NEPHROLOGY 2009; 14, 367373

nep_1113

doi:10.1111/j.1440-1797.2009.01113.x

367..373

Review Article

Review article: Early detection of chronic kidney disease in

Australia: Which way to go?
TIMOTHY MATHEW1 and OLIVIA CORSO2
1

Kidney Health Australia, Medical Section, Kent Town, and 2Kidney Health Australia, Health Services,
Adelaide, South Australia, Australia

SUMMARY: Early detection of chronic kidney disease (CKD) followed by appropriate clinical management
appears the only means by which the increasing burden on the health-care system and affected individuals will
be reduced. The asymptomatic nature of CKD means that early detection can only occur through testing of
individuals. The World Health Organization principles of screening for chronic disease can now be largely fulfilled
for CKD. The risk groups to be targeted, the expected yield and the tests to be performed are reviewed. For a
screening programme to be sustainable it must carry a greater benefit than risk of harm for the participant and
be shown to be cost-effective from the community point of view. Whole population screening for CKD is
impractical and is not cost-effective. Screening of those at increased risk of CKD could occur either through
special events run in the community, workplace or in selected locations such as pharmacies or through
opportunistic screening of high-risk people in general practice. Community screening programmes targeted at
known diabetics, hypertensives and those over 55 years have been described to detect 93% of all CKD in the
community. The yield of CKD stages 35 from community screening has been found to vary from 10% to 20%.
The limitations of screening programmes including the cost and recruitment bias are discussed. The most
sustainable and likely the most cost-efficient model appears to be opportunistic general practice screening. The
changing structure of general practice in Australia lends itself well to the requirements for early detection of CKD.
KEY WORDS:

albuminuria, chronic kidney disease (CKD), glomerular filtration rate (GFR), proteinuria.

The burden of chronic disease attributable to kidney disease

in Australia is increasing. This is best-documented in those
with kidney failure accepted on to Australian dialysis and
transplant treatment programmes where the prevalence of
patients on dialysis has more than doubled in the last
12 years.1 The prevalence of earlier stages of chronic kidney
disease (CKD) in Australia is not well-documented over
time and is confounded by changes in the measurement and
reporting of serum creatinine concentrations and the relatively recent definition of stages of CKD. There seems little
doubt however that the Australian prevalence of early CKD
has risen in recent years driven by the increased numbers of
people with diabetes and the increasing age of the population. The situation is likely similar to the USA where the
prevalence of stages 14 CKD was shown to increase from
10% in 19881994 to 13.1% in 19992004.2

Correspondence: Professor Timothy Mathew, Kidney Health

Australia, Medical Section, 45 Wakefield Street, Kent Town, SA 5067,
Australia. Email: tmathew@bigpond.net.au
Accepted for publication 17 February 2009.
2009 The Authors
Journal compilation 2009 Asian Pacific Society of Nephrology

The early recognition of CKD is made difficult by its

largely asymptomatic nature. One consequence of this is
that about a quarter of all patients in Australia present to
their nephrologist in kidney failure less than 90 days before
starting dialysis and this number is showing no sign of
improving with time.3 An early diagnosis of CKD allows
preventive measures to be put in place that may favourably
affect clinical outcomes and in those with progressive
kidney failure facilitate a smooth, orderly and less morbid
transition on to dialysis and transplant programmes.
The detection of CKD early in its course relies on the
performance of tests on urine (albumin or protein) and
blood (serum creatinine), and these together with a blood
pressure measurement have been popularly called a kidney
health check. There is no other simple clinical means to
establish the presence of kidney damage and to classify it
into stages by severity.4
It is important to recognize at the outset that screening
can occur in two ways population-based screening where a
test is offered to all individuals in a targeted group and
opportunistic screening when a test is offered to an individual without symptoms of the disease when they present
to the health-care system for other reasons. Screening for

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T Mathew and O Corso

CKD is not currently practiced in Australia. This article

reviews the principles underlying and justifying the establishment of a screening programme for CKD. The following
questions will be addressed:
1 The principles of screening for chronic disease
applied to CKD.
2 Who should be screened and what is the likely yield
from screening programmes?
3 How should CKD be screened?
4 Is there advantage for the participant in the screening
programme?
5 Are CKD screening programmes cost-effective?
6 Where to for Australia with CKD screening?

wealth Government, the current and growing spend on

renal replacement and the contribution of CKD to premature cardiovascular morbidity and mortality have been cost
in the UK at 2% of the National Health Service budget.9

1 PRINCIPLES OF SCREENING AS APPLIED TO

CKD EARLY DETECTION

The natural history of the condition, including

development from latent to declared disease should be
adequately understood

The World Health Organization (WHO) principles of

screening for disease were published 40 years ago (Table 1)5
and continue to underpin current screening recommendations in Australia.6 It is instructive to consider the situation
with CKD screening against these criteria.
The condition (CKD)
The condition should be an important health problem
The scope of the health problem in Australia posed by CKD
has recently been reviewed by the Australian Institute of
Health and Welfare7 and on a global level.8 Although not
recognized as a health priority in Australia by the CommonTable 1 World Health Organization principles of early disease
detection5
Condition
The condition should be an important health problem.
There should be a recognizable latent or early symptomatic
stage.
The natural history of the condition, including
development from latent to declared disease should be
adequately understood.
Test
There should be a suitable test or examination.
The test should be acceptable to the population.
Treatment
There should be an accepted treatment for patients with
recognized disease.
Screening programme
There should be an agreed policy on whom to treat as
patients.
Facilities for diagnosis and treatment should be available.
The cost of case findings (including diagnosis and
treatment of patients diagnosed) should be economically
balanced in relation to possible expenditure on medical
care as a whole.
Case findings should be a continuing process and not a
once and for all project.

There should be a recognizable latent or early

symptomatic stage
Chronic kidney disease characteristically is a silent condition yet kidney damage can be readily demonstrated by
simple tests (see following)

The natural history of CKD has been intensively studied

over the last 50 years and although complex, risk factors for
progression based on clinical tests have been established.
The incidence, prevalence and trends of progressive decline
in kidney function, the association with increased morbidity
and mortality and the burden of disease by age and sex are
known.7 The importance of proteinuria as a risk marker
for progressive decline in kidney function has been
emphasized.10

Tests for CKD

There should be a suitable test or examination
The tests for establishing the presence of CKD are simple,
cheap and widely available. The sensitivity and specificity of
tests used for detection of CKD has been reviewed by Jaar
et al.11 Urine testing for albumin demonstrates acceptable
sensitivity and high specificity. The use of serum creatinine
concentration and estimated glomerular filtration rate
(GFR) has limitations, and efforts are underway to improve
the performance of these measures. It should be stressed that
the definition of CKD calls for the abnormalities to persist
for more than 3 months a severe restriction on screening
for CKD as a one-off test. Any screening results can only be
regarded as suggestive, and confirmation of any abnormalities requires serial tests over time.7 The advantages in
targeting CKD testing to high-risk groups have been
demonstrated.12

The test should be acceptable to the population

The simple tests for CKD should prove readily acceptable to
the target population including Aboriginal and Torres Strait
Islander people who have a high prevalence of CKD. A
finger prick-based serum creatinine test is currently under
development and is being validated and standardized. Its
availability for use in the field will assist in the acceptability
of CKD testing.
2009 The Authors
Journal compilation 2009 Asian Pacific Society of Nephrology

369

Early detection of chronic kidney disease

Table 2 eGFR clinical action plan15

eGFR (mL/min
per 1.73 m2)
390
6089

Description
Stage 1 CKD kidney
damage with normal
kidney function
Stage 2 CKD kidney
damage with mild
kidney function

3059

Stage 3 CKD moderate

kidney function

1529

Stage 4 CKD severe

kidney function

<15

Stage 5 CKD end-stage

kidney disease

Clinical action plan

Further investigation for CKD may be indicated in those at
increased risk:
blood pressure
assessment of proteinuria
urinalysis
Cardiovascular risk reduction:
blood pressure
lipids
blood glucose
lifestyle modification (smoking, weight, physical activity, nutrition
and alcohol)
As above, plus:
monitor eGFR 3 monthly
avoid nephrotoxic drugs
prescribe anti-proteinuric drugs (ACE inhibitors and/or ARB) if
appropriate
address common complications
ensure drug dosages appropriate for level of kidney function
Consider indications for referral to a nephrologist
As above, plus, referral to nephrologist is usually indicated for physical
and psychosocial preparation for renal replacement therapy (dialysis,
pre-emptive transplantation and transplantation) or conservative
medical management
As above, plus referral to a nephrologist

Imaging or biopsy abnormalities, or proteinuria/haematuria. Hypertension, diabetes, smoker, age > 50 years, obesity, family history of kidney
disease, Aboriginal and Torres Strait Islander people. CKD, chronic kidney disease; GFR, glomerular filtration rate; ACE, angiotensin converting
enzyme; ARB, angiotensin receptor blocker.

Systems should be in place for evidence-based follow up

of all people with a positive screening test
The management of screen-detected cases of CKD would
essentially be in the primary health-care system. This is
widely available to all Australians irrespective of location or
socioeconomic status.
Treatment of CKD
There should be an accepted treatment for patients with
recognized disease
The evidence-based clinical action pathways for CKD in its
various stages have been determined13,14 and published in
Australia (see Table 2).15
Screening programme for CKD
There should be an agreed policy on whom to treat
as patients
While there is consensus in some areas of CKD management
(e.g. proteinuria >1 g/day in a young person) there remains
uncertainty about how to approach a 75-year-old with a mild
2009 The Authors
Journal compilation 2009 Asian Pacific Society of Nephrology

reduction in eGFR (e.g. 55 mL/min per 1.73 m2) and no

other abnormalities. Further studies are needed to establish
the best care pathway in the elderly with mild CKD.
Facilities for diagnosis and treatment
should be available
The management of CKD in its early phases requires no
expensive diagnostic tests or treatment. The essential care is
consistent with cardiovascular risk reduction at the primary
care level.
The cost of case findings (including diagnosis and
treatment of patients diagnosed) should be economically
balanced in relation to possible expenditure on medical
care as a whole
The cost-effectiveness of early detection (opportunistic
screening of 5069-year-olds in general practice) and intervention to prevent progression of CKD in Australia has
been established.16 Savings incurred through reduction in
the numbers progressing with CKD into the high-cost end
of treating end-stage kidney failure provides a balance to
the costs of screening and may potentially represent a
genuine saving. Further studies are needed to assess the

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cost-effectiveness of community- or work-based screening

programmes. There is a paucity of information on clinical
outcomes recorded in screen-detected cases although there
seems little reason to doubt that the benefit of treatment
would be similar to that demonstrated in cases found
through conventional channels.
Case findings should be a continuing process and not a
once and for all project
This recommendation would well apply to CKD where
there is a continuing risk of acquiring the condition with
increasing age and the development of diabetes, hypertension and obesity.
Jaar et al. have recently published the Principles of
Screening for Kidney Disease and concluded that the
majority of the Wilson and Junger (WHO) criteria could be
satisfied for CKD screening and evidence is mounting that a
population based screening programme should be implemented in certain high risk groups. They further conclude
that further studies of the benefits, risks and costs of screening for CKD including randomized controlled trials are
still needed.11
Jaar et al. identified the lack of published randomized
trials of clinical outcomes in screen-detected cases of CKD
and acknowledged concerns about the validity of and bias
in screening methods, and the need for further costeffectiveness studies based on hard clinical outcomes.
2 WHO SHOULD BE SCREENED FOR CKD AND
WHAT IS THE LIKELY YIELD OF MODERATE TO
SEVERE CKD?
The prevalence of CKD in Australian adults is about 16%
with 2.4% having proteinuria and 7.8% CKD stages 35
(from AusDiab relying on a one-off testing of the sampled
population).7 There is agreement that population-wide
screening for CKD by early detection of urine protein is not
cost-effective17 or is at best a promising primary prevention
strategy.18
The case for testing individuals at high risk for CKD has
been made in position statements published by the National
Kidney Foundation of USA19 and a position statement published from the not-for-profit organization KDIGO (Kidney
Disease Improving Global Outcomes) recommending All
countries should have a targeted screening programme for
CKD focusing on those people known to have diabetes,
hypertension and cardiovascular disease.20
A large-scale general health survey from Norway in
65 000 people from a single community (with a 71%
response rate) begun in 1995 throws considerable light on
who to screen. The study concluded that screening people
with hypertension, diabetes or age > 55 years was the most
effective strategy to detect people with CKD. This approach
to targeting would have screened 37% of the population,
detected 93% of all CKD present in the community and
required 8.7 people to be screened per detected case of CKD
stages 35. Other strategies of targeting detected a lower

T Mathew and O Corso

percentage of CKD and were considered less effective.12

Given the high prevalence of CKD in some indigenous
communities it would seem appropriate in Australia to add
Aboriginal and Torres Strait Islander people to the targeted
cohort.
The US KEEP (Kidney Early Evaluation Program)
targets people with self-reported diabetes or hypertension or
those with a first-order relative with hypertension, diabetes
or kidney disease and found 19% of participants to have
CKD stages 35. The KEEP participants are characterized
by overrepresentation of Afro-Americans and women that
might explain the high yield.21 The Australian KEY (Kidney
Evaluation for You) pilot programme chose to target those
with known diabetes, hypertension and those over 50 years
and yielded 9.7% of participants to have CKD stages 35
(Mathew T, Corso O, 2009). The KDIGO recommends
targeting patients with hypertension, diabetes and cardiovascular disease.4 Clearly the higher the number of risk
groups included in the target cohort the higher the yield of
CKD but the less efficient the programme because of the
greater numbers screened. A reasonable conclusion might
be to follow the Norwegian experience of targeting people
with diabetes and hypertension and to arguably elevate the
age cut point to >60 years this would likely further
improve the efficiency with little loss in the number of cases
of serious kidney disease cases detected.

3 HOW SHOULD CKD BE SCREENED?

The progressive reduction of GFR in those people who are
destined to progress into kidney failure is the hallmark
of progressive kidney damage. The improved recognition of
early reduction in GFR through the automatic reporting of
eGFR (based on serum creatinine measurement) has considerably advanced our ability to find early cases of people at
special risk of developing kidney failure. The estimation of
GFR from a creatinine-based measurement will always have
its limitations, but improvement in the standardization of
measurement of creatinine has already occurred and a new
formula for estimating GFR has been developed that is more
accurate especially at a higher eGFR and is likely to replace
the current MDRD eGFR formula.22
However the risk of progression to kidney failure even in
those with a moderate reduction of GFR (stage 3) has been
shown to be small. The Norwegian study tracked 2389
people with an eGFR of 4559 mL/min per 1.73 m2 for
8 years and showed only 0.4% progressed to end-stage renal
failure. Of those with an eGFR of 3045 mL/min per
1.73 m2 only 1.3% progressed to end-stage renal failure.12
Thus although measurement of GFR is integral to any CKD
screening programme additional tests to separate those at
special risk of progression are needed.
Proteinuria has emerged as the most important determinant of likely progression to kidney failure10,23 and has been
shown to be a strong independent predictor of kidney
failure in a mass screening setting.24 The combination of
GFR reduction and proteinuria or albuminuria is especially
important as a risk factor for end-stage renal failure as shown
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371

Early detection of chronic kidney disease

in the MRFIT study where a GFR < 60 mL/min together

with proteinuria dipstick 2+ or more had a relative risk of 33
for progression to end-stage renal failure compared with
those with a normal GFR and no proteinuria.25 Albumin/
creatinine ratio has also been reported as being associated
with a higher rate of GFR decline in men,26 and given the
high number of people with diabetes targeted in CKD
screening albuminuria assessment appears essential.
Other biomarkers for the presence of CKD that are able
to improve on the accuracy of present tests in indicating an
increased propensity for progression are being sought. Cystatin C is being assessed as an alternative to creatinine for
GFR estimation but appears to offer no advantage when the
GFR is <60 mL/min. Urine biomarkers such as KIM-1 and
NAG are promising for early diagnosis of acute kidney
injury, but little help is on the horizon for CKD.27
Thus for the immediate future serum creatinine measurement, urine dipstick for protein and urine albumin/
creatinine ratio (along with blood pressure measurement)
are the mainstay of any CKD screening programme. The
measurement at point of care of urine albumin and
creatinine is well-established, and recent advances have
occurred in the technical aspects of measuring serum creatinine at the point of care. We have recently validated
venous sampling of blood for an IDMS-aligned serum creatinine measurement and are in the process of validating
finger prick sampling (Shephard M, Corso O, 2009). Point
of care assessment of these tests allows the feedback of
results to participants within minutes of sampling and
enhances the efficiency of communication within the
screening process.

4 IS THERE ADVANTAGE FOR THE

PARTICIPANT IN CKD SCREENING?
The early detection of CKD allows preventive measures to
be put in place that may favourably affect clinical outcomes
and facilitates a smooth and orderly transition on to dialysis
and transplant programmes in those who progress under
continuing care. The fact, as described above, that the risk
of progressing to kidney failure is small needs to be modified
by the increasingly appreciated reality that one reason for
this is the competing risk of death from cardiovascular
disease. For those with CKD stage 3 and followed for 5 years
this risk of cardiovascular mortality exceeds the risk of endstage renal failure by a factor of almost 20 times.28 Thus any
preventive measure that follows the screen-detected diagnosis of CKD must include cardiovascular risk reduction.
While controlled trials have shown significant advantage to
participants through reduction in the number progressing to
kidney failure with the use of angiotensin-active agents,
little attention has been paid to improved cardiovascular
outcomes in those with CKD.
A positive result obtained at a screening programme can
create harm through anxiety in the participant, and this is
particularly so when there is an incidence of false positives.
Mis-categorization of a significant number of people to CKD
stage 3 may occur given the precise cut point of GFR at
2009 The Authors
Journal compilation 2009 Asian Pacific Society of Nephrology

60 mL/min and the lack of precision of the creatinine measurement. Improvement in creatinine standardization, the
new eGFR formula and the possible introduction of agebased reference intervals will help reduce the frequency of
mis-categorization. The diagnosis of CKD requires establishing the persistence of the abnormalities over a 3 month
period. Any screening programme thus relies on anyone
with an abnormality detected suggestive of CKD being
referred to their general practitioner for further tests, advice
and follow up.
The answer to the question Is there advantage to the
participant in CKD screening? awaits careful assessment
in randomized trials of cardiovascular risk reduction and
long-term follow up in screen-detected cases.

5 ARE CKD SCREENING PROGRAMMES

COST-EFFECTIVE?
The demonstration of cost-effectiveness of a communitybased targeted screening programme requires the demonstration and proof of clinical benefit in the long term to the
screen-detected person with CKD. Potentially this benefit
may include the avoidance of dialysis or transplant dependence or delay in commencing dialysis treatment and a
reduction in the frequency of cardiovascular morbidity and
mortality. These trials of cost-effectiveness have not yet
been performed. The US KEEP has attempted follow up of
its participants, but the data to date are unclear because of
limited follow up, a low response rate and no costing analysis.29 It is clear that the community screening programmes
such as KEEP or KEY have high infrastructure costs and
arguably attract only those motivated to better health care.
Opportunistic screening in general practice on an annual
basis from age 50 to 69 years for diabetes, hypertension and
proteinuria combined with intensive treatment for those
detected to (or previously known to) have these conditions
was modelled for cost-effectiveness in Australia.16 The key
findings were:
1 The early detection and appropriate management of
high blood pressure, diabetes and protein in the urine
by general practice-based annual screening in 50
69-year-olds (during visits to general practitioners),
along with intensification of management in those
already known to have these conditions, would be
cost-effective and in some cases highly cost-effective.
2 The benefit from such a programme lies in reducing
deaths from heart attacks and kidney failure and in
reducing the number of people needing dialysis or
transplantation.
End-stage kidney failure. For every 1000 people
screened (age from 50 to 69 years) and followed for
their lifetime
High blood pressure screening prevents 11 cases
of kidney failure (requiring dialysis)
Diabetes screening prevents two cases of kidney
failure (requiring dialysis)
Proteinuria screening prevents two cases of
kidney failure (requiring dialysis)

372

Cardiovascular deaths. For every 1000 people

screened (age from 50 to 69 years) and followed
for their lifetime
High blood pressure screening results in 65
fewer deaths from heart attack and vascular
causes
Diabetes screening results in 23 fewer deaths
from heart attack and vascular causes
Proteinuria screening results in 14 fewer deaths
from heart attack and vascular causes
3 In value for money terms (cost per life year saved or
cost per quality-adjusted life year) the CKD-targeted
screening programme is as cost-effective (or in most
cases more cost-effective) than the estimated efficiency of screening programmes (e.g. breast, cervical
and bowel cancer) already available in Australia.
In a US setting a health economic analysis similarly
concluded that screening for nephropathy followed by
optimal antihypertensive therapy with reno-protective
agents in type 2 diabetes and hypertension led to a 44%
reduction in the cumulative incidence of end-stage renal
failure and represented excellent value for money.30
Thus there is a lack of evidence for the cost-effectiveness
of community-based CKD screening but opportunistic
screening in general practice for hypertension, diabetes and
proteinuria appears cost-effective.

6 WHERE TO FOR AUSTRALIA WITH

CKD SCREENING?
The current indications are that general practice-based
opportunistic screening for CKD is an achievable, sustainable and effective means for Australia to pursue early detection and appropriate management of CKD. Eighty-five per
cent of all adult Australians attend a general practitioner at
least once a year thus providing an opportunity for early
detection of kidney disease. This could follow the protocol
proposed by the modelling study16 or focus on just high-risk
individuals such as those known to have diabetes, hypertension and those over the age of 60 years.
Screening programmes mounted in the community
(including the workplace, pharmacies and so on) are costly,
attract clientele who are more likely to want to improve
their health care and rely on a connection back to the
general practitioner to achieve any positive outcome.
However community-based programmes have the advantage of increasing awareness of CKD in the wider population
through associated publicity and provide an opportunity for
health professional education. The sustainability of such
programmes is also an issue with it being unlikely that a
community CKD screening event would recycle to a particular town or region more often than every few years.
The best and most sustainable model and likely the most
cost-efficient appears to be opportunistic general practice
screening. The structure of general practice in Australia is
changing with an increased emphasis on chronic disease
management, preventive health care and a multidisciplinary
team approach. The early detection and best care of CKD

T Mathew and O Corso

readily fits into this mould, given the ease of identification

of the high-risk groups, the simple tests needed to establish
the presence of and the staging of CKD and the overlap of
the action plans for CKD with those for best care of people
with diabetes and cardiovascular risk reduction. However
for this approach to be successful in general practice substantial effort at education is required and the application of
the protocols will need to be made cost-effective for the
practitioner.
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