ACE CLINICAL GUIDANCE Published: 7 October 2022

www.ace-hta.gov.sg

Chronic
kidney
disease
Early detection

Objective Scope Target audience

To enhance timely Identification of patients This clinical guidance is
detection of chronic at increased risk of CKD, relevant to all healthcare
kidney disease (CKD) as well as diagnosis and professionals caring
staging of CKD for patients at risk of
CKD, especially those in
primary care

Chronic kidney disease (CKD) is defined as abnormalities of kidney function or structure persisting for at
least three months, with implications for health.1 In 2017, the estimated global prevalence of CKD was 9.1%.2
In Singapore, the prevalence of CKD among residents aged 18 to 74 years was 8.8% in 2019–2020,3 and CKD has
remained in the top ten causes of death from 2009 to 2019 with CKD-related deaths rising by 76% within that decade.4
Timely CKD detection and management play a major part in slowing down or preventing progression to kidney failure
or other complications. Early detection is particularly significant given that patients are asymptomatic in the early
stages of CKD. Primary healthcare professionals play an essential role in identifying patients at increased risk of
CKD to detect it early.

Statement of Intent
This ACE Clinical Guidance (ACG) provides concise, evidence-based recommendations and serves as a common starting point nationally for
clinical decision-making. It is underpinned by a wide array of considerations contextualised to Singapore, based on best available evidence
at the time of development. The ACG is not exhaustive of the subject matter and does not replace clinical judgement. The recommendations
in the ACG are not mandatory, and the responsibility for making decisions appropriate to the circumstances of the individual patient remains
at all times with the healthcare professional.

Academy of Medicine, Singapore

Chapter of Cardiologists, CPS
Chapter of Endocrinologists, CPS
Chapter of Family Medicine Physicians
Chapter of General Physicians, CPS
Chapter of Geriatricians, CPS
Chapter of Renal Physicians, CPS
2

Identification of patients at increased risk of CKD

Identify patients at increased risk of CKD by assessing their risk

Recommendation 1
factors and determine the need to evaluate for CKD.

Identifying patients at increased risk who will benefit from evaluation for CKD enables timely detection and
management of CKD.1 This involves assessing the patient’s overall risk of CKD, as well as other aspects of the
patient’s health status (for example, their age and frailty) to determine the extent to which they can benefit from
evaluation for CKD.

Key risk factors associated with the overall risk of CKD are listed in Table 1.

Table 1. Risk factors for CKD*

Cardiometabolic risk factors Renal risk factors Other risk factors

Cardiovascular disease Family history of CKD or ESKD Age (especially ≥65 years)
Diabetes mellitus† Hereditary kidney disease Hyperuricaemia or gout
Hypertension† History of AKI Nephrotoxic medications
(including frequent or
Obesity (BMI ≥ 27.5 kg/m2) Recurrent kidney stones chronic NSAID use)
Metabolic syndrome Multi-system diseases that Smoking
impact the kidneys (such as SLE)

AKI, acute kidney injury; BMI, body mass index; CKD, chronic kidney disease; ESKD, end-stage kidney disease; NSAID, non-steroidal anti-
inflammatory drug; SLE, systemic lupus erythematosus
* This table presents more commonly known risk factors for CKD; it is not an exhaustive list. Bolding denotes risk factors that are particularly important for CKD.
†
Including presentations associated with pregnancy.

Cardiovascular disease, diabetes, hypertension, and obesity are particularly important risk factors for CKD (in
bold in Table 1). The cardiometabolic risk inherent in these risk factors, that is, high blood glucose, high blood
pressure, and high BMI─along with related risk factors such as hyperlipidaemia and smoking─are modifiable and
can be managed to reduce the patient’s risk of CKD and associated significant comorbidities or complications,
including cardiovascular mortality.

While recognising risk factors is integral to assessing the patient’s overall risk of CKD, this does not mean that
all patients with CKD risk factors would require evaluation for CKD. For example, evaluation for CKD may be
prudent for a healthy 40-year-old patient with a strong family history of CKD despite their young age, but may not
be warranted for a healthy 40-year-old patient who is a social smoker.

Recommendation 2 starting on page 3 and Recommendation 3 starting on page 5 provide more details on
evaluation for CKD.
3

CKD diagnosis
Diagnose CKD if any of the following is present for at least three months:
• GFR < 60 mL/min/1.73m2
Recommendation 2
• UACR ≥3 mg/mmol (≥30 mg/g)
• Other marker of kidney damage
Evaluation for CKD involves investigating for abnormalities of kidney function or structure in relation to the diagnostic
criteria for CKD as shown above.

Evaluating kidney function─GFR

eGFR equations: MDRD and CKD-EPI
Glomerular filtration rate (GFR) is generally accepted
as the best overall index of kidney function. 1 As The Modification of Diet in Renal Disease
measuring ‘true’ GFR is cumbersome and difficult to (MDRD) and Chronic Kidney Disease
perform accurately, serum creatinine-based estimating Epidemiology Collaboration (CKD-EPI)
equations are commonly used to obtain the estimated equations both estimate GFR based on
GFR (eGFR). GFR is a more sensitive marker for CKD serum creatinine, age, gender, and are
than serum creatinine alone.1,5,6 GFR <60 mL/min/1.73m2 adjusted for body surface area. CKD-EPI is
is internationally accepted as the threshold for CKD, more accurate, particularly at higher
and is associated with increased risk of adverse renal GFR, enabling reporting of numeric values
outcomes (including higher risk of CKD progression, for GFR up to 90 mL/min/1.73m2 (relevant
dialysis, CKD-related death, and AKI), cardiovascular for more detailed staging of CKD─see
and all-cause mortality.7-10 Recommendation 3 starting on page 5).

Acute kidney injury

Acute kidney injury (AKI) is defined as any of the following:11,12

• Increase in serum creatinine of ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 hours
• Increase in serum creatinine ≥1.5 times of baseline, which is known or presumed to have occurred
within the prior 7 days
• Urine volume < 0.5 mL/kg/h for 6 hours
While evaluating patients for CKD, be cognisant of the possibility of AKI. If AKI is suspected, repeat
a serum creatinine test as soon as practicable (other tests may also be required). Patients with
eGFR < 60 mL/min/1.73m2, particularly when AKI is suspected, should have a repeat serum creatinine
as soon as practicable to rule out AKI.

Evaluating kidney damage─UACR or other

Albuminuria threshold
markers of kidney damage
Albuminuria is a common marker of kidney damage, For ease of clinical application and in line with
as albumin is the main protein found in urine in many international consensus, this clinical guidance
presentations of kidney diseases, including CKD resulting adopts a common albuminuria threshold
from diabetes or hypertension. Urine albumin:creatinine of UACR ≥ 3 mg/mmol (≥ 30 mg/g) for both
ratio (UACR) is the recommended measure of albuminuria males and females,1 while acknowledging
instead of urine protein:creatinine ratio (UPCR) because that gender-specific thresholds may still be
UACR is better than UPCR for detecting early progressive used in some practice settings in Singapore.
kidney damage.1,13-15 UACR ≥ 3 mg/mmol (≥ 30 mg/g) Patients should be appropriately tested and
is internationally accepted as the threshold for CKD, followed up whether common or gender-
and is associated with increased risk of adverse renal specific thresholds are used.
outcomes (including higher risk of CKD progression,
dialysis, CKD-related death, and AKI), cardiovascular and
all-cause mortality.7-10

Other markers of kidney damage may be used for diagnostic purposes in addition to, or instead of, albuminuria.
Examples include urine sediment abnormalities (such as casts) and imaging abnormalities (such as hydronephrosis
on ultrasound). A history of kidney transplantation is also considered a marker of kidney damage and immediately
qualifies as CKD (regardless of GFR or UACR levels).
4

Table 2. Key information for ordering and interpreting eGFR and UACR

eGFR UACR

When to repeat Repeat 3 months after the initial test to Repeat 3 months after the initial
the test confirm if patient has CKD (may also be test to confirm if patient has CKD
repeated sooner if clinically indicated). (may also be repeated sooner if
clinically indicated).

Factors that Factors that could increase serum Factors that could increase
could influence creatinine (hence decrease eGFR) albuminuria (hence increase UACR)
the test results include:1,16 include:1,17
(without • High muscle mass • Menstruation
necessarily
• High-protein diet • Urinary tract infection
affecting
kidney • Medications that increase serum • Heavy exercise within last 24 hours
function) creatinine without necessarily • Congestive heart failure
affecting kidney function
(for example, trimethoprim)
Factors that could decrease urine
creatinine (hence increase UACR):1
Factors that could decrease serum
• Female gender
creatinine (hence increase eGFR)
include:1,16 • Older age
• Low muscle mass (for example, patients • Low muscle mass (for example,
with sarcopaenia, paraplegia, amputation, patients with sarcopaenia,
or muscular dystrophy) paraplegia, amputation, or
muscular dystrophy)
• Malnutrition, inflammation, or
deconditioning (for example, patients with
cancer or severe cardiovascular disease,
hospitalised patients)
• Low-protein diet

Practical Advise patient to abstain from high- A 24-hour collection is not necessary.
considerations protein food such as meat for 12 hours
prior to the test.18 An early morning spot urine sample
is preferred as it correlates well with
Patients with eGFR <60 mL/min/1.73m2 24-hour protein excretion, and has
should have a repeat serum creatinine relatively low intra-individual variability.
as soon as practicable to rule out AKI,
particularly when AKI is suspected. A UACR ≥3 mg/mmol (≥30 mg/g)
based on a random urine sample
should be repeated on an early
morning urine sample.

AKI, acute kidney injury; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; UACR, urine albumin:creatinine ratio

Incidental dipstick findings19

During routine health screening, such as annual medical examinations, a urine dipstick test may detect
proteinuria or haematuria. False-positive and false-negative results are not unusual in dipstick urinalysis.
Any findings of concern, for example persistent proteinuria or haematuria, should prompt further
investigations to rule out serious aetiologies.
5

CKD staging

Determine the stage of CKD based on GFR,

Recommendation 3
UACR, and the cause(s) of CKD.
Figure 1. Components of CKD staging

Once CKD is diagnosed, the stage of CKD needs to be determined to

inform prognosis and management. CKD staging is based on cause and
GFR UACR
severity, with the latter reflected by GFR and UACR. This is a shift away
from previous approach where CKD staging only focused on GFR.1 CKD
GFR and UACR are categorised quantitatively, while cause is described staging
qualitatively. All three form essential components of CKD staging.

Cause

GFR continues to be used in CKD staging as the overall marker of the severity of reduced kidney function.

Category Description GFR range (mL/min/1.73m2)‡

G1 Normal or high ≥90
G2 Mildly decreased 60-89
G3a Mildly to moderately decreased 45-59
G3b Moderately to severely decreased 30-44
G4 Severely decreased 15-29
G5 Kidney failure <15

‡
Range based on Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and
Management of Chronic Kidney Disease.1

UACR (measuring albuminuria) is included as another component of CKD staging not only because it is a marker
of kidney damage severity, but also because it is associated with the progression of kidney disease.

UACR range§
Category Description
(mg/mmol) (mg/g)
A1 Normal to mildly increased <3 <30
A2 Moderately increased 3-30 30-300
A3 Severely increased >30 >300

§
Range based on Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and
Management of Chronic Kidney Disease.1

The cause of disease is included as part of CKD staging as it is fundamentally important in prognostication and
choice of cause-specific treatments. The cause of CKD should be established by considering findings from the
patient’s history and physical examination. For many patients, the risk factor(s) prompting evaluation for CKD in
the first place (such as diabetes, hypertension, or family history of CKD) may offer a plausible cause of CKD.
Clinical judgement needs to be exercised regarding whether this provides a sufficient explanation, or whether
further investigations are warranted to determine the cause (or in some cases, additional causes), for example:1
• Complete urinalysis (including urine microscopy) to detect haematuria, pyuria, or casts
• Ultrasound to examine kidney structure
• Serum and urine electrolytes to investigate for renal tubular disorders
6

Unlike GFR and UACR which can be quantified and categorised numerically in CKD staging, cause is described
qualitatively. Collectively, the quantitative (GFR and UACR) and qualitative (cause) components of CKD staging
provide essential information to determine the patient’s prognosis and most appropriate management. The
importance of each component of CKD staging is illustrated through some clinical scenarios in Figure 2 below.

Figure 2. Clinical scenarios illustrating the importance of GFR, UACR, and cause in CKD staging

Despite having the same GFR and UACR categories, patients in scenarios A
and B may have different prognosis and would be managed differently because
of the different causes of their CKD.

Despite having the same

GFR category and CKD
A B
cause, patient in scenario
C has more severe
albuminuria than patient in G3a** A1 G3a** A1

scenario A (as reflected by CKD CKD

the higher UACR category), staging staging
hence patient in scenario C
is expected to: Hypertension Polycystic
and diabetes kidney disease**

• Have a poorer
prognosis (i.e. progress
to kidney failure C D
more quickly without
appropriate management)

• Have a more stringent G3a** A2** G4** A2**

blood pressure target CKD CKD
staging staging

Hypertension Hypertension
and diabetes and diabetes

Despite having the same UACR category and CKD cause, patient in scenario
D has poorer kidney function than patient in scenario C (as reflected by the
higher GFR category), which would lead to different prognosis and selection of
medications for managing CKD or comorbidities.

CKD, chronic kidney disease; GFR, glomerular filtration rate; UACR, urine albumin:creatinine ratio
** Findings present for at least three months which meet CKD diagnostic criteria (see Recommendation 2 on page 3).
7

Management, patient education, and follow-up for patients with CKD

For patients diagnosed with CKD, discuss the diagnosis and

Recommendation 4
management options with the patient.

Once CKD is diagnosed and staged, appropriate management is critical to slow down or prevent progression of
CKD to kidney failure or other complications. Management of CKD (including pharmacotherapy) will be the focus
of a separate clinical guidance.

Patient education and involvement are widely accepted as integral parts of chronic disease management. Increased
patient knowledge about CKD can improve health outcomes.20 Conversely, a patient’s lack of knowledge, passive
attitude towards self-management, and insufficient patient-healthcare professional communication can be barriers
to optimal CKD management.21 Therefore, it is important for healthcare professionals to engage patients with
CKD in a discussion about their diagnosis and management options. Points to include when discussing CKD with
patients should be tailored to the patient’s individual circumstances:

Explaining what CKD is, including current stage of CKD, health implications and likely prognosis.

Reassuring the patient that proper management can slow down the progression of CKD.

Explaining the possible cause(s) and risk factor(s) contributing to the patient’s CKD, and how these can be
further assessed.

Discussing the management options with the patient, including emphasising the importance of managing
modifiable cause(s) and risk factor(s), and optimising management of related comorbidities.

Explaining how medications can help the patient manage some of the cause(s) and risk factor(s), and the
importance of adhering to the medications prescribed.

Explaining how the patient can actively participate in their own care (for example, attend regular follow-up
visits and maintain a healthy lifestyle, including a balanced diet, physical activity, and smoking cessation).

Follow-up for patients at increased risk of but do not have CKD

For patients who do not have CKD but are at increased risk, monitor
Recommendation 5
for CKD regularly.

Patients who are at increased risk but do not have CKD should still be followed up regularly. While all patients at
increased risk of CKD should be followed up at least annually, closer monitoring may be indicated in some cases,
for example when risk factors are poorly controlled.

Referral

Recommendation 6 Referral to a specialist could be made at any point.

Specialist referral could be considered at any point, and is usually indicated for patients who have CKD with:
• GFR <30 mL/min/1.73m2 (GFR categories G4 and G5)1,18,22,23
• Persistent significant albuminuria [UACR category A3 (UACR >30 mg/mmol (>300 mg/g))]1,18,22
• Hypertension refractory to optimised antihypertensive treatment1,18,22,23
• Sustained decline in GFR of >5 mL/min/1.73m2 per year23
• Persistent microscopic haematuria or an episode of gross haematuria
• Known or suspected rare or genetic causes of CKD18,23
• Known or suspected renal artery stenosis1,18,23

The choice of specialist depends on the reason for referral.

References
Expert group

Scan the QR code for the reference

Chairperson
list to this clinical guidance Prof Chan Choong Meng, Nephrology (SGH)

Members
Dr Andrew Ang Teck Wee, Family Medicine, Eunos Polyclinic
(SHP)

Adj Asst Prof Manohar Giliyar Bairy, Nephrology (TTSH)

Dr Daphne Gardner Tan Su-Lyn, Endocrinology (SGH)

Adj Asst Prof Pankaj Kumar Handa, General Medicine (TTSH)

Dr S Suraj Kumar, Family Medicine (Drs Bain and

Partners)

Dr Titus Lau Wai Leong, Nephrology (NUH)

Dr Edwin Lim Boon Howe, Family Medicine (Lakeside Family

Medicine Clinic)

Dr Lim Chee Kong, Family Medicine (NHGP)

Asst Prof Lin Weiqin, Cardiology (NUHCS)

Dr Low Lip Ping, Cardiology (Low Cardiology Clinic)

Dr Sharon Ngoh Hui Lee, Family Medicine (Ang Mo Kio Family

Medicine Clinic)

Dr Sitoh Yih Yiow, Geriatric Medicine (Age-Link Specialist

Clinic for Older Persons)

Dr Abel Soh Wah Ek, Endocrinology (Abel Soh Diabetes,

Thyroid and Endocrine Clinic)

Dr Tan Seng Hoe, Nephrology (SH Tan Kidney and

Medical Clinic)

Dr Cynthia Wong Sze Mun, Family Medicine (National

University Polyclinics)

About the Agency

The Agency for Care Effectiveness (ACE) was established by the Ministry of Health (Singapore) to drive better decision-making in healthcare
by conducting health technology assessments (HTA), publishing healthcare guidance and providing education. ACE develops ACE Clinical
Guidances (ACGs) to inform specific areas of clinical practice. ACGs are usually reviewed around five years after publication, or earlier, if new
evidence emerges that requires substantive changes to the recommendations. To access this ACG online, along with other ACGs published
to date, please visit www.ace-hta.gov.sg/acg

Find out more about ACE at www.ace-hta.gov.sg/about-us

© Agency for Care Effectiveness, Ministry of Health, Republic of Singapore

All rights reserved. Reproduction of this publication in whole or in part in any material form is prohibited without the prior written permission of the
copyright holder. Application to reproduce any part of this publication should be addressed to: ACE_HTA@moh.gov.sg

Suggested citation:
Agency for Care Effectiveness (ACE). Chronic kidney disease – early detection. ACE Clinical Guidance (ACG), Ministry of Health, Singapore. 2022.
Available from: go.gov.sg/acg-chronic-kidney-disease-early-detection

The Ministry of Health, Singapore disclaims any and all liability to any party for any direct, indirect, implied, punitive or other consequential damages arising directly or
indirectly from any use of this ACG, which is provided as is, without warranties.

Agency for Care Effectiveness (ACE)

College of Medicine Building
16 College Road Singapore 169854

Agency for Care Effectiveness - ACE Agency for Care Effectiveness (ACE) Driving better decision-making in healthcare