with CKD stages 1-2, estimates from the
cost-effectiveness model were used (see methodology for cost-effectiveness
model below). As stages 1-2 are not well diagnosed or reported, insufficient data
prevented forecasting using the epidemiological model methodology. In the cost-
effectiveness model, prevalence of CKD stages 1-2 was estimated through the 2016
HSE and literature. The cost-effectiveness model utilised transition probabilities to
move patients between states. Patients in stages 1-2 can transition to stages 3-5
over time or remain in the same health state.

Method for dialysis

The starting point for modelling of dialysis is current prevalence based on the
2020 UKKA CKD annual report.34 The number of patients on dialysis was projected
forward using the historical compound annual growth rate (CAGR) in dialysis
prevalence from 2015-2019 (pre–Covid-19) and applied to current 2020 figures. As
this projection is based on historical dialysis activity which has stayed relatively flat
over the last 10 years, it implicitly assumes that despite CKD stages 3-5 and ESKD
population growing, the current health system is maximised with limited ability to
accommodate a growth in demand.

The “unconstrained view” of dialysis is an alternative projection of the dialysis

population numbers from the cost-effectiveness Markov model. Growth in the
dialysis population in the unconstrained view is based on historical transition
probabilities of patients in ESKD starting on dialysis. The unconstrained view
represents the predicted need for dialysis taking into account the historical
probability of a patient in ESKD receiving dialysis. It does not account for future
constraints in the delivery of dialysis to a growing ESKD population.

Method for transplantation

The starting incidence of kidney transplantation is based on the number of single-
organ kidney transplants recorded in the NHS Blood and Transplant Reports on Kidney
Transplant.34, 35 The incidence of transplantation has been projected forward using
the historical CAGR in transplant incidence from 2015-2019 (pre–Covid-19) applied
to the most recent data on transplant incidence (December 2021). This projection
is the “constrained view” of transplant and assumes that despite the CKD stage 3-5
population and ESKD population growing, there is limited growth in the supply of living
and deceased donor organs.

The unconstrained view of kidney transplant is an alternative projection of the

incidence of transplant projected in the cost-effectiveness Markov model. Growth
in transplant incidence is based on historical transition probabilities of patients
in ESKD receiving a kidney transplant and demonstrates the “need” for kidney
transplant in the population but does not consider the ability for the healthcare
system to deliver transplants.

Method for paediatric dialysis and transplantation

Paediatric dialysis and transplant populations were derived from UKKA CKD and
NHS Blood and Transplant data, respectively. These populations were projected
forward using the same CAGR methodology as the adult populations. It was
assumed similar costs and productivity losses (for carers) would be incurred to
patients’ families, the NHS and the UK economy in the absence of data specific to
this age group.
59
Method for acute kidney injury
Previous reports have estimated that AKI accounts for approximately 1% of the
NHS budget.120 The approach to estimating the burden of AKI for this report is
to provide a simplified update to these previous studies based on more recent
data. Starting incidence rates were derived from the 2018 UKKA AKI report for
England and ongoing monitoring dashboard of AKI alerts in England.121 Given the
dashboard only reports AKI alerts and not episodes, the number of AKI episodes
was estimated based on the ratio of alerts to episodes from the 2018 report.

Where data was incomplete on AKI alerts, it was assumed that missing data on
AKI episodes would be proportional to recorded episodes within that integrated
care board and quarter. A CAGR was calculated based on the 2016-2019 AKI
alert data, which enabled a projection of AKI forward to 2033 in England. It was
assumed the number of AKI episodes in the UK would be proportional to the
rate of AKI in England as equivalent data was not available for Scotland, Wales
and Northern Ireland. The cost to the NHS of an AKI episode was assumed to be
£5,065. In most cases, AKI may have been part of an admission for a different
primary diagnosis and caused excess bed days; however, for the purposes of this
estimate, each AKI episode was considered as its own admission.

Method for rare/inherited kidney disease

There is limited publicly available information on the epidemiology of rare/
inherited kidney diseases in the UK. The National Registry of Rare Kidney Diseases
is an informed consent register that recruits from a large number of hospitals and
may not be optimal to support the understanding of the epidemiology of rare
kidney diseases. The methodology assumes that a majority of the cost and care
burden of patients with rare/inherited kidney diseases are already captured in
the CKD, transplantation and dialysis modelling.

Detailed method: health economic modelling for CKD (all stages)

A population-level Markov model was used to estimate the current and future
incidence/prevalence and economic burden of CKD across all stages and
show the directional impact of current interventions used based on costs
and outcomes. The model was developed to capture both NHS (direct cost)
and UK economy (wider economic cost) perspectives. The model schematic
was adapted from Wong et al. (2018) to make it possible to explore disease
progression between undiagnosed and diagnosed people with CKD, and this
was the only study identified with a suitable model structure (Figure 7).122 The
schematic was modified to include additional health states for transplantation
(acute event), post-transplant, cardiovascular disease (acute event) and post-
CVD. Based on the availability and quality of data, stages 1 and 2 within the
model were disaggregated, and stages 3a and 3b were combined. Each cycle
length was defined as quarterly (every 3 months) and the time horizon for the
model was set to 10 years.

60
Figure 7. Health economic model schematic
Figure 7. Health economic model schematic

UK population

Undiagnosed Undiagnosed Undiagnosed Undiagnosed Dialysis Post-transplant

CKD 1 CKD 2 CKD 3 CKD 4 care

Mortality

Diagnosed Diagnosed Diagnosed Diagnosed Diagnosed Transplant

CKD 1 CKD 2 CKD 3 CKD 4 CKD 5 (no KRT) (acute event)

Population with CKD – includes both diagnosed and undiagnosed patients

CVD (acute event)*

Post-CVD

*CVD (acute events) are events associated with sudden, reduced blood flow to the heart (e.g., heart attacks and strokes).
*CVD (acute events) are events associated with sudden, reduced blood flow to the heart (e.g., heart attacks and strokes).

The starting point for the model includes adults (18+) in the UK population, with
an average starting age of 49 119 and a CKD prevalent population based on
the same datasets utilised in the epidemiological modelling. People enter the
model at undiagnosed CKD stage 1 based on the estimated incidence rate123 and
can transition to the next stage using transition probabilities. To determine the
probabilities in the diagnosed pathway, values sourced from the literature were
used.124, 125 Based on key opinion leaders (clinicians, data experts, etc) feedback and
external validation, the model assumes that approximately half of the patients in
the diagnosed pathway were appropriately managed by ACEs and ARBs, and
their effects were already accounted for within the probability values.24 Transition
probabilities were adjusted for the undiagnosed pathway based on the relative risk
reduction ACEs and ARBs have on CKD progression in patients with proteinuria.26

In the model, patients can only transition forward or remain in the same state in the
next cycle. Patients who are in undiagnosed CKD 4 transition to diagnosed CKD 4 or
diagnosed CKD 5. Transplantation (acute) and CVD (acute) are tunnel states – all
patients who enter this state transition out in the next cycle. Underlying population
mortality was sourced from life tables.119 CKD-specific mortality rates were calculated
using hazard ratios sourced from literature and applied to the UK life tables.22

Unit costs were sourced from NICE, NHS, UK Personal Social Services Research
Unit (PSSRU) and publicly available literature.14, 24, 126 Costs were adjusted to 2022
sterling using the UK consumer price index for medical/health inflation factor.
Annual or monthly costs were adjusted to be a quarterly cost for inclusion into
the model. A micro-costing approach was not considered as this would not be
generalisable to the whole UK population. Instead, the model leveraged peer-
reviewed literature to source costs.

61
Outputs reported are QALYs, direct costs to the NHS, indirect costs (UK
economy) and total costs. Utility values are sourced from literature.127, 128

A base case provides a snapshot of the current burden of CKD for the adult
population in the UK. The model projects the outcomes and costs of the future
burden of CKD to 2033 with an unconstrained view.

An intervention case estimates the impact of potential interventions on the

base case. Through stakeholder engagement and examination of available
evidence, four interventions were identified with the potential for patient and
system benefits and selected for modelling.

Interventions were modelled by adjusting values such as transition probabilities

and costs used in the base case to quantify the impact of each intervention
individually and combined. The interventions chosen are representative
examples affecting unique sections of the disease pathway (Figure 8). In order
to prevent any confounding effects of combining interventions, the model
assumes that no two interventions will affect the same transition probability or
costs within the pathway. The interventions modelled are:

1. Earlier/improved diagnosis (focused on addressing health inequalities)

2. Improved CKD management (through better adherence to guidelines on
ACEs and ARBs)
3. Use of SGLT-2 inhibitors (to reduce CVD events and progression to ESKD)
4. Increased rate of transplantation (through pre-emptive transplantation)

Figure 8. Health Figure

model to capture
8. Health interventions
model to affecting
capture interventions thethe
affecting disease pathway
disease pathway

UK population

Undiagnosed Undiagnosed Undiagnosed Undiagnosed Dialysis Post-transplant

CKD 1 CKD 2 CKD 3 CKD 4 care

1 Mortality

Diagnosed Diagnosed Diagnosed Diagnosed Diagnosed Transplant

CKD 1 CKD 2 CKD 3 CKD 4 CKD 5 (no KRT) (acute event)
2 3 4
Population with CKD – includes both diagnosed and undiagnosed patients

CVD (acute event)

Post-CVD

1 Earlier/improved diagnosis 2 Improved CKD management 3 SGLT-2 inhibitors 4 Increased rate of transplantation

62
Two additional interventions – CKD prevention and conservative care – were also
considered based on stakeholders’ recommendations and insights but ultimately
were not modelled due to a lack of evidence upon which to base assumptions.

Intervention 1: earlier/improved diagnosis

Based on feedback from stakeholders, earlier and improved diagnosis has been
cited as an important strategy for reducing the economic burden of CKD. Unlike
for other chronic conditions with established screening strategies, there has been
limited consensus by governments and health systems to prioritise early screening
and interventions for CKD.129 The burden of CKD falls disproportionately on people
with lower socio-economic status, as they have a higher prevalence for CKD,
greater difficulty accessing treatment and poorer outcomes.129 Prioritising earlier
and improved CKD diagnosis is a health equity imperative.

Based on clinical stakeholder engagement, the largest gap in early diagnosis

is among Black, Asian and other minority populations. In the economic model,
the targeted population for the intervention was Black and Asian adults aged 65
years and older. The intervention would primarily involve an outreach initiative
(e.g. screening programmes) within the community. An example of a current
outreach initiative is the Scottish peer educator programme, which works with
different faiths from the South Asian community based in either Edinburgh or
Glasgow to discuss and answer questions on kidney health, disease and organ
donation (living or deceased) and educate audiences on new policies related to
kidney disease and treatment.102, 130

Approximately 15% of adults with CKD are from Black and Asian communities,
and 54% of people within those communities are uncoded.12, 34 To model the
intervention, it was assumed that 25% of the uncoded Black and Asian population
were undiagnosed or not receiving the correct treatment. Under the intervention,
they received an earlier diagnosis, which increased the number of people in the
undiagnosed CKD 1, 2 and 3 stages moving into the diagnosed pathway, where they
can be managed through treatment options recommended by NICE. Costs for the
intervention include outreach efforts (£2 million per year fixed cost), cost of the test
and a general practitioner appointment.

Intervention 2: improved CKD management

Optimal CKD management can reduce the progression of CKD to ESKD. Controlling
high blood pressure (hypertension) in people with proteinuria* through the use
of renin-angiotensin system (RAS) antagonists (e.g. ACEs or ARBs) have shown
benefits in reducing cardiovascular events, CKD progression and mortality.131 ACEs
and ARBs are recommended as a first-line (standard of care) therapy option for
people with CKD who have hypertension, diabetes or proteinuria (ACR >30 or
protein-to-creatinine ratio [PCR] >50), which equates to approximately 83.3% of the
CKD population.23, 24 Discussions with clinical stakeholders and additional external
expert validation have revealed that only 53.3% of the eligible CKD population are
receiving the standard care with ACEs or ARBs.24
* Proteinuria is defined as protein in the urine with an ACR level of greater than 30 mg/g.
63
The model assumes that the intervention will proactively identify the
appropriate patients who may be unmanaged or untreated. People who
received the intervention would experience the benefit of reducing CKD
progression to ESKD.26 Costs of the intervention included the annual cost of the
medications and additional testing and monitoring.24

Intervention 3: use of SGLT-2 inhibitors to reduce CVD events and

progression to ESKD

SGLT-2 inhibitors have demonstrated significant benefits and an even greater

benefit in people with proteinuria 24 in delaying progression of kidney disease
and reducing cardiovascular events in people with CKD with or without
diabetes. While SGLT-2 inhibitors have been approved for use in treating
type 2 diabetes since 2013, dapagliflozin was approved in 2022 for use in CKD
patients with or without diabetes.24 These new medications help the kidneys
to lower blood glucose levels by removing glucose in the urine.24 The promising
outcomes from studies involving SGLT-2 inhibitor use in CKD have shown the
importance of incorporating this intervention in cost-effectiveness modelling.

The eligible population to receive this intervention is approximately 18.8%.24 The

modelling assumption is that 100% of the eligible population will receive this
intervention. The benefit of this intervention is applied in the model by slowing
the progression to ESKD and reducing cardiovascular events. Dapagliflozin
is indicated for use in CKD patients in eGFR stage 3. Costs for the intervention
include annual cost of dapagliflozin and additional testing and monitoring.24

Intervention 4: increased rates of transplantation

For patients with advanced kidney disease, transplants have been shown to be
the best form of kidney replacement therapy, as they are associated with lower
costs and better outcomes in the long term.34 Current waiting time for a deceased
donor kidney is 2.5-3 years in the UK. Waiting times for a kidney transplants are
long due to a gap in the supply and demand for kidneys.132 Discussions with
clinical stakeholders have recommended increased rates of transplantation as a
viable intervention to improve clinical outcomes. To demonstrate the benefits of
increasing transplantation rates, one illustrative example identified for the health
economic modelling was pre-emptive transplants.

Pre-emptive transplants before dialysis have several benefits, such as lower risk
of rejection of the donor kidney, improved survival rates, improved quality of life,
lower treatment costs and avoidance of dialysis.133 The benefits of pre-emptive
transplants are particularly significant in children and adolescents with ESKD.133

Currently, only 18% of transplants are pre-emptive.35 To model the benefits of

this intervention, a 100% increase in pre-emptive transplants is assumed, and
this benefit is applied to patients in CKD stage 5 who may be transitioning
to KRT. The cost of this intervention is a fixed cost for outreach within the
community to promote the benefits of pre-emptive transplants.

64
Epidemiology of kidney disease
Prevalence of the various types and stages of kidney disease has grown
considerably in recent years, and will continue to grow, although growth rates
are likely to vary considerably. This is due to the varying risk factors driving growth
(e.g. changing demographics for CKD vs number of acute hospital admissions
for AKI). For dialysis and transplantation prevalence, where actual historic
activity data represent a constrained view showing a system that is most likely at
maximum capacity, scenarios of constrained vs unconstrained demand (e.g.
including potential unmet demand) are provided and vary significantly.

CKD

Factoring in the ageing population and excess deaths in the prevalent

population during the Covid-19 pandemic, an estimated 7.19 million people in
the UK have CKD (all stages) in 2023 – 12.8% of the population aged 16 years
or older (Figure 9). By 2033 this will increase to 7.61 million people. While the
overall prevalence as a proportion of the 16+ population is expected to remain
constant, among the people with CKD, the proportion of later-stage CKD
patients is expected to increase from 45% to 51%. Patients with later-stage CKD
are more likely to be diagnosed; therefore, the recorded prevalence is likely to
increase from the current level.

Figure 9. Epidemiology
Figure 9. Epidemiology of CKD
of CKD stages 1-5stages 1-5
(excluding transplantation and dialysis)
(excluding transplant and dialysis)

2023 3.9M (55%) 3.25M (45%)

2033 3.8M (49%) 3.9M (51%)

0.0 2.0 4.0 6.0 8.0

People living with CKD stages 1-5 (in millions)

CKD 1-2 CKD 3-5

65
CKD stages 3-5
It is estimated that as of 2023, 3.25 million people are living with CKD stages 3-5
in the UK (Figure 10). The prevalence of CKD stages 3-5 is expected to increase to
3.85 million over the next 10 years. This increase is primarily driven by an ageing
population. The ageing population also captures a majority of CKD risk factors
that include diabetes and hypertension.

A study estimated 34,000 excess Covid-19 deaths based on two electronic

medical record databases containing patients with CKD in England.116 After
scaling the estimate to the predicted CKD population in UK in 2020, the Covid-19
pandemic is estimated to have led to an additional 55,000 deaths in people with
CKD in the UK.116 No adjustment has been made for the growth trajectory of the
CKD stage 3-5 population due to Covid-19, as insufficient evidence is available to
make such an assumption at present.

Figure 10. Growth in CKD prevalence in the UK

Figure 10. Growth in CKD prevalence in the UK

4.0M

3.9M 3.9M
3.85M
3.8M

3.7M
CKD stage 3-5 population

3.6M

3.5M

3.42M
3.4M

3.3M

3.2M

3.1M

3.0M
2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033
Population growth
Age-adjusted population growth (Covid-19 adjusted)
Age-adjusted population growth (Covid-19 unadjusted)

The changing age structure of the UK population is the key driver of historic CKD
growth and the projections presented here. Accounting only population growth in
the over-45 population, by 2033, the estimated population of CKD stages 3-5 would
be 3.41 million people (see Method 1 – black line), but anticipated demographic
changes revise this to 3.91 million people by 2033 (see Method 2 – purple line).

The final projection of 3.85 million incorporating Covid-19 excess deaths is the
most likely case based on the evidence available, if risk factors such as diabetes
continue to grow at a faster rate than demographic risk factors.

66
 CKD stages 1-2
Counts for CKD stage 1-2 populations were estimated using the cost-
effectiveness model. Using prevalence estimates from the 2016 HSE as a
starting point, the model predicted that there were approximately 3.9 million
people in CKD stages 1-2 in 2023. At the end of the 10-year time horizon, the
count of patients in CKD stages 1-2 in 2033 declines by 4.6% to 3.8 million.
The decline in CKD stages 1-2 would be driven by the population ageing and
transitioning into CKD stages 3-5.

Dialysis (adult and paediatric)

In 2020, there were 29,354 adults and 226 children and young people
receiving dialysis for ESKD in the UK (Figure 11). If the historic trend in dialysis
numbers, constrained by a maximised health system, continues, then those
needing dialysis will rise to 33,845 adults and 330 children by 2033.

Figure 11. Current and future projections of dialysis in adults with ESKD in the UK
Figure 11. Current and future projections of dialysis in adults with ESKD in the UK
40,000

33,845

35,000

29,354
30,000

25,000
Patient population

20,000

15,000

10,000

5,000

0
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033

Years
Dialysis prevalence historic trend Constrained projection
The alternative approach using historical transition probabilities predicted
that the increasing prevalence of CKD stages 3-5 would exponentially increase
the number of adults needing dialysis for ESKD to 142,920 in 2033 (Figure 12).
When comparing the estimates from the two approaches, there is a significant
gap indicating that the current system does not have capacity to handle the
potential increase in demand. To address this gap, investments should be
made for advanced action to reduce progression to ESKD, and corrective
measures should be taken to address future potential staffing challenges.

67
Figure 12. Constrained vs unconstrained projections of dialysis in adults with ESKD in the UK
Figure 12. Constrained vs unconstrained projections of dialysis in adults with ESKD in the UK
160,000

142,920

140,000

120,000

100,000
Patient population

80,000

60,000

33,845
40,000 30,334
29,354

20,000

0
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033

Years
Historic trend Constrained projection Unconstrained projection

While the Covid-19 pandemic disproportionately increased the risk of

morbidities and mortality among patients on dialysis, current data suggests
that it did not substantially change the total number of people receiving
Figure 13. Adults with ESKD on dialysis
dialysis for ESKD in the UK. (UK population, 2020)

As of 2020, in-centre dialysis was the most 5%

common form of dialysis delivered in the UK
(24,155 adults), followed by peritoneal dialysis 13%
(3,822 adults) and home haemodialysis (1,377
adults) (Figure 13).

Figure 13. Adults with ESKD on dialysis

(UK population, 2020)
82%

In-centre haemodialysis

Peritoneal dialysis

Home dialysis

68
Transplantation (adult and paediatric)

In 2021, there were 2,863 adults and 148 children who received a kidney
transplant in the UK (Figure 14). By 2033, based on current projections and due
to limited availability of kidneys, the number of kidney transplants will rise in
adults and remain about even in children, with 3,615 adults and 135 children
expected to receive a kidney transplant. In 2020, there was a significant drop
in the number of kidney transplants performed, likely due to the Covid-19
pandemic; however, rates of kidney transplants resumed closer towards
historical levels in 2021.

Figure 14. Constrained vs unconstrained projection of adults receiving kidney

transplants in the UK (2033)
Figure 14. Constrained vs unconstrained projection of adults receiving kidney transplants in the UK (2033)

14,000

11,665
12,000

10,000
Patient population

8,000

6,000

3,615
4,000 2,976
2,863

2,000

0
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033

Years
Historic trend Constrained projection Unconstrained projection

If the supply of available kidneys and capacity constraints in NHS services were
not limiting factors, the cost-effectiveness model estimates that 11,665 kidney
transplants would be needed by 2033.

69
Impact of Covid-19: Prior to the Covid-19 pandemic, the increased rate of
transplantation could at least partially be attributed to the opt-out consent
system.35, 41 While the access and rate of transplantation was increasing
prior to the pandemic, there was still a long waiting period for transplant,
averaging around 1.5 years.134 Before 2020, the waiting list size for kidney-only
transplant (excluding multi-organ transplant patients) was on a decline.111 As
the pandemic began, resources were diverted away from non-emergency
medical care and surgeries were delayed when there was a perceived risk for
the patient from Covid-19, which had a dramatic impact on surgeries, such
as kidney transplants. Early models suggested a loss of approximately 1,600
opportunities for adult and paediatric kidney transplants over 6 months due
to the limited transplantation schedule, driving an increase in the waiting list
size.111 The delay in transplantation further compounds the problem of a limited
number of organs, as all deceased organs that could have been utilised are
lost.111 Beyond the waiting list impact, since many patients are on dialysis while
they wait for transplants, the proportion of adults starting dialysis as their first
method of KRT increased from 91.7% to 94.1%.

70
Acute kidney injury

Most cases of AKI involve hospitalisation. The 2018 UKKA report for England
found that 18% of people with an AKI episode died within 30 days of their first
AKI alert.121

In 2022, an estimated 615,000 episodes of AKI occurred in the UK (Figure 15). If

trends in AKI continue, it is projected that by 2033 the number of AKI episodes
will rise by 4% to 637,000.
Figure 15. Current and future projections of AKI episodes in the UK
Figure 15. Current and future projections of AKI episodes in the UK
640,000

636,653
615,550

480,000

320,000

0
2017 2019 2021 2023 2025 2027 2029 2031 2033
Recorded data Projection

71
Paediatric kidney disease

As of 2020, there were 226 children and young people with CKD on dialysis
and a further 148 children who received a kidney transplant. In the 13 British
Association for Paediatric Nephrology (BAPN) centres across the UK, there
were also 619 children and young people living with kidney transplants and
199 CKD children and young people with advanced kidney disease (stage
4 and 5) living without KRT. This is only the population known to paediatric
specialist services. Epidemiological evidence from other countries if applied to
the UK population suggest this could be an underestimate of the true extent of
CKD in children and young people; however, more detailed epidemiological
studies in this population are needed.

Rare kidney disease

In the UK, there are 20 rare kidney conditions that are well characterised
and diagnosed.51 Though individually rare, their collective prevalence is
relatively high (Table 8). The three most common rare diseases are ADPKD,
Alport syndrome and TSC, which have a combined prevalent population of
approximately 58,000. By contrast, among the least common rare kidney
diseases are Bartter syndrome and PH.

Table 8. Estimated prevalence of rare kidney disease in the UK

# Rare kidney disease Estimated UK Prevalence

1 ADPKD 1 in 2,000=33,700
2 Alport syndrome 1 in 5,000=13,466
3 TSC 1 in 6,100-16,750=4,000-11,000
...
19 Bartters Syndrome 1 in 1,000,000=67
20 PH 1 in 1,000,000=67

There is insufficient evidence on the trends in the prevalent population for

these conditions, and as such a projection of future prevalence has not been
possible for this report.

72
The current and future economic
burden of kidney disease
Overview

In 2023, the total cost of kidney disease to the UK economy is estimated

at £7 billion (Figure 16). This includes £6.4 billion in direct costs to the NHS;
approximately 3.2% of the £197 billion total NHS spending across the four
nations. It also includes £372 million productivity loss for people living
with ESKD and the people who care for them, and £225 million in dialysis
transport costs. It does not include non-monetary costs such as the utility of
lost leisure time for patients and carers who do not work, and as such can
be viewed as an underestimate in welfarist* terms.

Assuming that the current capacity for the health system to provide expensive
end-stage kidney care such as dialysis and transplantation remains at
maximum capacity, the cost of kidney disease will rise to £7.8 billion by
2033 (11% increase from 2023), with the biggest increase in cost due to the
increasing prevalence and associated costs of CKD stages 3-5.

However, when modelling unconstrained need using the health economic

model, the 2033 cost could be over £13.9 billion, with the biggest driver being
the growth in demand for dialysis.

It should be noted that the constrained view is likely to be an underestimate,

as a significant unmet need for dialysis and transplantation would likely result
in further complications for patients, with increased costs and mortality either
in the CKD pathway or other parts of the system. Modelling this, however, has
not been possible with the currently available data and evidence.

* Welfare economics seeks to maximise the social welfare or utility across all individuals in society and may include factors not
counted in current NHS Health Technology Assessment evaluation such as leisure or unpaid volunteering time.
73
Figure 16. Economic burden of kidney disease in the UK
Figure 16. Economic burden of kidney disease in the UK

2023

2033 constrained view

2033 unconstrained view

£0 £3.5B £7.0B £10.5B £14.0B

AKI CKD 1-2 CKD 3-5 Transplant

Dialysis Transport Productivity

The economic burden of rare/inherited diseases is excluded from these

estimates due to the epidemiology of these patient populations being poorly
defined. It is anticipated that a majority of these patients’ costs are already
captured in transplantation and dialysis activity costs, which tend to be the
most expensive costs of managing these patients.

Comparison to other research on the cost of CKD

Previous estimates of the economic burden of kidney disease in the UK had

a significantly narrower scope to this report. The most similar in scope was a
2012 report focusing on all-stage CKD based on 2010 data.135 The total burden
of CKD presented in that report was significantly smaller to the estimate
presented in this report for the equivalent conditions and disease stages.
Figure 17 reconciles the key drivers of that difference – both in terms of true
changes to the cost base and methodological differences.

74
Figure 17. Bridge reconciling differences in key drivers of total costs in this
2023 report and the 2012 NHS report
Figure 17. Bridge reconciling differences in key drivers of total costs in this 2023 report and the 2012 NHS report

6B

8B
3B
2B

4B

5B

7B
£-

1B
2023 report (total) £7,016,645,670

Societal costs -£597,142,378

AKI -£3,127,330,925

CKD 1-2 -£167,858,960

Pediatrics -£11,815,706

Inflation -£809,249,402

Incidence/prevalence
-£462,501,460
(dialysis and transplant)

CKD 3-5 -£389,900,379

Anti-hypertensive non-excess -£49,081,001

CVD £173,973,197

Other variation -£125,548,194

Differences in methodology
Additional factors
2012 report (total) £1,450,217,265 Total

75
The cost of CKD

In 2023, CKD stages 1-5 (excluding ESKD treatments like dialysis and
transplantation) will cost the NHS £1.95 billion, with 91% (£1.79 billion) of these
costs attributable to CKD stages 3-5 and 9% (£167 million) attributable to CKD
stages 1-2 based on a cost-per-diagnosed case basis reported in Kent et al.
(2015).126 This alone represents approximately 1% of the total NHS budget.

By 2033, the cost of CKD stages 1-5 is expected to increase by 19% to £2.32 billion
annually. The increase in cost is primarily driven by the increasing prevalence of both CKD
stages 1-2 and CKD stages 3-5 described in the Epidemiology of CKD section and
have not accounted for inflation. These costs are also not inclusive of the KRT costs,
which have been modelled separately, and do not include the cost of innovative
treatments that may become more common in these populations by 2033.

The cost of dialysis

In 2023, the cost of dialysis for people with ESKD is £1.05 billion, or 0.53% of the
NHS budget. A majority of these costs are due to the adult patient population
rather than the paediatric population. In addition to the direct cost of dialysis,
transport for patients on in-centre dialysis costs approximately £225 million
per year. The cost of transport is sometimes incurred by the NHS (e.g. a 2022
study of dialysis in Wales reported that 60% of patients relied on NHS-provided
transport), but for the purposes of this report, the cost of transport is included as a
separate indirect societal cost.

By 2033, based on the constrained model, the cost of dialysis is expected to increase
by 11.5% to £1.16 billion annually, and the cost of transport for dialysis is expected to
increase to £251 million. The increase in cost for dialysis in the constrained model is
due to a modest increase in the ability of the NHS to deliver dialysis to patients with
ESKD and based on the historical CAGR of dialysis from 2015 to 2019 as noted above.

In the unconstrained model, the cost of dialysis is expected to increase by 370% to

£4.91 billion annually and the cost of transport for dialysis is expected to increase
to £1.05 billion annually. The substantial increase in cost is due to the rapid rise in
the population with ESKD who require dialysis in the model. These unconstrained
costs represent the upper bound of the cost of dialysis to the NHS based on the
projected future demand.

The cost of kidney transplantation

In 2023, kidney transplants will cost the UK £293 million. Most of these costs are
attributable to the transplant procedure itself (including hospitalisation, medicines,
etc), while a small proportion of the costs are attributable to care following
transplantation. These costs are also inclusive of the cost of adverse events due
to transplantation and organ rejection. The cost of newer immunosuppression
medicines involved in kidney transplants has not been considered in this report.

76
By 2033, based on the constrained model, the cost of kidney transplants is expected
to increase by 43% to £418 million annually. The increase in cost for transplantation
in the constrained model is due to the increase in the historical CAGR of kidney
transplantation from 2015 to 2019, as noted above, and is contingent on the
availability of organs for transplantation. If organs are not available, it is expected
that patients who would have received kidney transplants would need to undergo
dialysis, which is more expensive per annum and would increase NHS costs further.

In the unconstrained model, the cost of kidney transplants is expected to increase by

105% to £600 million annually. The increase in cost is driven by the increase in people
with ESKD and the historical probability of a patient with ESKD receiving a transplant.

The cost of dialysis and transplantation to the UK economy

In 2023, it is estimated that dialysis and transplantation will cost the UK economy a
further £372 million due to lost patient and carer productivity. By 2033, it is expected
this will increase to £417 million to £2.0 billion in the constrained and unconstrained
models, respectively. These productivity losses already account for many patients
and carers being unemployed due to retirement. As mentioned in the Methods
section, there has been limited research on productivity loss due to dialysis and
kidney transplantation in the UK context, so research from other countries such as
the Netherlands has been relied upon to produce these estimates.

Additionally, it is expected that people with CKD stages 4-5 not on KRT would also
experience some productivity loss; however, these costs have not been included
in the results above. A 2020 study reported that productivity loss in people with
CKD stages 4-5 ranged from £489 to £19,951 per year.127

The cost of AKI

In 2023, AKI will cost the NHS £3.13 billion per year, or approximately 1.6% of the
total NHS budget. This is inclusive of costs due to AKI hospital episodes and post-
AKI discharge care. By 2033, the cost of AKI is expected to increase to £3.24 billion
per year. This increase in costs and AKI cases is based on historical CAGR of AKI
pre–Covid-19 (from 2016 to 2019).

The cost of paediatric kidney diseases

In 2023, dialysis and transplantation for paediatric kidney diseases will cost the NHS
£3.3 million and £8.5 million, respectively. The cost to the UK economy due to lost
carer productivity is £2.7 million, with transport costing a further £1.8 million.

Based on historical CAGR in the paediatric population with ESKD, in 2033, the direct
NHS costs of dialysis and transplantation are expected to increase in the dialysis
population to £11.4 million and slightly decrease in the transplant population to £3.1
million. Productivity loss will increase to £3.4 million, while transport costs will increase
to £2.4 million. The costs presented for paediatrics have already been included in the
costs enumerated in the cost of dialysis and transplantation sections, so they have not
been called out separately to avoid double counting costs.
77
Since the burden of kidney disease for paediatric patients who are not
receiving dialysis or transplantation is poorly defined, the associated costs of
their treatment are not included in these estimates. It is expected that these
patients would contribute additional care costs to the NHS.

The cost of rare kidney diseases

The prognosis of many rare kidney diseases is kidney failure, which ultimately
requires KRT. It is anticipated that for many people living with rare kidney
diseases, the economic burden of kidney disease is primarily driven by the need
for dialysis or transplants. The economic burden of dialysis and transplantation
has already been accounted for in previous sections on the cost of dialysis and
the cost of transplantation. To avoid double-counting costs, costs for rare kidney
diseases have not been enumerated in this section of the report. In addition to
KRT costs, there may be additional resource utilisation for specialised medicines
for rare kidney diseases and additional resource utilisation for those patients in
secondary care services without ESKD. At the time of this report, there is limited
economic literature around the cost of rare kidney diseases in the UK, and this
should be an area of focus for future research.

78
Interventions to manage
the burden of CKD
There is a growing body of evidence that the cost of managing CKD can be
reduced through early detection, pharmacological intervention and outreach.136

A key objective for this report was to assess whether a basket of potential
population-level interventions for managing CKD including ESKD would be
cost-saving or cost-effective. Cost-saving means an intervention reduces
costs of care in addition to benefiting patients clinically. Cost-effective means
that the intervention creates clinical benefits for an additional cost, but that
cost is within a threshold that represents good value (willingness-to-pay
threshold). The most common metric used to evaluate cost-effectiveness is the
incremental cost-effectiveness ratio (ICER), a summary measure representing
the economic value of the intervention compared to the alternative (base
case). The ICER is the ratio of the difference of costs (direct costs) between
the two scenarios to the difference of effectiveness (QALYs). An ICER helps
to determine if the intervention is cost-effective or even cost-saving. In the
UK, NICE determines an intervention as cost-effective if the ICER is below a
threshold range of £20,000-£30,000. A cost-saving intervention has an ICER
of less than 0 when compared to the base case, which means the intervention
has negative net costs and greater benefits.

Through the stakeholder interviews, several interventions were cited as having

the potential to improve clinical outcomes associated with CKD. The following
interventions were applied to the model:

• Early/improved diagnosis: This intervention targets ethnic minority groups

and other underserved populations through outreach programmes to
improve screening opportunities and increase early diagnosis
• Improved CKD management: This intervention targets eligible patients
with chronic kidney disease who are either untreated or not receiving
standard care according to clinical guidelines (e.g. adequate blood
pressure management)
• Use of SGLT-2 inhibitors: This intervention aims to increase uptake of new
medications such as SGLT-2 inhibitors (e.g. dapagliflozin) to reduce CVD
events and slow progression to ESKD
• Increased rates of transplantation: This intervention models the impact
of increased outreach and awareness to increase pre-emptive live donor
transplants. It is illustrative of the benefits of improving transplantation
rates more generally.

To estimate the true impact of the intervention, the interventions were modelled
using the health economics model (cost-effectiveness model) with the
unconstrained perspective, since several of these interventions affect ESKD and KRT.

79
The base case of the model estimated the combined direct costs to the
NHS at £70.7 billion and indirect costs at £20.3 billion (total burden = £91.0
billion) from 2023 to 2033 within the unconstrained perspective. The model
showed that the combined effect of all four interventions generated a cost-
effective ICER of 7,688 and reduced the total burden of CKD by £64.6 million
when compared to the base case. Implementing all four interventions would
increase direct costs to the NHS by £381.1 million; however, the biggest impact
was estimated to be the reduction in indirect costs by £445.7 million. These
cost-savings are primarily driven by the reduction in transportation costs and
lost productivity, as these interventions would reduce the number of patients
receiving dialysis or having a CVD event.

Combined impact

The combined effect of implementing all four interventions is greater than

looking at each intervention individually. The combined interventions had
an ICER of £7,688, which means that as modelled, the combined basket of
interventions was cost-effective (£7,688<£20,000).

As described in greater detail below, when applied to the unconstrained

demand forecast, over the 10 years modelled:
• Collectively, the interventions reduced total deaths by more than 10,000
• Approximately 50,000 QALYs were gained
• They came at a direct cost of approximately £381 million
• These direct costs were more than offset by savings to the UK economy
from increased economic activity and decreased transport costs of
approximately £446 million
• Intervention 4, increased rates of transplantation, was the only
intervention found to be cost-saving as well as clinically beneficial
• Over time, early diagnosis had an increasingly positive impact, and
projecting findings beyond the 10-year time horizon showed that the
early/improved diagnosis intervention would also become cost-saving
by year 13
• For all the interventions, the biggest benefits clinically and in terms of cost
offsets came from reducing the number of patients progressing to dialysis
• When applied to the constrained model, the basket of interventions
is still cost-effective with an ICER of £21,890, which falls within the NICE
threshold range

80
Combined clinical impact
The model estimated that the combined impact of the interventions reduced
deaths by 10,495 over the 10-year period (Table 9). Additionally, 5,465 people
avoided dialysis and over 2,500 people avoided CVD events. The increase in
people with CKD stages 3-5 (3,444,060 vs 3,467,156) and transplants (11,663 vs
11,725) compared to the base case would primarily be driven by interventions 1
and 4, respectively.

Table 9. Clinical impact of combined interventions

Total
Prevalence (year 10) Incidence (year 10)
(years 1-10)

Scenario CKD 1-2 CKD 3-5 Dialysis Transplant CVD Death

Base case 3,742,425 3,444,060 142,918 11,663 192,970

Combined
3,743,058 3,467,156 137,453 11,725 190,448
interventions
Difference 633 23,096 (5,465) 62 (2,522) (10,495)
% change 0.02% 0.7% -3.8% 0.5% -1.3% -0.14%

Combined economic impact

The model estimated that in the base case the cumulative burden of CKD
was £91.0 billion over the 10-year period (Table 10). Implementing all four
interventions would decrease the burden of CKD by £64.6 million (0.07%
difference) and would increase the total QALYs in the population by 49,574.
While direct costs to the NHS would increase by £381.1 million, the burden
would be offset by savings of £445.7 million in dialysis transportation costs and
patient and carer productivity.

Table 10. Economic impact of combined interventions

Scenario
Direct costs (£) Indirect costs (£) Total costs (£) QALYs ICER (£)
(Year 1-10)
Base case 70,683,534,208 20,334,744,603 91,018,278,811 71,662,137
Combined
71,064,652,248 19,889,062,335 90,953,714,583 71,711,711 7,688
interventions
Difference 381,118,041 (445,682,268) (64,564,228) 49,574
% change 0.5% -2.2% -0.1% 0.1%

81
The QALYs gained from combining the interventions are greater than looking at
each intervention alone (Figure 18). The sum of the QALYs gained from the four
interventions individually (71,711,171) is less than the total effect of combining the
interventions together (71,711,711), a difference of an additional 540 QALYs.

Figure 18. QALYs gained by intervention

Figure 18. QALYs gained by intervention

71,720,000
1,154 540 71,711,711
23,343
71,710,000

71,700,000

71,690,000 20,374

71,680,000

71,670,000 4,164
71,662,137

71,660,000

71,650,000

71,640,000
Base case Intervention 1 Intervention 2 Intervention 3 Intervention 4 Interaction Combined
Factor

82
For the direct costs to the NHS, interventions 1, 2 and 3 are cost generating
(Figure 19). However, intervention 4 is cost-saving at £51.8 million pounds, since
pre-emptive transplants reduce the probability of patients transitioning to
dialysis, which is a more expensive health state. The combination of the four
interventions generates an additional £12.6 million in direct costs to the NHS.

Figure 19. Incremental direct costs by intervention

Figure 19. Incremental direct costs by intervention

Base case

Intervention 1:
Earlier/improved diagnosis
£74,753,141

Intervention 2:
£228,769,763
Improved CKD management

Intervention 3: £116,789,545
Use of SGLT -2 inhibitors

Intervention 4:
Increased rates of (£51,766,866)
transplantation

Interaction factor £12,572,459

Combined £71,064,652,248

83
All of the interventions individually or combined show a cost-effective or cost-saving
ICER (Figure 20).

Figure 20. Summary of ICERs in the unconstrained view

Figure 20. Summary of ICERs in the unconstrained view

40,000

30,000
NICE ICER threshold (20,000-30,000)
20,000

10,000
ICER £

0
Intervention 1 Intervention 2 Intervention 3 Intervention 4 Combined Combined
interventions interventions
-10,000 (unconstrained) (constrained)

-20,000

-30,000
Saves money
-40,000

-50,000

84
Intervention 1: early/improved diagnosis

Based on feedback from stakeholders, earlier and improved diagnosis has been
cited as an important strategy for reducing the economic burden of CKD. Some
forms of screening for CKD have previously been found to be cost-effective, as
early detection can prevent the progression of the disease and the need for more
expensive interventions.137, 138 In addition, interventions such as lifestyle modifications
and medication can reduce the risk of complications associated with CKD, such as
CVD.136 Unlike for other chronic conditions with established screening strategies, there
has been limited consensus by governments and health systems to prioritise early
screenings and interventions for CKD.129 The burden of CKD falls disproportionately
on people with lower socio-economic status as they have a higher prevalence for
CKD, more limited access to treatment and poorer outcomes.129 Prioritising earlier
and improved CKD diagnosis becomes a health equity imperative.

The earlier/improved diagnosis intervention speeds up the transition of patients from

the undiagnosed pathway to the diagnosed pathway (Figure 21). Compared to the
base case, earlier/improved diagnosis led to a reduction in the number of people
who received transplants (33), needed dialysis (389) or had a CVD event (28), and
it avoided 581 deaths by 2033. The modest results were primarily driven by a small
number of people affected by the intervention and relatively short time horizon. As a
result of an earlier diagnosis, more people remained in CKD stages 1-2 (771) and CKD
stages 3-5 (464) by year 10 (Table 11). The primary impact of the intervention led to
approximately 17,000 patients diagnosed earlier, on average per year, compared
to the base case. By 2033, the intervention had an ICER of £17,954, which is below the
NHS threshold for cost-effectiveness.

Figure 21. Intervention

Figure121.
schematic: early/improved
Intervention 1 schematic: diagnosis
Early/improved diagnosis

UK population

Undiagnosed Undiagnosed Undiagnosed Undiagnosed Dialysis Post-transplant

CKD 1 CKD 2 CKD 3 CKD 4 care

1 Mortality

Diagnosed Diagnosed Diagnosed Diagnosed Diagnosed Transplant

CKD 1 CKD 2 CKD 3 CKD 4 CKD 5 (no KRT) (acute event)

Population with CKD – includes both diagnosed and undiagnosed patients

CVD (acute event)

Post-CVD

85
Table 11. Clinical impact of intervention 1

Total
Prevalence (year 10) Incidence (year 10)
(years 1-10)

Scenario CKD 1-2 CKD 3-5 Dialysis Transplant CVD Death

Base case 3,742,425 3,444,060 142,918 11,663 192,970

Intervention 1 3,743,196 3,444,524 142,529 11,630 192,942

Difference 771 464 (389) (33) (28) (676)

% change 0.02% 0.0% -0.3% -0.3% -0.0% -0.01%

The model estimated the implementation of intervention 1 would increase

the burden of CKD by £43.5 million. primarily driven by the cost of additional
testing and general practitioner appointments. Earlier diagnosis was
estimated to save patients and carers approximately £31.3 million. Overall,
4,164 QALYs would be gained over 10 years (Table 12).

Table 12. Economic impact of intervention 1

Scenario
Direct costs (£) Indirect costs (£) Total costs (£) QALYs ICER (£)
(Year 1-10)
Base case 70,683,534,208 20,334,744,603 91,018,278,811 71,662,137

Intervention 1 70,758,287,348 20,303,477,074 91,061,764,422 71,666,302 17,954

Difference 74,753,141 (31,267,529) 43,485,612 4164

% change 0.1% -0.2% 0.05% 0.01%

Screening programmes and better diagnosis technologies may take longer to

generate benefits than the modelled time horizon since patients take time to
progress through the various cost-generating stages of disease progression.
As such, cost-savings for intervention 1 may not be realised until a couple
years after the modelled time horizon. To demonstrate when the intervention
becomes cost-effective and eventually cost-saving, the ICER was forecast using
a logarithmic regression formula. The modelled ICERs showed the intervention
was increasingly cost-effective across the 10-year time horizon (Figure 22).
At year 10, the intervention was below the NICE cost-effectiveness threshold
range of £20,000-£30,000, with an ICER of £17,954. The forecast estimated
the intervention becoming cost-saving in year 13 (ICER of -£3,864).

86
 Figure 22. Projected ICER for intervention 1
Figure 22. Projected ICER for intervention 1

3,000,0000

2,250,000

1,500,000
ICER £

750,000
17,954 1,983 -9,277

‘-0

8,339 -3,864 -14,317

‘(750,000)
0 4 8 12 16
Modelled year
Modelled ICER Predicted ICER

Intervention 2: improved CKD management

Optimal CKD management can reduce the progression of CKD. Controlling

blood pressure (hypertension) through the use of RAS antagonist drugs (e.g.
ACEs or ARBs) has shown benefits in reducing cardiovascular events, CKD
progression and mortality.131 ACEs and ARBs are recommended as a first-line
(standard of care) therapy option for people with CKD who have hypertension,
diabetes or proteinuria (ACR >30 or PCR >50), which equates to approximately
83.3% of the CKD population.23, 24 Discussions with clinical stakeholders and
additional external expert validation have shown that only 53.3% of the eligible
CKD population is receiving the standard care with ACEs or ARBs.24

Implementation of intervention 2 aimed to capture patients with unmanaged

CKD or those who were untreated with standard-of-care treatments. This
was implemented within the model by reducing the transition probabilities
between the health states in the diagnosed pathway to demonstrate a
reduction in CKD progression (Figure 23).

87
Figure 23. InterventionFigure
2 schematic: improved
23. Intervention CKD
2 schematic: management
Better CKD management

UK population

Undiagnosed Undiagnosed Undiagnosed Undiagnosed Dialysis Post-transplant

CKD 1 CKD 2 CKD 3 CKD 4 care

Mortality

Diagnosed Diagnosed Diagnosed Diagnosed Diagnosed Transplant

CKD 1 CKD 2 CKD 3 CKD 4 CKD 5 (no KRT) (acute event)
2
Population with CKD – includes both diagnosed and undiagnosed patients

CVD (acute event)

Post-CVD

Improved CKD management led to more people remaining in CKD stages 3-5
(6,524) compared to the base case, since people progress through the model
slower (Table 13). With slower progression, further downstream effects include
fewer transplants (173) and CVD events (155). Additionally, 2,048 people avoided
dialysis by year 10 and 3,491 avoided death over the 10-year time period.

Table 13. Clinical impact of intervention 2

Total years
Prevalence (year 10) Incidence (year 10)
(1-10)

Scenario CKD 1-2 CKD 3-5 Dialysis Transplant CVD Death

Base case 3,742,425 3,444,060 142,918 11,663 192,970

Intervention 2 3,742,373 3,450,583 140,870 11,490 192,815

Difference - 6524 (2048) (173) (155) (3,491)

% change 0.0% 0.2% -1.4% -1.5% -0.1% -0.05%

The model estimated that implementing intervention 2 would increase the

direct cost to the NHS by £228.8 million at the end of the time horizon (Table 14).
However, costs would be offset by savings due to dialysis transportation and
productivity costs of £188.2 million. Overall, 20,374 QALYs would be gained over 10
years. Having improved CKD management as an intervention is cost-effective,
with an ICER of £11,229.

88
Table 14. Economic impact of intervention 2

Scenario
Direct costs (£) Indirect costs (£) Total costs (£) QALYs ICER (£)
(Year 1-10)
Base case 70,683,534,208 20,334,744,603 91,018,278,811 71,662,137

Intervention 2 70,912,303,970 20,146,524,173 91,058,828,144 71,682,511 11,229

Difference 228,769,763 (188,220,430) 40,549,333 20,374

% change 0.3% -0.9% 0.04% 0.03%

Intervention 3: use of SGLT-2 inhibitors

SGLT-2 inhibitors have demonstrated significant benefits in delaying

progression of kidney disease and reducing cardiovascular events in
people with CKD with or without diabetes. While SGLT-2 inhibitors have
been approved for use in treating type 2 diabetes since 2013, dapagliflozin
was approved in 2022 for use in CKD patients with or without diabetes.24
Dapagliflozin is indicated for CKD stage 3. The benefit of this intervention was
applied in the model by adjusting the transition probabilities to represent a
reduction in the progression to ESKD and cardiovascular events (Figure 24).

Figure 24.Figure 24. Intervention

Intervention 3 schematic:use
3 schematic: Use of
ofSGLT-2i
SGLT-2 to reduce CVD events and progression to ESKD
inhibitors

UK population

Undiagnosed Undiagnosed Undiagnosed Undiagnosed Dialysis Post-transplant

CKD 1 CKD 2 CKD 3 CKD 4 care

Mortality

Diagnosed Diagnosed Diagnosed Diagnosed Diagnosed Transplant

CKD 1 CKD 2 CKD 3 CKD 4 CKD 5 (no KRT) (acute event)
3
Population with CKD – includes both diagnosed and undiagnosed patients

CVD (acute event)

Post-CVD

The model showed that increasing the use of SGLT-2 inhibitors in people with
CKD and slowing the progression of ESKD increased the number of people
remaining in CKD stages 3-5 by year 10 compared to the base case (Table 15).
However, in turn, fewer transplants (164) and CVD events (2,397) occurred
by year 10. Additionally, 1,960 people avoided dialysis at the end of the time
horizon. Increased SGLT-2 inhibitor use also led to 5,611 deaths avoided over
the time horizon.
89
Table 15. Clinical impact of intervention 3

Total
Prevalence (year 10) Incidence (year 10)
(years 1-10)

Scenario CKD 1-2 CKD 3-5 Dialysis Transplant CVD Death

Base case 3,742,425 3,444,060 142,918 11,663 192,970

Intervention 3 3,742,349 3,461,157 140,958 11,500 190,573

Difference - 17,097 (1,960) (164) (2,397) (5611)

% change 0.0% 0.5% -1.4% -1.4% -1.2% -0.07%

Increasing uptake of SGLT-2 inhibitors in people with CKD decreased the overall
cost of CKD by £70.9 million over the next 10 years (Table 16). The increase in
direct costs (£116.8 million) to the NHS was primarily driven by the annual drug
costs of dapagliflozin. However, the added benefit of reducing transplants,
CVD events and the number of patients on dialysis decreased indirect costs
by £187.7 million. Overall, 23,343 QALYs were estimated to be gained over
the 10-year period. Increasing the use of SGLT-2 inhibitors is a cost-effective
intervention with an ICER of £5,003.

Table 16. Economic impact of intervention 3

Scenario
Direct costs (£) Indirect costs (£) Total costs (£) QALYs ICER (£)
(Year 1-10)
Base case 70,683,534,208 20,334,744,603 91,018,278,811 71,662,137

Intervention 3 70,800,323,752 20,147,087,994 90,947,411,746 71,685,480 5,003

Difference 116,789,545 (187,656,609) (70,867,064) 23,343

% change 0.2% -0.9% -0.08% 0.03%

Intervention 4: increased rates of transplantation

For patients with advanced renal disease, transplantation is the best form
of renal replacement therapy as it is associated with lower costs and better
outcomes in the long term. Currently, waiting time for a deceased donor kidney
transplant is 2.5-3 years in the UK. Waiting times for a kidney transplant are
long due to a gap in the supply and demand for kidneys.132 Discussions with
clinical stakeholders have recommended increased rates of transplantation as
a viable intervention to improve clinical outcomes. To demonstrate the benefits
of increasing transplantation rates, one illustrative example identified for the
health economic modelling was pre-emptive transplants.

90
Pre-emptive transplants (before dialysis is initiated) have several benefits, such
as lower risk of rejection of the donor kidney, improved survival rates, improved
quality of life, lower treatment costs and avoidance of dialysis.133 The benefits of
pre-emptive transplants are particularly significant in children and adolescents
with ESKD.133 To model the benefits of pre-emptive transplants, the transition
probabilities were adjusted to illustrate an increased number of transplants per
cycle (Figure 25). Additional fixed costs associated with outreach programmes
within the community were incorporated when calculating the costs.
Figure 25. Intervention 4 schematic: Increased rate of transplantation
Figure 25. Intervention 4 schematic: increased rate of transplantation

UK population

Undiagnosed Undiagnosed Undiagnosed Undiagnosed Dialysis Post-transplant

CKD 1 CKD 2 CKD 3 CKD 4 care

Mortality

Diagnosed Diagnosed Diagnosed Diagnosed Diagnosed Transplant

CKD 1 CKD 2 CKD 3 CKD 4 CKD 5 (no KRT) (acute event)
4
Population with CKD – includes both diagnosed and undiagnosed patients

CVD (acute event)

Post-CVD

In the UK, guidelines recommend all patients with CKD stage 5 be assessed
and placed on the kidney transplant waiting list if determined to be within 6
months of their anticipated dialysis start date.139 Studies have found improved
patient and graft survival in pre-emptive transplants compared to transplants
occurring after dialysis.140 Other benefits include reduced overall cost of care
and improved employment status for the patient.140

91
Pre-emptive transplants increased the total number of transplants across the
time horizon compared to the base case (11,663 vs 12,108, respectively). This
will lead to an 0.8% reduction in dialysis at year 10 and avoid 614 deaths over
10 years (Table 17).

Table 17. Clinical impact of intervention 4

Total
Prevalence (year 10) Incidence (year 10)
(years 1-10)

Scenario CKD 1-2 CKD 3-5 Dialysis Transplant CVD Death

Base case 3,742,425 3,444,060 142,918 11,663 192,970

Intervention 4 3,742,417 3,442,797 141,783 12,108 193,053

Difference - (1,262) (1135) 445 83 (615)

% change 0.0% 0.0% -0.8% -3.8% -0.0% -0.01%

While unit costs do not change by increasing transplants, outreach programmes

to increase awareness of transplants will have a fixed cost applied for each year.
Increasing pre-emptive transplants will save the NHS £51.8 million (Table 18). Indirect
costs will also reduce by £41.6 million. The overall financial burden of CKD will reduce
by £93.4 million to £90.9 billion compared to the base case (£91.0 billion). Overall,
1,154 QALYs will be gained over the 10 years. Implementing the intervention for
increasing pre-emptive transplants is cost-saving, with an ICER of -£44,850.

Table 18. Economic impact of intervention 4

Scenario
Direct costs (£) Indirect costs (£) Total costs (£) QALYs ICER (£)
(Year 1-10)
Base case 70,683,534,208 20,334,744,603 91,018,278,811 71,662,137

Intervention 4 70,631,767,341 20,293,107,052 90,924,874,393 71,663,291 -44,850

Difference (51,766,866) (41,637,551) (93,404,418) 1,154

% change -0.1% -0.2% -0.10% 0.00%

92
Scenario and sensitivity analysis

Models always have uncertainty, and it is important to understand the degree

of uncertainty influenced by the inputs chosen in the model. To quantify the
impact each input has on the results, it is standard to run sensitivity analyses
and scenarios in the model. To test the sensitivity of the inputs within the
model, a scenario analysis and one-way sensitivity analysis was conducted.
The scenario analysis tests the interventions in the constrained view where the
current health system’s ability to provide dialysis and transplants is maximised.
The one-way sensitivity analysis tests the impact that changes within a certain
input will have on output results. The one-way sensitivity analysis adjusts select
parameters by ± 20%. One input is adjusted at a time to determine the degree
to which the overall results change. Results for the scenario analysis and one-
way sensitivity analysis are presented by showing the change in ICER for the
combined basket of interventions and assessing whether the interventions
collectively or individually are still cost-effective.

Scenario – constrained view

Within the constrained view, the transition probabilities in the health economic
(cost-effectiveness) model for dialysis and transplants needed to be adjusted
to illustrate the slower transition to stage 5 of CKD. Using the 10 year estimates
for dialysis and transplantation from the epidemiological model, the goal-
seek function in Excel was used to determine the approximate transition
probabilities. The same inputs used in the unconstrained view to model the
interventions were then applied.

People who remain in CKD stage 5 without moving to KRT due to high waiting
times would continue to get sicker. Currently, the model does not capture the
decline in health and the added costs that people with CKD stage 5 are
experiencing due to the restriction of transitioning to dialysis or transplantation
states. Within the constrained view, the transition probability from ESKD to KRT
is low and the true benefit of diverting patients from the dialysis health state
through the modelled interventions is not experienced.

Figure 26 shows the results of the ICER of the constrained view and the
unconstrained view of the combined basket of interventions. The scenario
analysis confirms that the combined interventions fall within the NICE threshold
of £20,000-£30,000. Additionally, interventions 1-3 in the constrained view are
also cost-effective; however, intervention 4 (increased rate of transplantation)
is not cost-effective. Within the constrained view, the benefits of increasing
transplantation are not realised within the health economic model since there
is a minimal reduction in the number of patients moving to dialysis. Dialysis is
a very costly health state. The number of patients who avoid dialysis through
pre-emptive transplants does not offset the magnitude of patients who remain
in CKD stage 5 or move to dialysis, both of which are health states with high
costs and lower economic benefits (QALYs).

93
People who remain in CKD stage 5 without moving to KRT due to high waiting
times would continue to get sicker. Currently, the model does not capture
the decline in health and the added costs that people with CKD stage 5 are
experiencing due to the restriction of transitioning to dialysis or transplantation
states. Within the constrained view, the transition probability from ESKD to KRT
is low and the true benefit of diverting patients from the dialysis health state
through the modelled interventions is not experienced.
Figure 26. Comparison of ICERs for the combined interventions,
Figure 26. Comparison of ICERs for the combined interventions, constrained vs unconstrained view
constrained vs unconstrained view

35,000

30,000

NICE ICER threshold (£20,000-£30,000)

25,000

20,000

15,000

10,000

5,000

0
Unconstrained Constrained

94
One-way sensitivity analysis
The sensitivity analysis was conducted on select input parameters:
• Dialysis transition probability
• Transplant transition probability
• Incidence
• Assumption of the undiagnosed population in intervention 1 who get diagnosed
• Effectiveness of intervention 2 from diagnosed CKD stage 2 to CKD stage 3
• Quarterly cost of SGLT-2 inhibitors in intervention 3
• Assumption of the proposed state of increasing transplants in intervention 4

Figure 27 shows the results of the one-way sensitivity analysis on the ICER for the
combined set of interventions. Effectiveness of intervention 2 from diagnosed
CKD 2 to CKD stage 3 had the largest impact on the combined ICER, followed by
the quarterly cost of SGLT-2 inhibitors in intervention 3, and the dialysis transition
probability. Adjusting the assumption of the undiagnosed population in
intervention 1 who get diagnosed by ± 20% had the lowest impact on the combined
ICER. Overall, the analysis shows that the ICER for the combined interventions
remains cost-effective when changing the inputs. The changes are marginal.

Figure 27. One-way sensitivity analysis

Figure 27. One-way sensitivity analysis

Effectiveness of ACE/ARBs from

diagnosed stage 2 to 3
Quarterly cost of SGLT-2
inhibitor intervention
Dialysis transition probability

Proposed state of
increasing transplants

Incidence

Transplant transition probability

Assumption of proportion Upper

undiagnosed who get diagnosed Lower

- 2,000 4,000 6,000 8,000 10,000 12,000 14,000

ICER £

95
Conclusions and
recommendations
Conclusions

The evidence presented in this report suggests that kidney disease leads
to thousands of premature deaths each year, reduces quality of life and
places a significant economic burden on the NHS, patients with kidney
disease, the people who support them and the wider economy:

1. Chronic kidney disease affects 13% of the global population and is

predicted to be the fifth leading cause of premature death* by 2040.
2. In the UK, approximately 3.25 million adults are living with chronic kidney
disease stages 3-5, and a total of 7.2 million adults have chronic kidney
disease (all stages), more than 10% of the entire population.
3. By 2033, the number of people living with all-stage chronic kidney
disease is projected to reach 7.6 million. This is mainly driven by an ageing
population as well as risk factors such as diabetes, hypertension and
cardiovascular disease, as well as other important factors such as health
and economic inequalities.
4. Amongst those with chronic kidney disease, the proportion with later-stage
chronic kidney disease (3-5) is expected to increase from 45% (3.25 million)
to 51% (3.9 million).
5. Around 615,000 episodes of acute kidney injury occur each year, mainly
among those who are already unwell or hospitalised for another reason.
By 2033, the number of acute kidney injury episodes is projected to rise by
4% to 637,000.
6. The total economic burden of kidney disease in the UK is £7.0 billion, with
£6.4 billion attributable to direct costs to the NHS – about 3.2% of NHS
budgets across the four nations. The total burden of kidney disease could
rise to £13.9 billion by 2033.
7. There is a further estimated £372 million in productivity loss to the UK
economy from from missed work due to dialysis alone. Productivity loss
in the UK could reach up to £2.0 billion by 2033, as a higher proportion of
patients continue living with end-stage kidney disease.
8. In 2023, the cost of dialysis for people with end-stage kidney disease
is £1.05 billion annually, or 0.53% of the NHS budget. In addition to the
direct cost of dialysis, transport for patients on in-centre dialysis costs
approximately £225 million per year. The cost to the NHS of dialysis to
manage kidney disease (per person) is £34,000 per year – more than
three times the annual value of a state pension.

* Premature death can be measured by life years lost, which takes into account frequency of death and age at
which it occurs. It is calculated by multiplying the number of deaths by a global standard life expectancy at
which death occurs.
96
9. Despite its substantial and increasing cost to the NHS, and the urgent need
for new and better treatments driven by research, kidney disease received
only 1.4% of relevant public healthcare research funding – just £17.7 million
in financial year 2021/2022.
10. Economic modelling suggests that improved implementation of four
illustrative healthcare interventions could save more than 10,000 lives by
2033. These interventions individually and collectively are shown to be
cost-effective or cost-saving, where costs to the NHS are offset by quality-
adjusted life years gained.

Recommendations

Strategic
Modelling indicates that significant, cost-effective patient benefits can
be achieved through better implementation of existing technologies and
guidelines for the prevention, management and treatment of kidney disease.
Across the health and care system, a national effort should be made to
improve uptake of these interventions.

Paediatric kidney disease is relatively rare and historically has not received the
attention it deserves. Establishing some oversight of paediatric kidney care from
kidney policymakers, in particular to establish better transition management for
young adults, has been highlighted by stakeholders as important.

The population with chronic kidney disease and end-stage kidney disease is
varied in terms of age, gender, ethnicity and the root causes of illness, and
therefore the same diagnostic techniques, management strategies and
treatments are not effective for all groups. For example, eGFR tests have
been shown to be less sensitive at predicting outcomes in people who are of
South Asian descent. There should be efforts made to personalise the care of
patients with, or at risk of, kidney disease across the disease pathway. These
should include:
• Use of the best possible diagnostic tests based on proven effectiveness
for the demographics of the specific patient
• Genetic testing followed by appropriate management for those at risk of
inherited kidney disease
• Patient choice in treatment, e.g. support with home dialysis for patients
who feel this would better enable them to continue working and
undertaking their usual activities
• Access to new and proven therapies to manage and slow disease
progression in a timely manner
• Creating an environment fostering innovation and its implementation in
real-world settings

Kidney disease is complex and is intertwined with other chronic/serious health

conditions. The NHS and voluntary sector organisations should seek to break
down silos between organisations and teams working on kidney disease and
related conditions such as diabetes, hypertension, cardiovascular disease and
inherited genetic conditions.

97
Modelling suggests that more proactive engagement with people who are at risk
or have kidney disease would be clinically and cost effective, e.g.:
• Peer engagement to improve adherence to disease management strategies
• Engaging in proactive discussions around living donor transplants
• Community outreach to engage underserved groups
However, given the frequent multi-morbidity of people with kidney disease, this
engagement could be even more cost effective if it addressed multiple health
conditions relevant to these populations at the same time. The NHS and voluntary
sector should consider how to pool resources and efforts to collaborate across
multiple programmes of engagement.

Current research funding for kidney disease is just 1.4% of relevant healthcare
budgets, while kidney disease represents 3.2% of NHS budgets, with a risk of
significant growth in this burden. Kidney disease research funding should be
increased in line with the clinical and financial burden of disease.

Clinical
In this report, kidney disease has been referred to as a silent killer, because many
patients are undiagnosed or asymptomatic until they reach a later stage of
disease. Stakeholder interviews have revealed opportunities to improve adherence
to best practice guidelines by making them simpler and more accessible, especially
for primary care, where the huge breadth of conditions general practitioners treat
is a challenge. In addition, measures should be taken to monitor local adherence to
guidelines and intervene where necessary.

To address barriers to implementation, focus is required on how best to provide

knowledge transfer and pathway/process development. This could include closer
collaboration between secondary and primary care, e.g. with regular virtual
consultations between general practitioners and kidney specialists.

A broader transformation of renal services is needed to improve care through

standardisation and knowledge sharing. At the time of writing, in England the
Renal Services Transformation Programme (RSTP) was reviewing adult renal
services and recommending areas where improvements should be made.
The recommendations for service improvement in the areas of early detection,
dialysis and transplantation are in alignment with the findings of this report,
which also addresses the scale of the challenge across the whole of the UK and
the requirements of paediatric services to meet future needs.

Severe kidney disease in children can have a similar impact in terms of mortality
and lifelong disease to cancer. Because chronic kidney disease is a lifelong,
gradually deteriorating condition, children with mild chronic kidney disease are
likely to develop severe chronic kidney disease later in life, and therefore early
intervention and ongoing management is important. At the time of writing,
however, poor infrastructure exists for children with kidney disease transitioning to
adult services. Until recently, services were overseen nationally by a clinical reference
group that included several other paediatric sub-specialties, which may be a cause
for this disconnect. There is now a separate clinical reference group in place for
paediatric renal services, and one of the focus areas should be establishing a more
effective transition to adult services.
98
Research
In the development of this report, several evidence gaps were identified, and
further research should be considered to address them:
• Understanding the rate at which patients progress through the stages
of chronic kidney disease is essential to predicting future demand for
services. However, much of the data currently in the public domain
is out of date, and up-to-date transition probabilities/relative risks of
progression of chronic kidney disease for the whole population and
subgroups are needed.
• Understanding the relative risk/rate of progression for undiagnosed
populations is essential for assessing the cost effectiveness of early
diagnosis and treatment interventions, but there is very little published
literature relevant to the UK. Studies, potentially using real-world
data, comparing the relative rates of progression in diagnosed vs
undiagnosed populations are required.
• Sources such as the renal registries provide data on the numbers of
patients receiving dialysis. However, there is limited data on unmet need
or delays in meeting need, and as more patients progress to later-stage
kidney disease, having real-time data which allows monitoring of any
potential capacity pressures will become increasingly important.
• This report utilises evidence from other European countries to estimate
the economic burden of kidney disease for the UK. UK-specific studies on
the impact of kidney disease on economic productivity are necessary.
• There is evidence of a strong and complex relationship between kidney
disease and mental health. UK-specific studies on this relationship, including
the impact of poor mental health on adherence to treatment, are needed.
• The evidence base relating to rare forms of kidney disease is scarce.
Further research in this area is required to understand the natural history,
determinants (including genetic), treatment effectiveness and burden of
rare forms of kidney disease.
• Paediatric kidney disease is relatively rare and often complex. Better
data and evidence are required to understand the needs of these
patients, e.g. studies characterising their epidemiology, demographics
and broader health needs.
• This report has highlighted the multitude of risk factors for kidney disease,
but evidence on the causal link between diabetes, hypertension, chronic
kidney disease and other risk factors at a population level is scarce. Studies
investigating the relationships between these conditions in a predictive
manner would provide a powerful tool for population health planning.
• There are still large evidence gaps on how Covid-19 has affected and
will continue to affect people with or at risk of kidney disease. At the time
of writing this report, work in this area is ongoing using the OpenSAFELY
platform, and it is important that it continues to be supported.
• There is an opportunity for the four nations of the UK to learn from each
other on the management of kidney disease, but inconsistent data
is a barrier to this. Introducing more consistent data, e.g. extending
the Healthcare England Survey methodology to Scotland, Wales and
Northern Ireland, could be an important enabler for driving better health
outcomes for the entire UK population.

99
Acronyms
ACE, angiotensin-converting enzyme

ACR, albumin-to-creatinine ratio

ADPKD, autosomal dominant polycystic kidney disease

aHUS, atypical haemolytic uraemic syndrome

AKI, acute kidney injury

ARB, angiotensin receptor blocker

ARPKD, autosomal recessive polycystic kidney disease

BAPN, british association for paediatric nephrology

C3G, C3 glomerulopathy

CAGR, compound annual growth rate

CKD, chronic kidney disease

Covid-19, coronavirus disease-19

CRG, clinical reference group

CVD, cardiovascular disease

DDD, dense deposit disease

eGFR, estimated glomerular filtration rate

ESKD, end-stage kidney disease

GFR, glomerular filtration rate

HSE, Health Survey for England

ICER, incremental cost-effectiveness ratio

ICU, intensive care unit

IgAN, IgA neuropathy

KD, kidney disease

KRT, kidney replacement therapy

100
LYL, life years lost

MN, membranous nephropathy

MPGN, membranoproliferative glomerulonephritis

MRC, Medical Research Council

NHS, National Health Service

NICE, National Institute for Health and Care Excellence

NIHR, National Institute for Health and Care Research

NPHP, nephronophthisis

ONS, Office for National Statistics

PCR, protein-to-creatinine ratio

PH, primary hyperoxaluria

PICOTS, population, interventions, comparators, outcomes, timeframe, and study design

PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PSSRU, personal social services research unit

QALY, quality-adjusted life year

RAS, renin-angiotensin system

RSTP, renal service transformation programme

SGLT-2, sodium-glucose transport protein 2

SLR, systematic literature review

SRNS, steroid-resistant nephrotic syndrome

SSNS, steroid-sensitive nephrotic syndrome

TLR, targeted literature review

TSC, tuberous sclerosis

UK, United Kingdom

UKKA, UK Kidney Association

UKRI, United Kingdom Research and Innovation

UTI, urinary tract infection

101
Definitions
1. Constrained view: Scenario of modelling where growth for dialysis and
transplantation is estimated based on NHS historical rates.
2. Co-morbidity: The simultaneous presence of two or more diseases or
medical conditions in a patient.
3. Dialysis: A type of kidney replacement therapy that replaces the blood-
filtering function of the kidneys.
4. Dyslipidaemia: Abnormally elevated cholesterol or fats (lipids) in the blood.
5. Endothelial dysfunction: A type of non-obstructive coronary artery disease
in which there are no heart artery blockages.
6. Epidemiology: The method used to find the causes of health outcomes
and diseases in populations. In epidemiology, the patient is the community
and individuals are viewed collectively.
7. Evidence synthesis: The process of bringing together information from
a range of sources and disciplines to inform debates and decisions on
specific issues.
8. Grey literature: Materials and research produced by organisations outside of
the traditional commercial or academic publishing and distribution channels.
9. Hazard ratio: A measure of how often a particular event happens in one
group compared to how often it happens in another group, over time.
10. Health state: A clinical event/stage used in models. All events in a disease
pathway are represented as transitions from one state to another.
11. Hyperlipidaemia: Abnormally elevated levels of any or all lipid in the blood.
12. Kidney replacement therapy: A term used to encompass treatments used
for renal failure. These treatments include dialysis and transplantation.
13. Nephrotoxic agents: All drugs with the potential to generate kidney
damage and to reduce renal function.
14. Oxalate: Another term for salt.
15. Oxidative stress: Oxidative stress reflects an imbalance between the
systemic manifestation of reactive oxygen species and a biological
system’s ability to readily detoxify the reactive intermediates or to repair the
resulting damage.
16. Schematic: Representation of a drawing or diagram.
17. Search string: A combination of keywords, truncation symbols and Boolean
operators you enter into the search box of a library database or search engine.
18. Tunnel state: All patients transition out of the health state at the next cycle.
19. Unconstrained view: Scenario of modelling where growth for dialysis and
transplantation is estimated based on transition probabilities for disease
progression. This represents future potential unmet need.
20.Underserved: This may include people from ethnic minority and deprived
communities, those with severe mental health conditions and those with
low levels of health literacy.

102
References
1. Centers for Disease Control and Prevention (CDC). What You Should Know
About Chronic Kidney Disease. https://www.cdc.gov/kidneydisease/
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Appendices
Appendix A - TLR protocol summary
Topic Inclusion Critera
Patients with:
• Acute kidney disease
• Chronic kidney disease
Study population (P) • End-stage kidney disease
• Other kidney diseases such as rare and inherited kidney disease
(e.g. as Fabry disease, cystinosis, and polycystic kidney disease)
Age, race, and gender: No restriction
Intervention (I) No restriction on intervention
Comparator (C) No restriction on comparator
Epidemiology evidence
• Incidence and incidence rates of kidney disease and comorbidities
• Prevalence and prevalence rates of kidney disease and comorbidities
• Incidence/prevalence over time
• Mortality
• The evidence will be categorized and detailed by country and
Integrated Care System/health system geographies
• Impact of Covid-19 infection/long Covid-19 on symptoms,
complications (arterial and thromboembolic)
• Impact of Covid-19 on the incidence, prevalence, mortality among
patients with kidney disease/CKD/ ESKD/kidney transplant
recipients/on haemodialysis
Economic evidence
• Direct costs of kidney disease, including direct medical pharmacy
healthcare costs for complications and comorbidities (such as for
cardiovascular disease and dyslipidaemia, anaemia, malnutrition,
mineral and bone disorders, pruritus, decreased functional status,
Outcome (O) etc.), cost of dialysis (home based, in centre), transplantation, end-
of-life care for kidney disease, admission/hospitalisation costs
• Resource use: Hospitalisation, length of ICU stays, intervention
usage, increased admission rate, home care
• Indirect costs: Disease-related production losses due to patient
and caregiver absenteeism/presenteeism from work, loss of
employment, productivity, out-of-pocket costs to attend hospital
clinics, insurance premiums
• Patients and family/caregiver costs: Travel, annual loss of income,
formal and informal care, loss of disposable income
• Evaluation details (perspective, time horizon, source of cost,
resource use data, cost effectiveness, cost year, model, model
description and justification)
• Cost analysis: Assumptions, hypothesis, type of cost, year of cost,
budget impact details, resource use)
• CEA: Cost effectiveness or cost utility, ICER, QALY
• Impact of Covid-19 infection/long Covid-19 on the economic and
resource use burden of patients and their caregivers
113
 Topic Inclusion Critera
Epidemiology evidence
Any study reporting epidemiology data, including cohort studies,
cross-sectional, registry studies
Study design (S)
Economic evidence
Any studies reporting original cost and/or resource use data
Economic evaluations for cost/resource use input data

Language of full text English-language publications and English-language abstracts of

article (L) foreign language

Databases
Year of publication • Epidemiological review: 2017-2022
(Y) • Economic review: 2017 -2022
• Conferences: 2019-2022

Country of study UK

114
ZS is a management consulting and technology firm focused on transforming
global healthcare by driving toward a connected ecosystem. For more
information, please visit our website: https://www.zs.com/.

Authors: Barry Farrimond, George Agathangelou, Larisa Gofman, Rucha Kulkarni

and Jacob Jaffe.
115
 This report has been co-funded by Kidney Research UK and the following
industry supporters: AstraZeneca, CSL Vifor, GSK, Hansa Biopharma
and Proteomics International Laboratories.

These companies had no control or editorial input to the contents of this report.