Chronic Kidney Disease

Chronic kidney disease
Straight to the point of care
Last updated: Sep 13, 2022

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 5
Case history 6
Diagnosis 7
Approach 7
History and exam 8
Risk factors 9
Investigations 12
Differentials 14
Criteria 16
Screening 16
Management 17
Approach 17
Treatment algorithm overview 23
Treatment algorithm 25
Emerging 59
Primary prevention 59
Secondary prevention 59
Patient discussions 60
Follow up 61
Monitoring 61
Complications 62
Prognosis 63
Guidelines 65
Diagnostic guidelines 65
Treatment guidelines 66
Online resources 68
Evidence tables 69
References 72
Disclaimer 87
Chronic kidney disease Overview
Summary
Chronic kidney disease (CKD) is a common condition that is often unrecognised until the most advanced
stages.
OVERVIEW
Diagnosis is determined only by laboratory studies: proteinuria or haematuria, and/or a reduction in the
glomerular filtration rate, for more than 3 months' duration.
The most common causes are diabetes mellitus and hypertension.
Glycaemic control for diabetic kidney disease and optimisation of blood pressures are key in slowing the
progression of the disease. Use of agents that block the renin-angiotensin system and sodium-glucose co-
transporter 2 inhibitors have kidney function preserving benefits that are independent of blood pressure and
glucose control.
CKD is a risk factor for cardiovascular disease, independent of comorbidities such as diabetes, hypertension,
and dyslipidaemia.
Definition
Chronic kidney disease (CKD), also known as chronic renal failure, is defined as abnormalities of kidney
structure or function, present for ≥3 months, with implications for health.[1] This means a glomerular filtration
rate less than 60 mL/minute/1.73 m², or the presence of one or more of the following markers of kidney
damage: albuminuria/proteinuria, urine sediment abnormalities (e.g., haematuria), electrolyte abnormalities
due to tubular disorders, abnormalities detected by histology, structural abnormalities detected by imaging, or
history of kidney transplantation.[1]
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Chronic kidney disease Theory
Epidemiology
Chronic kidney disease (CKD) is a common condition that is often unrecognised until the most advanced
stages. It is estimated that 9% to 13% of the adult population worldwide has CKD.[3] [4] [5] In 2017, the
THEORY
estimated worldwide prevalence of CKD stages 1 to 2 accounted for 5%, stage 3 for 3.9%, stage 4 for 0.16%,
stage 5 for 0.07%, dialysis for 0.041%, and kidney transplantation for 0.011%.[5] The global prevalence
of CKD is rising and is thought to be due to an ageing population; a higher incidence of diseases such as
diabetes and hypertension, which are the most common causes in the adult population; and an increased
incidence of glomerular disorders such as focal segmental glomerulosclerosis.[4] [6] [7] Black people,
Hispanic people, and those with a family member who has a diagnosis of kidney disease have a higher
prevalence than the general population.[8] [9] Additionally, individuals with an episode of acute kidney injury
are most likely to be at risk for chronic kidney injury and end-stage kidney disease in the future.[10]
CKD is a condition associated with high racial and socioeconomic disparities. In 2016, the age-standardised
incidence of end-stage renal disease was almost threefold higher among black people compared with
white people in the US, whereas data from the ACCORD study revealed that race was not associated
with accelerated development and progression of CKD in participants who received standardised medical
care.[11] The results suggest that equitable health care delivery for patients with diabetes may reduce racial
disparities in diabetes-associated CKD.
Aetiology
The most common cause in the adult population is diabetes.[6] It is estimated that one third of patients with
diabetes will develop kidney disease, as defined by albuminuria and/or a reduction in the glomerular filtration
rate within 15 years after the diagnosis of diabetes.[12] [13]
Hypertension is the second most common cause.[6] The interaction between hypertension and CKD is
complex, with hypertension a cause and a consequence of CKD.[14]
Often people are given the diagnosis of hypertensive renal disease if no other identifiable aetiology is
evident.
Less frequent causes include cystic disorders of the kidney (polycystic kidney disease), obstructive uropathy,
glomerular nephrotic and nephritic syndromes such as focal segmental glomerulosclerosis, membranous
nephropathy, lupus nephritis, amyloidosis, and rapidly progressive glomerulonephritis.[1]
Around one third of adults with CKD have a positive family history of CKD, which suggests genetic
causation.[15]
Climate also plays a significant role in some CKD presentations.[16] Heat stress nephropathy may represent
one of the first epidemics due to global warming. Various presentations in different parts of the world, such
as Mesoamerican nephropathy, Sri Lankan nephropathy, and CKD of unknown origin (CKDu), may all be
related to the climate.[17] The mechanisms implicated are hyperthermia, dehydration, and toxin and heavy
metal concentration in drinking water and soil, in addition to worsening poverty with climate change leading
to poor harvests.[16] [17]
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Sep 13, 2022.
Pathophysiology
The pathophysiology is complex. Regardless of the method of renal injury (i.e., diabetes, hypertension, or
glomerular disorders), once renal damage has occurred, a cascade of events ensues.[18] [19]
THEORY
• In response to renal injury, there is thought to be an increase in intra-glomerular pressure with
glomerular hypertrophy, as the kidney attempts to adapt to nephron loss to maintain constant
glomerular filtration.
• An increase in glomerular permeability to macro-molecules such as transforming growth factor-beta
(TGF-beta), fatty acids, pro-inflammatory markers of oxidant stress, and protein may result in toxicity
to the mesangial matrix, causing mesangial cell expansion, inflammation, fibrosis, and glomerular
scarring.
• Additionally, renal injury results in an increase in angiotensin II production, causing an upregulation of
TGF-beta, contributing to collagen synthesis and renal scarring within the glomerulus.
• Both the structural alterations and accompanying biochemical, cellular, and molecular changes seem
to account for progressive renal scarring and loss of kidney function.
• All forms of CKD are also associated with tubulo-interstitial diseases; the exact mechanism of injury is
not known, but is thought to be secondary to a reduction in blood supply in addition to an infiltration of
lymphocytes and inflammatory mediators that result in interstitial fibrosis and tubular atrophy.
Classification
Kidney Disease: Improving Global Outcomes (KDIGO)
classification[1]
KDIGO classifies CKD based on cause (C), glomerular filtration rate category (G), and albuminuria category
(A).
• Cause is ascertained from history (e.g., diabetic kidney disease, hypertensive nephrosclerosis).
• Glomerular filtration rate (GFR) category is based on GFR (mL/minute/1.73 m²):
• G1 GFR ≥90: normal or high

• G2 GFR 60 to 89: mildly decreased
• G3a GFR 45 to 59: mildly to moderately decreased
• G3b GFR 30 to 44: moderately to severely decreased
• G4 GFR 15 to 29: severely decreased
• G5 GFR <15: kidney failure.
• Albuminuria category is based on albumin excretion rate (AER) or albumin to creatinine ratio (ACR):
• A1 AER <30 mg albumin/24 hours or ACR <3 mg/mmol (<30 mg/g): normal to mildly increased
• A2 AER 30 to 300 mg albumin/24 hours or ACR of 3 to 30 mg/mmol (30 to 300 mg/g):
moderately increased
• A3 AER >300 mg albumin/24 hours or ACR >30 mg/mmol (>300 mg/g): severely increased.
There is substantial existing literature using the term microalbuminuria; however, the KDIGO work group
encourages the adoption of the term 'albuminuria', with subsequent quantification of the level or amount.[1]
5
A urine ACR >220 mg/mmol (>2200 mg/g) may be accompanied by signs and symptoms of nephrotic
syndrome (e.g., low serum albumin, oedema, and high serum cholesterol).[1]
However, nephrotic level proteinuria is conventionally defined as >3.5 g proteinuria per 24 hours.[2]
THEORY
Case history
Case history #1
A 54-year-old man with a 10-year history of diabetes and hypertension, with complications of diabetic
retinopathy and peripheral neuropathy, presents to his primary care physician with complaints of fatigue
and weight gain of 4.5 kg over the past 3 months. He denies any changes in his diet or glycaemic
control but does state that he has some intermittent nausea and anorexia. He states that he has noticed
that his legs are more swollen at the end of the day but improve with elevation and rest. Physical
examination reveals an obese man with a sitting blood pressure of 158/92 mmHg. The only pertinent
physical examination findings are cotton wool patches and micro-aneurysms bilaterally on fundoscopic
examination and pitting, bilateral lower-extremity oedema.
Other presentations
Chronic kidney disease presents insidiously over months with vague complaints of fatigue, mild reduction
in appetite, and, at more advanced stages, nausea and anorexia. Oedema is a common presentation -
as the glomerular filtration rate declines, there is an inability to effectively excrete salt and water to remain
in metabolic balance with dietary intake. Additionally, proteinuria with a decrease in serum albumin may
contribute to the development of peripheral oedema.[3]
Chronic kidney disease Diagnosis
Approach
It is important to note that a significant proportion of people are asymptomatic, and the diagnosis relies on
pathological evidence of kidney damage such as haematuria and/or proteinuria, or laboratory evidence of a
reduction in the glomerular filtration rate (GFR) with an elevated serum creatinine.
History
Signs and symptoms are often vague, including fatigue (which may be related to uraemia or the anaemia
associated with CKD), nausea, and possibly the development of oedema. Uraemic illness is due largely
to the accumulation of organic waste products that are normally cleared by the kidneys, and symptoms
may be present to some degree in the early stages of kidney failure.[44] As kidney failure progresses to
the more advanced stages of uraemia, patients will often describe anorexia, nausea, vomiting, restless
legs, pruritus, and overall not feeling well.[45] If patients begin to have a lack of urine production, then
the resulting fluid overload may be present with dyspnoea and orthopnoea due to pulmonary oedema.
Cognition may be affected in all stages of CKD.[3] In the most advanced stages of uraemia, patients may
present with seizures or coma.[46]
Examination
Signs as a consequence of CKD are hypertension, peripheral oedema (due to sodium retention and
exacerbated by hypoalbuminaemia), and pallor due to anaemia.[3] Physical examination findings are also
directed towards the discovery of end-organ damage associated with causative disease states such as
diabetes or hypertension, which cause CKD. A fundoscopic eye examination is critical for the diagnosis
of diabetic or hypertensive retinopathy as evidence of microvascular damage that has probably occurred
in the kidney, resulting in CKD. In men, a rectal examination for prostatic enlargement or for the diagnosis
of prostate nodules can be helpful in determining a diagnosis of obstructive uropathy. In glomerular
nephrotic and nephritic syndromes, the signs and symptoms of CKD may present more acutely with
accelerated hypertension, peri-orbital and peripheral oedema, rashes, or arthritis on musculoskeletal
examination for patients with autoimmune disorders.[47] Patients may describe their urine as foamy if
significant proteinuria is present, or tea- or cola-coloured in the setting of haematuria.
DIAGNOSIS
Initial investigations
Most people are unaware that they have CKD and are informed only after abnormalities are discovered
by blood and/or urine tests.[3] The first diagnostic tests to order are a serum creatinine (as part of renal
chemistry), estimated GFR (with consideration of serum cystatin-C in people with extremes of muscle
mass), and urinalysis to assess for haematuria and proteinuria.[1] [3] For the diagnosis of CKD, urinary
albumin assessment is usually preferred to that of total urine protein with calculation of the albumin
excretion rate (AER) or the albumin to creatinine ratio (ACR).[1] [48] However, nephrotic level proteinuria
is conventionally defined as >3.5 g proteinuria per 24 hours.[2]
Proteinuria is both a diagnostic and a prognostic variable in the evaluation of patients with CKD.[3] [49]
Renal ultrasound is required to evaluate kidney size, mass lesions, urinary tract obstruction, and, with a
duplex examination, renal arterial flow.[3] [50]
Additional investigations
Kidney biopsies are performed in a minority of patients with CKD.[1] A kidney biopsy to determine a
pathological diagnosis is indicated if a glomerular nephrotic or nephritic syndrome is suspected, or in
7
people with diabetes with atypical presentations such as rapidly progressive kidney failure. Nephrotic
syndrome may be suggested by proteinuria, and both nephritic and nephrotic syndromes may be
suggested by severe presenting symptoms (accelerated hypertension, periorbital and peripheral oedema)
or with symptoms of underlying autoimmune diseases (rashes or arthritis). Certain infections, such as
hepatitis B and C, syphilis, and streptococcal pharyngitis are associated with glomerular disorders. A
kidney biopsy is critical in these cases to determine the correct diagnosis.[2]
Imaging of the genitourinary tract may be helpful in the evaluation of a patient with CKD. Plain abdominal
x-ray is a non-specific test that may aid in the detection of calcium-containing kidney stones. Other
radiological tests, such as an abdominal computed tomography, are reserved for evaluation of stone
disease and further characterisation of renal cystic or mass lesions. Magnetic resonance imaging is
reserved for renal mass lesions such as renal cell carcinoma.
History and exam

Key diagnostic factors
presence of risk factors (common)
• Risk factors include age >50 years, male sex, black or Hispanic ethnicity, family history, smoking,
obesity, long-term analgesic use, diabetes, hypertension, and autoimmune disorders.
fatigue (common)
• Signs and symptoms of CKD are often vague and commonly include fatigue, which may be due to
uraemia or anaemia.[44] Anaemia is associated with CKD due to the lack of erythropoietin produced
by the kidney, usually once the glomerular filtration rate declines to <50 mL/minute/1.73 m².[3] There
can also be other deficiency anaemias (e.g., iron) that manifest during the assessment of CKD.
oedema (common)
DIAGNOSIS
• Periorbital and peripheral oedema develop as a result of salt and water retention as the glomerular
filtration rate declines, and may be exacerbated by hypoalbuminaemia.[3]
nausea with/without vomiting (common)

• Thought to be due to an accumulation of toxic waste products in the circulation, such as urea that is
not excreted by the kidney. As kidney failure progresses to the more advanced stages of uraemia,
patients may report vomiting. They may also report a metallic taste in the mouth further worsening the
nausea.
pruritus (common)
• Thought to be due to an accumulation of toxic waste products in the circulation and under the skin,
such as urea that is not excreted by the kidney.[44]
restless legs (common)

• A symptom of uraemia.[44] Present in all stages of CKD.[51]
anorexia (common)
• Thought to be due to an accumulation of toxic waste products in the circulation, such as urea that is
not excreted by the kidney.
infection-related glomerular disease (uncommon)

• Infections such as hepatitis B and C, syphilis, and streptococcal pharyngitis are associated with
glomerular disorders.
• A kidney biopsy is critical in these cases to determine the correct diagnosis.[2]
Other diagnostic factors

arthralgia (common)
• If the patient has concomitant autoimmune disorder.
enlarged prostate gland (common)

• Prostate examination in men should be performed to exclude obstructive uropathy.
foamy-appearing urine (uncommon)

• Indicative of proteinuria.
cola-coloured urine (uncommon)

• Indicative of haematuria.
rashes (uncommon)
• Ecchymosis and purpura are signs of haematological consequences of CKD.
• The patient may have a concomitant autoimmune disorder: for example, systemic lupus erythematosus
and butterfly rash.
dyspnoea (uncommon)
DIAGNOSIS
• Associated with pulmonary oedema due to reduced urine output in worsening disease.
orthopnoea (uncommon)
• Associated with pulmonary oedema due to reduced urine output in worsening disease.
seizures (uncommon)
• Occurs in advanced-stage disease.[46]
• Thought to be due to an increase in neurotoxins that are not excreted by the kidney.
retinopathy (uncommon)
• Fundoscopy is a key examination in determining the presence of diabetic or hypertensive retinopathy,
as evidence of microvascular damage, which occurs in uncontrolled diabetes/hypertension. Diabetic
and hypertensive patients should be screened for such changes.
Risk factors
Strong
9
diabetes mellitus
• This is the most common cause.[6]
• It is estimated that approximately 20% to 40% of people with diabetes will have CKD, as documented
by albuminuria and/or a reduction in the glomerular filtration rate, within 15 years of diagnosis.[12] [13]
CKD rarely develops in patients with type 1 diabetes before 10 years following diagnosis, whereas
CKD is present at time of diagnosis in around 3% of patients with type 2 diabetes.[13]
• Glycaemic control directly correlates with the development of diabetic kidney disease and the rapidity
of progression to end-stage renal disease.[12]
• Hyperglycaemia results in formation of advanced glycated end products.[20] This leads to mesangial
oxidative stress, which results in matrix expansion and increased vascular permeability, which in
turn attracts inflammatory mediators.[21] These promote collagen production, leading to glomerular
sclerosis.
hypertension
• This is the second most common cause of CKD.[6]
• Hypertension is also a consequence of CKD (including from other causes such as diabetic kidney
disease, and glomerular nephrotic and nephritic syndrome), and contributes to its progression to end-
stage renal disease.[14]
• Hypertension is thought to affect both the vasculature and tubulo-interstitial components of the kidney,
resulting in ischaemic damage from arterial narrowing. The end result is loss of nephron mass, and
atrophy and fibrosis of the tubules and interstitium.
age >50 years

• Older age is a key predictor of CKD. Healthy ageing is associated with structural changes in the
kidney and a decrease in glomerular filtration rate (GFR).[22] Typically the GFR declines by 0.75
mL/minute/1.73 m² per year in healthy ageing, but urine albumin excretion does not change, thus,
the increase in the prevalence of criteria-defined CKD in healthy older adults is due more to a GFR
decline than to increasing albuminuria and has a much lower risk of progression to end-stage renal
disease.[22] However, increasing age is associated with an increased likelihood of comorbid conditions
DIAGNOSIS
that are risk factors for CKD, such as diabetes, hypertension, and cardiovascular disease.[23]
childhood kidney disease

• A history of childhood kidney disease is a risk factor for adult CKD and end-stage renal disease
(ESRD). Children with a medical history of congenital anomalies, glomerular disease, or pyelonephritis
with normal kidney function and blood pressure have a four-fold increased risk for ESRD as compared
to children without kidney disease.[24]
Weak
smoking
• Smoking has been associated as a risk factor for the development and progression of the disease,
probably because of accelerated atherosclerosis and vascular disease, as well as exacerbating
underlying hypertension.[25] [26]
obesity
• Obesity is an associated risk factor.[27] It may contribute to the development of diabetes, exacerbate
poor control of hypertension, contribute to renal ischaemia and hypertension with associated sleep
apnoea, and cause glomerular strain with hypertrophy and glomerulosclerosis.[28]
black or Hispanic ethnicity

• Black or Hispanic people are at higher risk than white people.[29] [30] The mechanism is not known,
but is thought to be due in part to a higher incidence of diseases such as diabetes and hypertension
in these populations. Additionally, in black and Hispanic populations, genetic factors such as
apolipoprotein L1 risk variants increase the risk for non-diabetic kidney disease.[31]
family history of CKD

• People with a close family member with the disease are at a higher risk themselves of developing
CKD.[9] [15] The mechanism is thought to be due in part to genetic susceptibility to certain disease
states, such as diabetes, hypertension, polycystic kidney disease, Alport syndrome, and possibly
glomerular syndromes, such as IgA nephropathy and focal segmental glomerulosclerosis.
autoimmune disorders
• Autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and
Sjogren syndrome may cause glomerular or tubulo-interstitial CKD.[32] [33]
male sex
• Men are at a higher risk of CKD progression than women.[34]
• The mechanism of renal injury is not known but is thought to be related to differences in sex hormones
and the differential effect of sex on lifestyle and traditional risk factors.[34]
long-term use of non-steroidal anti-inflammatory drugs

• Long-term use of anti-inflammatory analgesics for rheumatological disorders and pain control have
been associated with the development of CKD.[35] [36] Non-steroidal anti-inflammatory drugs, and
DIAGNOSIS
previously phenacetin, have been described as causing analgesic nephropathy.
high uric acid levels

• There is an expected increase in uric acid levels with advancing CKD. Literature also discusses
uric acid as a contributory factor to CKD worsening.[37] [38] [39] However, trials of urate-lowering
treatment did not result in clinically meaningful benefits to kidney outcomes.[40] [41]
11
Investigations
1st test to order
Test Result
renal chemistry elevated serum
creatinine; electrolyte
• Includes sodium, potassium, chloride, bicarbonate, urea, creatinine,
abnormalities
and glucose.
• Serum creatinine alone is insufficient to determine CKD and may
be falsely low in conditions of low muscle mass, as in older or
malnourished people, or patients with liver failure.
• Normal creatinine in men is 70 to 120 micromol/L (0.8 to 1.4 mg/
dL), and in women 50 to 97 micromol/L (0.6 to 1.1 mg/dL). However,
there is significant variation due to calibration methods between
laboratories.[3]
• Electrolyte abnormalities may indicate an underlying cause of CKD,
such as tubular disorders.[1] Adaptations in acid excretion by the
kidneys initially prevent a fall in serum bicarbonate concentration, but
as GFR declines, metabolic acidosis develops.[1]
estimation of GFR <60 mL/minute/1.73 m²
• A GFR estimating equation using serum creatinine is recommended
for initial assessment.
• Determines more accurately, by mathematical equations such as
Cockcroft-Gault, the Modification of Diet in Renal Disease Formula,
or the CKD EPI equation, the GFR and the severity and stage of
CKD.[52]
• Formulas have not been proven to be reliable estimators in patients
with a GFR >59 mL/minute/1.73 m².[1]
serum cystatin C and cystatin C-based estimation of GFR reduced muscle mass will
• Warranted in specific circumstances when GFR estimates based on lead to overestimation;
serum creatinine are thought to be inaccurate, such as in people with increased muscle mass
to underestimation of the
extremes of muscle mass (e.g., bodybuilders, people with muscle-
DIAGNOSIS
wasting disorders, older or malnourished people).[1] GFR
urinalysis haematuria and/or

proteinuria
• Screening test to determine for pathological markers of kidney
damage excreted in the urine.
urinary albumin moderately increased
(AER 30-300 mg/day; ACR
• Classification of CKD requires quantification of urinary albumin as
30-300 mg/g)
based on albumin excretion rate (AER) or albumin to creatinine ratio
(ACR).[1] [48] Moderately increased albuminuria is a risk factor for
the development of progressive CKD and coronary artery disease
associated with diabetes and hypertension. Indicated in patients with
diabetes and CKD if there was no evidence of proteinuria on urine
dipstick.[53]
renal ultrasound small kidney size;
presence of obstruction/
• Helps to diagnose CKD if kidney atrophy is present and diagnoses
hydronephrosis; kidney
obstruction with hydronephrosis or bladder retention.[3] [50]
stones
Other tests to consider
Test Result
kidney biopsy variable depending on
aetiology
• Helps to determine pathological diagnosis of CKD in glomerular
nephrotic and nephritic syndromes, and in people with diabetes with
atypical presentations such as rapidly progressive kidney failure.
Also essential in determining whether pathological lesions are due
to infection (e.g., hepatitis B and C, syphilis, and streptococcal
pharyngitis). Provides insight into treatment options based on severity
or chronicity of scarring of glomeruli and interstitium.
plain abdominal radiograph may reveal calcium-
containing kidney stones
• Non-specific test that may aid in the detection of calcium-containing
kidney stones, as medicine and urate stones are not apparent on
plain radiography.
abdominal CT may reveal kidney stones,
renal masses, or cysts
• Imaging test that is helpful to determine the presence or absence
of kidney stones and confirms obstructive component. It is also
helpful to further evaluate cystic lesions or mass lesions in the
kidney. Intravenous contrast is used with caution in high-risk patients,
such as those with CKD with a reduction in the estimated GFR <60
mL/minute, as it can cause acute kidney injury. Prophylaxis with
intravenous normal saline may be indicated or considered in some
patients.[54]
abdominal MRI may reveal mass lesions
in the kidney
• Imaging test that further characterises mass lesions in the kidney,
such as renal cell carcinoma.
• Gadolinium-based MRI examinations have been associated with
nephrogenic systemic fibrosis in patients with kidney disease.
However, not all gadolinium-containing contrast agents have the
same risk of nephrogenic systemic fibrosis, and the benefits of
gadolinium-based MRI use may exceed its risk.[55]
DIAGNOSIS
13
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Diabetic kidney disease • History of poorly controlled • HbA1c is typically >53 mmol/
diabetes for about 10 years. mol (>7%).
Often with co-existing • Diagnostic tests include
diabetic retinopathy and urinalysis for albuminuria
other stigmata of diabetic and a serum creatinine for
microvascular disease. GFR assessment.
• The quantification of
proteinuria is variable over
time and will decrease as the
GFR declines.
• Urine albumin is key for the
diagnosis of early diabetic
kidney disease.
• Kidney ultrasound will
typically show small, atrophic
kidneys only in late stages of
the disease, once substantial
renal injury occurs.
Hypertensive • History of poorly controlled • Diagnostic tests include

nephrosclerosis hypertension for years. More urinalysis for microalbumin
common in black people or protein and a serum
than white people. creatinine for GFR
assessment.
• The urine sediment is
described as bland without
formed elements or
haematuria. Quantification of
proteinuria is <2 g/24 hours.
• Kidney ultrasound typically
DIAGNOSIS
reveals small, atrophic

kidneys.
Ischaemic nephropathy • History of long-standing • The urine sediment is

essential hypertension that is described as bland,
suddenly uncontrolled. More without formed elements or
common in white people and haematuria. Quantification of
older people. proteinuria is <2 g/24 hours.
• Often will have a history of • Kidney ultrasound reveals
atherosclerotic disease such asymmetrical kidney size
as coronary artery disease of ≥2.5 cm with unilateral
or peripheral vascular disease, and duplex scan
disease. There is also a demonstrates an increase
history of tobacco abuse and in the resistive index,
hyperlipidaemia. suggesting obstruction.
• ACE inhibitor renogram,
CT angiogram, magnetic
resonance angiogram,
or renal arteriogram (test
of choice) demonstrates
luminal narrowing of the
renal artery.

symptoms
Obstructive uropathy • More common in men and • Kidney ultrasound is the
older people. Often due to diagnostic test of choice
prostatic enlargement or to document kidney
cancer. obstruction. It would show
• Typical symptoms include hydronephrosis, and
urinary frequency, hesitancy, there may also be post-
inability to empty the bladder void residual volume in
completely, and decrease in those cases when there
urinary stream. is obstruction to bladder
• Urinary tract infections may outflow.
develop.
• Rectal examination may
reveal prostatic enlargement
or nodules.
Nephrotic syndrome • Often associated with a • Laboratory evidence may

more sudden onset of reveal hypoalbuminaemia,
hypertension, or acceleration hyperlipidaemia and an
of essential hypertension increase in serum creatinine.
and development of Urinalysis has proteinuria as
periorbital and peripheral defined at >3.5 g/24 hours.
oedema. • A kidney biopsy is required
to determine the pathological
lesion for nephrotic
syndrome.
• Serological tests for
secondary causes of
nephrotic syndrome
such as anti-nuclear
antibody in systemic
lupus erythematosus,
HIV in focal segmental
glomerulosclerosis, and
DIAGNOSIS
hepatitis B and C in
membranous nephropathy,
and serum protein
electrophoresis for
amyloidosis, are often helpful
in confirming the diagnosis
of the nephrotic syndrome.
Glomerulonephritis • Often associated with • Laboratory evidence

a sudden onset of reveals an increased serum
hypertension or acceleration creatinine, and urinalysis is
of essential hypertension. significant for haematuria
• Patients with autoimmune and proteinuria.
disorders may have a • Urine sediment is evaluated
skin rash or arthritis; post- for the presence of
infectious glomerulonephritis dysmorphic red blood cells
has a recent history of a (RBC) and RBC casts,
pharyngeal or cutaneous which are diagnostic of
infection; bloody diarrhoea is glomerulonephritis.
associated with haemolytic • Serological tests such
uraemic syndrome. as antinuclear antibody,
complement levels, hepatitis
15

symptoms
B and C antibodies, anti-
neutrophil cytoplasmic
antibody, anti-glomerular
basement antibody,
and anti-streptolysin O
titre are often helpful in
confirming the diagnosis of
glomerulonephritis.
• A kidney biopsy is required
to confirm the pathological
lesion of glomerulonephritis.
Criteria
Diagnostic classification[1]
CKD is divided into 6 distinct categories based on glomerular filtration rate (GFR). The GFR category (G1-
G5) has the same GFR thresholds as the CKD stages 1 to 5 recommended previously, as follows:[1]
• G1: GFR >90 mL/minute/1.73 m², and evidence of kidney damage based on pathological diagnosis,
abnormalities of radiographic imaging, or laboratory findings such as haematuria and/or proteinuria
• G2 GFR 60 to 89: mL/minute/1.73 m²
• G3a GFR 45 to 59: mL/minute/1.73 m²
• G3b GFR 30 to 44: mL/minute/1.73 m²
• G4 GFR 15 to 29: mL/minute/1.73 m²
• G5 GFR <15: mL/minute/1.73 m².
The albumin category is also documented based on albumin excretion rate (AER) or albumin to creatinine
ratio (ACR):
DIAGNOSIS
• A1 AER <30 mg albumin/24 hours or ACR <3 mg/mmol (<30 mg/g): normal to mildly increased
• A2 AER 30 to 300 mg albumin/24 hours or ACR of 3 to 30 mg/mmol (30 to 300 mg/g): moderately
increased
• A3 AER >300 mg albumin/24 hours or ACR >30 mg/mmol (>300 mg/g): severely increased.
Screening
There are no established screening guidelines for the general population for CKD. However, based on expert
opinion, there are recommendations to screen those considered high-risk and include all individuals with
diabetes and hypertension aged <50 years, and all of those aged >50 years, with an annual urinalysis and
serum creatinine. Other high-risk populations, such as those with a family history of kidney disease, should
also be considered in the screening programme.[56]
Patients with risk factors for CKD such as diabetes, hypertension, or a family member with CKD should be
evaluated annually with serum creatinine and mathematical formulation for estimation of the glomerular
filtration rate in addition to urinalysis for haematuria and/or proteinuria.
Chronic kidney disease Management
Approach
For updates on diagnosis and management of coexisting conditions during the pandemic, see our topic
'Management of coexisting conditions in the context of COVID-19'.
All aetiologies of CKD are progressive. The main goal of treatment is to slow the progressive loss of kidney
function and prevent the need for renal replacement therapy or kidney transplantation.
It is important to identify patients early in the course of their disease and classify the stage of CKD (GFR
category G1-G5) so that risk factor modification can ensue and identification of comorbidities such as
anaemia and secondary hyperparathyroidism may be treated.
CKD is divided into 6 distinct categories based on glomerular filtration rate (GFR). The GFR category (G1-
G5) has the same GFR thresholds as the CKD stages 1 to 5 recommended previously:[1]
• G1: GFR >90 mL/minute/1.73 m², and evidence of kidney damage based on pathological diagnosis,
abnormalities of radiographic imaging, or laboratory findings such as haematuria and/or proteinuria
• G2: GFR of 60 to 89 mL/minute/1.73 m²
• G3a: GFR of 45 to 59 mL/minute/1.73 m²
• G3b: GFR of 30 to 44 mL/minute/1.73 m²
• G4: GFR of 15 to 29 mL/minute/1.73 m²
• G5: GFR <15 mL/minute/1.73 m².
GFR category G1 to G4 first-line therapy

Several classes of agents have been shown to slow CKD progression. Renin-angiotensin system
blockade and sodium-glucose co-transporter 2 (SGLT2) inhibitors (e.g., empagliflozin, canagliflozin,
dapagliflozin) can preserve kidney function by reducing intra-glomerular pressure independently of blood
pressure (BP) and glucose control.[57] [58] [59]
The DAPA-CKD trial on dapagliflozin included adults with CKD (GFR category G2-G4, estimated GFR
25-75 mL/minute/1.73 m²), with or without type 2 diabetes, and confirmed that the renoprotective effects
of dapaglifozin were independent of diabetes status.[60] In this trial, 97% of participants were taking an
ACE inhibitor or an angiotensin-II receptor antagonist.[60] Dapagliflozin has been approved in Europe and
the US for the treatment of CKD in adults at risk of progression (to reduce the risk of sustained estimated
GFR [eGFR] decline, end-stage kidney disease, cardiovascular death, and hospitalisation for heart
failure).
The major cause of death for patients with CKD is cardiovascular disease. Therefore, treatment of
cardiovascular risk factors, such as optimising glycaemic control, optimising BP with an ACE inhibitor
or an angiotensin-II receptor antagonist, introducing lipid-lowering agents (e.g., statins, ezetimibe), and
reducing proteinuria is recommended.[61] [62] [63]
Diabetes
MANAGEMENT
• Glycaemic goals should be individualised. For many patients, the goal of HbA1c <7% is
appropriate. However, HbA1c 7.0% to 7.9% may be more appropriate in some patients, such
as those with advanced age, limited life expectancy, known cardiovascular disease, high risk of
severe hypoglycaemia, or difficulty achieving lower HbA1c goals despite the use of multiple anti-
17
hyperglycaemic medications and insulin.[20] [64] In patients with diabetes and CKD, there is a
risk for hypoglycaemia because of impaired kidney clearance of medications, such as insulin
(two-thirds of insulin is degraded by the kidney) or sulfonylureas, and because of impaired kidney
gluconeogenesis.
• Patients with type 1 diabetes require treatment with insulin, regardless of whether they are on
dialysis or not.
• In patients with type 2 diabetes, some specific anti-hyperglycaemic medications significantly reduce
all-cause or cardiovascular mortality, or major cardiovascular events or renal complications in some
patient subgroups, and may be considered independently of HbA1c targets.[57] [65] [66] [67]
• There is evidence that the use of SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin)
prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in
people with type 2 diabetes.[68] [60] SGLT2 inhibitors, in addition to reducing hyperglycaemia, have
renal benefits through independent effects on renal tubular glucose reabsorption, weight, BP, intra-
glomerular pressure, albuminuria, and slowed GFR loss.[69] [70]
• The use of SGLT2 inhibitors is not generally recommended in patients with an eGFR of <45 mL/
minute/1.73 m² (<60 mL/minute/1.73 m² for ertugliflozin); however, the CREDENCE trial included
patients with an eGFR 30 to 90 mL/minute/1.73m² and demonstrated a decreased risk of kidney
failure and cardiovascular events.[71] Use of SGLT2 inhibitors is contraindicated in patients with an
eGFR of <30 mL/minute/1.73 m², including patients with end-stage renal disease (ESRD) who are
on dialysis.
• As a class of drugs, glucagon-like peptide-1 (GLP-1) agonists have beneficial effects on
cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.[72] Experience with
GLP-1 agonists in patients with renal dysfunction is limited; therefore, these agents should be used
with caution.[73] Liraglutide, albiglutide, dulaglutide, and semaglutide are not renally excreted and
are the preferred agents in this class.
• Studies report that dipeptidyl peptidase-4 (DPP-4) inhibitors are renoprotective but did not
have a cardiovascular benefit.[74] [75] Some DPP-4 inhibitors require dose adjustment in renal
impairment.
Hypertension
• Hypertension is one of the greatest risk factors for the progression of CKD, regardless of aetiology.
Most patients with CKD will require at least two or three different types of antihypertensive agent to
achieve the optimal BP control.
• There is ongoing debate on the optimal BP target for patients with CKD. The 2014 Joint National
Committee 8 redefined the target BP goal for patients with CKD as <140/90 mmHg.[76] However,
the 2017 American College of Cardiology/American Heart Association guideline recommends
adults with hypertension and CKD should be treated to a BP goal of less than 130/80 mmHg.[77]
There may be benefit in strict BP control to reduce the relative risk of death, and delay the onset of
ESRD in some subgroups of patients with CKD (age ≥40 years, BMI ≥30 kg/m²).[78] [79] The 2021
Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends a target systolic
BP of less than 120 mmHg, if tolerated, in patients with CKD, with and without diabetes, and not
receiving dialysis.[58]
MANAGEMENT
• A combination of antihypertensive agents should be used to meet the target BP goal (except that
ACE inhibitors and angiotensin-II receptor antagonists should not be combined within the same
regimen).
• ACE inhibitors and angiotensin-II receptor antagonists have been shown in numerous clinical trials
to slow the progression of CKD and delay the need for renal replacement therapy in both diabetic
and non-diabetic CKD.[80] [81] [82] In one meta-analysis of patients with CKD, blockade of the
renin angiotensin system with either ACE inhibitors or angiotensin-II receptor antagonists reduced
the risk for kidney failure and cardiovascular events.[83] ACE inhibitors are also more likely to
reduce the risk of death in people with CKD.[83]
• Although previously thought that a complete blockade of the renin angiotensin system with
combination therapy of ACE inhibitors and angiotensin-II receptor antagonists or direct renin
inhibitors would delay progression in CKD, clinical trial results have failed to confirm any such
benefit and found an increased risk of hyperkalaemia and acute kidney injury.[84] Although not
recommended for CKD, combination therapy with ACE inhibitors and angiotensin-II receptor
antagonists is sometimes used in patients with nephrotic syndromes and glomerulonephritis to
reduce proteinuria.
• Other classes of antihypertensive agents (e.g., thiazide or thiazide-like diuretics, beta-blockers,
etc.) can be combined with ACE inhibitors or angiotensin-II receptor antagonists if target BP is not
achieved with these first-line agents, or if there are other specific clinical indications, such as beta-
blockers for angina pectoris.[58]
• Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist, reduces the
progression of kidney disease in patients with type 2 diabetes mellitus and known CKD.[85]
Finerenone is approved by the US Food and Drug Administration to reduce the risk of kidney
function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalisation for
heart failure in adults with CKD associated with type 2 diabetes.
Dyslipidaemia
• Dyslipidaemia is common in patients with CKD. Although specific treatment targets for cholesterol
and low-density lipoprotein have been recommended for CKD patients, this 'treat to target'
approach has not been well established in clinical trials.
• As such, the KDIGO guidelines recommend that CKD patients not on dialysis should start
treatment with a statin without the need for routine follow-up to check lipid values, or to change
treatment regimen based on set targets (i.e., a 'treat and forget' approach).[61] For patients
aged ≥50 years with CKD GFR category G3 or G4, ezetimibe can be combined with the statin
simvastatin.[62]
• Statin therapy has been shown to have cardioprotective effects in patients with CKD.[86] [87] [88]
[89] In those individuals not on dialysis therapy, the use of statins in a large meta-analysis resulted
in the reduction of all-cause mortality by 21% (relative risk [RR] 0.79, 95% CI 0.69 to 0.91) and
cardiovascular mortality by 23% (RR 0.77, 95% CI 0.69 to 0.87).[90] It was noted that there was no
difference in adverse effects for statin users as compared with those in the placebo arms. Despite
previous evidence that statins may be renoprotective via anti-inflammatory effects in the kidney, the
use of statins in these trials did reduce proteinuria but overall did not improve kidney function.
• Unfortunately, the beneficial effect of statin use in CKD has not been shown in the dialysis
population. In both single investigations and one meta-analysis, statin use in patients undergoing
dialysis did not improve all-cause mortality or cardiovascular-related deaths.[91]
GFR category G1 to G4 intolerant to first-line therapy

MANAGEMENT
If a patient is unable to tolerate either an ACE inhibitor or angiotensin-II receptor antagonist due to
adverse effects, then an alternative is warranted. Non-dihydropyridine calcium-channel blockers have
been demonstrated to have more proteinuric-lowering effects than other antihypertensive agents. Clinical
19
trials in both diabetic and non-diabetic CKD have demonstrated greater protein-lowering effects than other
classes of antihypertensive agents.[92]
GFR category G2
The directed therapy is to continue to modify cardiovascular risk factors, but also estimate the rate of loss
of kidney function to determine the eventual need for renal replacement therapy (i.e., dialysis, transplant).
GFR category G3a/G3b

Education can play a significant role in delaying progression of CKD, as well as helping the patient
understand his/her options if CKD progresses.[93] [94] [95] Most CKD-related complications occur during
this stage of transition (GFR category G3a/G3b). Identification of comorbidities such as anaemia and
secondary hyperparathyroidism is recommended, and treatment commenced if required.
Treatment of anaemia with the use of erythropoietin-stimulating agents is recommended for patients
with CKD after other causes of anaemia such as iron, vitamin B12, folate, or blood loss have been
excluded.[96] Patients with CKD frequently have iron deficiency, and iron replacement should be
considered as a goal of treatment.
Erythropoietin stimulating therapy may be initiated if the haemoglobin (Hb) falls to <100 g/L (<10 g/
dL) and the patient has symptoms and signs of anaemia. The target Hb for patients with CKD on
erythropoietin therapy has changed in the last several years but clinical expert opinion suggests that a
target of 100-110 g/L (10-11 g/dL) is appropriate, as normalisation of Hb has resulted in increased risk
for death and cardiovascular disease in this population.[97] [98] In the TREAT study of patients with
diabetes with CKD and anaemia, treatment with the erythropoietin-stimulating agent darbepoetin failed
to show a beneficial effect of active treatment on cardiovascular events, death, or ESRD as compared
with those receiving placebo (individuals would receive a rescue dose of medication if the haemoglobin
fell to <90g/L [<9 g/dL]).[99] Interestingly, as in other studies of anaemia treatment in CKD, the TREAT
investigators demonstrated that individuals in the active treatment arm had an increased risk of stroke
(RR 1.92, 95% CI 1.38 to 2.68).[100] In their opinion, the risks of treatment may outweigh the benefits,
and discussion between the patient and physician should ensue prior to treatment initiation.[96] [99] [101]
[102] All patients should have an assessment of iron stores if erythropoietin therapy is planned. The goal
ferritin for those not on haemodialysis is >100 nanograms/mL, while for those on haemodialysis it is <200
nanograms/mL. All patients should have a transferrin saturation >20%. Iron replacement can be given
orally or parenterally.[103]
For secondary hyperparathyroidism, calcium, phosphorus, and intact parathyroid hormone (PTH) levels
should be measured every 6 to 12 months. The calcium and phosphorus levels should be maintained
in the normal range with dietary restriction and/or phosphate-binding medications. The optimal PTH
level is currently not known. It is recommended to exclude concomitant 25-OH vitamin D deficiency and
prescribe 25, dihydroxyvitamin D if <75 nanomol/L (<30 nanograms/mL). For those with GFR category
G3 to G5 CKD not on dialysis, it is not routinely recommended to use active vitamin D analogues due to
the risk of hypercalcaemia and lack of improvement in clinically relevant outcomes.[104] Use of active
vitamin D analogue therapy in patients with CKD not requiring dialysis is indicated if hyperparathyroidism
MANAGEMENT
is progressive or severe.[104] [105] There is emerging evidence that the use of non-calcium-based
phosphate binders has a survival advantage over calcium-based phosphate binders in patients with
CKD.[104] [106] [Evidence B]
GFR category G4
Patients need to be educated about renal replacement therapy such as haemodialysis, peritoneal dialysis,
and kidney transplantation.[94] [107] Patients should be referred to surgery for dialysis access and/
or evaluated for kidney transplantation, based on patient preference for renal replacement modality
at this stage. All patients should undergo CKD education for modality choice.[94] Patient preference,
family support, underlying comorbid conditions, and proximity to a dialysis facility should be addressed
when choosing a modality or consideration for palliative care.[108] All patients who are proceeding with
haemodialysis should be educated about vein preservation with limiting venipuncture and intravenous
access in the access arm.[109] Kidney transplantation is indicated once the eGFR is <20 mL/minute and
the patient has been evaluated and undergone the required testing process by a transplant team.
Treatment of anaemia and secondary hyperparathyroidism should be continued. It is recommended to

check serum calcium and phosphate every 3 to 6 months, and intact PTH every 6 to 12 months.[104]
[Evidence C] Additionally, for those patients who develop metabolic acidosis, supplementation with oral
sodium bicarbonate has been shown to slow progression of CKD.[110] Oral sodium bicarbonate is well
tolerated in this group.
GFR category G5 and uraemia

Renal replacement therapy may be initiated once patients have G5 disease or signs of uraemia such as
weight loss, lack of appetite, nausea, vomiting, acidosis, hyperkalaemia, or fluid overload.[1] Treatment
of anaemia and secondary hyperparathyroidism should be continued. Those with G5 CKD on dialysis,
calcium, phosphorus, and intact PTH should be managed with phosphate binding agents, calcimimetics,
active vitamin D analogues, or a combination of these therapies, based on serial laboratory assessments
of calcium and phosphate every 1 to 3 months, and PTH every 3 to 6 months.[104] [Evidence C]
Calcimimetics (e.g., cinacalcet, etelcalcetide) negatively feedback on the parathyroid glands and do not
have the consequences of calcium augmentation.[111] Cinacalcet lowers PTH levels in patients with CKD
and secondary hyperparathyroidism both prior to and after the initiation of dialysis, but it is associated
with hypocalcaemia, and long-term benefits are not known.[112] [113]
There is no other medical therapy to keep patients alive once they have reached the need for dialysis,
other than kidney transplantation. Of note, patients aged over 80 years and those with significant
comorbidities, such as advanced congestive heart failure, may do poorly with dialysis and frequently are
not considered transplant candidates. For these patients, and for all patients approaching ESRD for that
matter, the treating nephrologist should have a discussion with the patient regarding end of life care and
palliative care as an additional option.[114]
For those who are considered transplant candidates, transplant confers a significant survival advantage
over maintenance dialysis therapy, predominantly due to a decrease in the risk of cardiovascular death.
All patients who are on dialysis therapy are potentially eligible for kidney transplantation. A transplant
centre including a nephrologist and transplant surgeon will determine the final eligibility and status of the
patient for kidney transplantation, after a complete medical history and evaluation.[115] [116]
Other measures
MANAGEMENT
Although data are more limited in the CKD population than in the general population, tobacco cessation
and weight loss are recommended. Severe protein restriction should not be recommended until late GFR
category G4 or G5 disease as a management strategy to delay the initiation of dialysis.[117] Severe
protein restriction may result in malnourishment and poorer outcomes.[118] Aspirin use has also been
21
beneficial for cardioprotection in those with CKD, although there is a higher risk for minor bleeding than in
the general population.
MANAGEMENT
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute ( summary )
GFR category G1 to G2 without
uraemia
1st ACE inhibitor or angiotensin-II receptor

antagonist
adjunct dapagliflozin
plus statin
adjunct additional antihypertensive therapy
adjunct glycaemic control
2nd non-dihydropyridine calcium-channel

blocker
plus statin

uraemia

antagonist
plus statin ± ezetimibe
adjunct education about renal replacement

therapy

blocker

MANAGEMENT

therapy
23
Acute ( summary )
with anaemia adjunct erythropoietin-stimulating agent
adjunct iron
with secondary plus dietary modification ± phosphate-binding

hyperparathyroidism drug
adjunct ergocalciferol
adjunct active vitamin D analogue
with metabolic acidosis adjunct oral sodium bicarbonate
GFR category G5 or with uraemia
1st dialysis
adjunct iron

adjunct calcimimetic ± active vitamin D analogue
2nd kidney transplant

MANAGEMENT
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute
uraemia

antagonist
Primary options
» lisinopril: 2.5 to 5 mg orally once daily

initially, adjust dose gradually according to
response, maximum dose depends on level
of impairment
OR
» ramipril: 1.25 mg orally once daily

of impairment
OR
» enalapril: 2.5 mg orally once daily initially,

adjust dose gradually according to response,
maximum dose depends on level of
impairment
OR
» perindopril: 2 mg orally once daily

of impairment
OR
» trandolapril: 0.5 mg orally once daily

of impairment
OR
» captopril: 12.5 to 25 mg orally two to three

MANAGEMENT
times daily initially, adjust dose gradually

according to response, maximum dose
depends on level of impairment
OR
25
Acute
» losartan: 50 mg orally once daily initially,
maximum 100 mg/day
OR
» irbesartan: 75 mg orally once daily initially,

maximum 300 mg/day
OR
» telmisartan: 20 mg orally once daily initially,

maximum 80 mg/day
» Several classes of agents have been

shown to slow CKD progression. Renin-
angiotensin system blockade and sodium-
glucose co-transporter 2 (SGLT2) inhibitors
(e.g., empagliflozin, canagliflozin, dapagliflozin)
can preserve kidney function by reducing intra-
glomerular pressure independently of blood
» The 2014 Joint National Committee 8

redefined the target BP goal for patients with
CKD as <140/90 mmHg, given the evidence
from clinical trials that this is associated with
the lowest risk of cardiovascular outcomes and
mortality.[76] However, the 2017 American
College of Cardiology/American Heart
Association guideline recommends adults with
hypertension and CKD should be treated to a BP
goal of less than 130/80 mmHg.[77] The Kidney
Disease: Improving Global Outcomes guideline
recommends a target systolic BP of less than
120 mmHg, if tolerated, in patients with CKD,
with and without diabetes, and not receiving
dialysis.[58]
» Clinical trials in both diabetic and non-diabetic

kidney disease have demonstrated that ACE
inhibitors or angiotensin-II receptor antagonists
are first-line agents for controlling BP and
reducing proteinuria in this population.
» Evidence for the use of ACE inhibitors

and angiotensin-II receptor antagonists in
combination for CKD is controversial. Although
current clinical evidence does not support the
MANAGEMENT
routine use of ACE inhibitors and angiotensin-

II receptor antagonists in combination for
the treatment of CKD, it is sometimes given
to patients with nephrotic syndromes and
glomerulonephritis to reduce proteinuria.[84]
Acute
» Both classes of drug may be associated
with hyperkalaemia and acute kidney injury,
more commonly in older people, those with
an estimated glomerular filtration rate (eGFR)
<30 mL/minute/1.73 m², and with use of longer-
acting agents. These complications are usually
reversible with medication discontinuation and
appropriate treatment.
» Doses should be low initially and adjusted

gradually according to clinical response.
Treatment recommended for SOME patients in
selected patient group
Primary options
» dapagliflozin: 10 mg orally once daily
» Dapagliflozin, a sodium-glucose co-transporter

2 (SGLT2) inhibitor, has been approved in
Europe and the US for the treatment of CKD
in adults at risk of progression (to reduce the
risk of sustained estimated glomerular filtration
rate [eGFR] decline, end-stage kidney disease,
cardiovascular death, and hospitalisation for
heart failure). It can be used in combination with
an ACE inhibitor or an angiotensin-II receptor
antagonist.
» Its use significantly reduces the relative

risk of worsening renal function in patients
with CKD stages 2 through 4. The DAPA-
CKD trial on dapagliflozin included adults with
CKD (GFR category G2-G4, eGFR 25-75 mL/
minute/1.73 m²), with or without type 2 diabetes,
and confirmed that the renoprotective effects
of dapaglifozin were independent of diabetes
status.[60]
» In patients with diabetes, who are not already

on an SGLT2 inhibitor with known cardiovascular
and renal benefits for glycaemic control,
dapagliflozin should be considered as a renal
preserving agent.
» Use of SGLT2 inhibitors is contraindicated in

patients with an eGFR of <30 mL/minute/1.73
m², including patients with end-stage renal
disease who are on dialysis.
plus statin
MANAGEMENT
Treatment recommended for ALL patients in

Primary options
» simvastatin: 20-40 mg orally once daily
27
Acute
OR
» pravastatin: 40 mg orally once daily
OR
» rosuvastatin: 5-10 mg orally once daily
OR
» atorvastatin: 10-20 mg orally once daily
» Statin therapy has been shown to have

cardioprotective effects in patients with CKD.[86]
[87] [88] [89] In those individuals not on dialysis
therapy, the use of statins in a large meta-
analysis resulted in the reduction of all-cause
mortality by 21% (relative risk [RR] 0.79, 95%
CI 0.69 to 0.91) and cardiovascular mortality by
23% (RR 0.77, 95% CI 0.69 to 0.87).[90]
» Total cholesterol and low-density lipoprotein

treatment targets for patients with CKD have not
been well established in clinical trials. As such,
the Kidney Disease: Improving Global Outcomes
guidelines recommend that CKD patients ≥50
years or those with a high risk of cardiovascular
mortality (not on dialysis) should be treated with
a statin without the need for routine follow-up to
check lipid values, or to change medication dose
regimens based on set targets (i.e., a 'treat and
forget' approach).[61]
» Statin therapy has been associated with

liver dysfunction and myopathy and should be
monitored in patients with CKD.
Primary options
» chlortalidone: 12.5 to 25 mg orally once

daily initially, adjust dose gradually according
to response, maximum 50 mg/day
-or-
» hydrochlorothiazide: 12.5 mg orally once
MANAGEMENT
OR
» atenolol: 25 mg orally once daily initially,

maximum 25-50 mg/day
Acute
OR
» metoprolol: 25 mg orally (extended-release)

once daily initially, adjust dose gradually
according to response, maximum 100 mg/day
OR
» nifedipine: 30-60 mg orally (extended-

release) once daily initially, adjust dose
gradually according to response, maximum
90 mg/day (120 mg/day for some brands)
OR
» amlodipine: 5 mg orally once daily initially,

maximum 10 mg/day
OR
» felodipine: 2.5 mg orally once daily initially,

maximum 20 mg/day
OR
» finerenone: 20 mg orally once daily
OR
» spironolactone: 12.5 mg orally once daily

response, maximum 200 mg/day given in 2-4
divided doses
Secondary options
» hydralazine: 10 mg orally three to four times

OR
» minoxidil: 5 mg orally once daily initially,

maximum 40 mg/day
OR
MANAGEMENT
» clonidine: 0.1 mg orally (immediate-release)

twice daily initially, adjust dose gradually
according to response, maximum 0.6 mg/day
29
Acute
» Other classes of antihypertensive agents (e.g.,
thiazide, or thiazide-like diuretics, beta-blockers,
etc.) should be added when the target blood
pressure is not achieved with the use of an ACE
inhibitor or angiotensin-II receptor antagonist,
or if there are other specific clinical indications,
such as beta-blockers for angina pectoris.[58]
» Finerenone, a non-steroidal selective

mineralocorticoid receptor antagonist, reduces
the progression of kidney disease in patients
with type 2 diabetes mellitus and known
CKD.[85] Finerenone is approved by the US
Food and Drug Administration to reduce the
risk of kidney function decline, kidney failure,
cardiovascular death, non-fatal heart attacks,
and hospitalisation for heart failure in adults with
CKD associated with type 2 diabetes.
» In patients with diabetes, glycaemic goals
should be individualised. For many patients,
the goal of HbA1c <7% is appropriate.
However, HbA1c 7.0% to 7.9% may be more
appropriate in some patients, such as those with
advanced age, limited life expectancy, known
cardiovascular disease, high risk of severe
hypoglycaemia, or difficulty achieving lower
HbA1c goals despite the use of multiple anti-
hyperglycaemic medications and insulin.[20] [64]
In patients with diabetes and CKD, there is a risk
for hypoglycaemia because of impaired kidney
clearance of medications, such as insulin (two-
thirds of insulin is degraded by the kidney) or
sulfonylureas, and because of impaired kidney
gluconeogenesis.
» Patients with type 1 diabetes require treatment

with insulin, regardless of whether they are on
dialysis or not.
» Some specific anti-hyperglycaemic

medications used by patients with type 2
diabetes significantly reduce all-cause or
cardiovascular mortality, or major cardiovascular
events or renal complications in some
patient subgroups, and may be considered
independently of HbA1c targets.[65] [57] [66]
[67]
MANAGEMENT
» There is evidence that the use of sodium-

prevents major kidney outcomes (e.g., dialysis,
transplantation, or death due to kidney
Acute
disease) in people with type 2 diabetes.[68]
[60] SGLT2 inhibitors, in addition to reducing
hyperglycaemia, have renal benefits through
independent effects on renal tubular glucose
reabsorption, weight, blood pressure, intra-
glomerular pressure, albuminuria, and slowed
glomerular filtration rate (GFR) loss.[69] [70]
The use of SGLT2 inhibitors is not generally
recommended in patients with an estimated
GFR (eGFR) of <45 mL/minute/1.73 m² (<60
mL/minute/1.73 m² for ertugliflozin); however,
the CREDENCE trial included patients with
an eGFR 30 to 90 mL/minute/1.73 m² and
demonstrated a decreased risk of kidney failure
and cardiovascular events.[71] Use of SGLT2
inhibitors is contraindicated in patients with
an eGFR of <30 mL/minute/1.73 m², including
patients with end-stage renal disease who are
on dialysis. If additional glycaemic control is
required for patients already on dapagliflozin as
a renal preserving drug, a drug from one of the
other groups should be selected.
» As a class of drugs, glucagon-like peptide-1

(GLP-1) agonists have beneficial effects on
cardiovascular, mortality, and kidney outcomes
in patients with type 2 diabetes.[72] Experience
with GLP-1 agonists in patients with renal
dysfunction is limited; therefore, these agents
should be used with caution.[73] Liraglutide,
albiglutide, dulaglutide, and semaglutide are not
renally excreted and are the preferred agents in
this class.
» Studies report that dipeptidyl peptidase-4

(DPP-4) inhibitors are renoprotective, but did not
have a cardiovascular benefit.[74] [75] Some
DPP-4 inhibitors require dose adjustment in
renal impairment.
blocker
Primary options
» diltiazem: 120 mg orally (extended-release)

OR
» verapamil: 120 mg orally (extended-

MANAGEMENT

360 mg/day
31
Acute
» ACE inhibitors and angiotensin-II receptor
antagonists are the superior treatment for
patients with CKD.
» If these medicines need to be discontinued

due to adverse effects such as cough, angio-
oedema, haemodynamic decline in renal
function, and/or hyperkalaemia, then non-
dihydropyridine calcium-channel blockers have
been demonstrated to have more proteinuric-
lowering effects than other antihypertensive
agents.[119]
Primary options

heart failure).

status.[60]

preserving agent.

plus statin
MANAGEMENT

Primary options
Acute
OR
OR
OR

23% (RR 0.77, 95% CI 0.69 to 0.87).[90]

treatment targets for patients with CKD have not
been well established in clinical trials. As such,
the Kidney Disease: Improving Global Outcomes
guidelines recommend that CKD patients not on
dialysis should be treated with a statin without
the need for routine follow-up to check lipid
values, or to change medication dose regimens
based on set targets (i.e., a 'treat and forget'
approach).[61]

Primary options

OR

MANAGEMENT
OR
33
Acute
OR

OR

OR

maximum 10 mg/day
OR

maximum 20 mg/day
OR
OR

divided doses
OR
» aliskiren: 150 mg orally once daily initially,

maximum 300 mg/day
Secondary options

MANAGEMENT

OR
Acute
maximum 40 mg/day
OR


pressure is not achieved with the use of a non-
dihydropyridine calcium-channel blocker, or if
there are other specific clinical indications, such
as beta-blockers for angina pectoris.[58]

gluconeogenesis.

MANAGEMENT
dialysis or not.

medications used by patients significantly reduce
all-cause or cardiovascular mortality, or major
cardiovascular events or renal complications
35
Acute
in some patient subgroups, and some may be
considered independently of HbA1c targets.[65]
[57] [66] [67]


this class.

renal impairment.
uraemia
MANAGEMENT

antagonist
Primary options
» lisinopril: 2.5 to 5 mg orally once daily

Acute
of impairment
OR
» ramipril: 1.25 mg orally once daily

of impairment
OR
» enalapril: 2.5 mg orally once daily initially,

maximum dose depends on level of
impairment
OR
» perindopril: 2 mg orally once daily

of impairment
OR
» trandolapril: 0.5 mg orally once daily

of impairment
OR
» captopril: 12.5 to 25 mg orally two to three

times daily initially, adjust dose gradually
according to response, maximum dose
depends on level of impairment
OR
» losartan: 50 mg orally once daily initially,

maximum 100 mg/day
OR
» irbesartan: 75 mg orally once daily initially,

maximum 300 mg/day
MANAGEMENT
OR
37
Acute
» telmisartan: 20 mg orally once daily initially,
maximum 80 mg/day
» Several classes of agents have been

shown to slow CKD progression. Renin-
angiotensin system blockade and sodium-
can preserve kidney function by reducing intra-
glomerular pressure independently of blood
» The Joint National Committee 8 redefined

the target BP goal for patients with CKD as
<140/90 mmHg, given the evidence from clinical
trials that this is associated with the lowest risk
of cardiovascular outcomes and mortality.[76]
However, the 2017 American College of
Cardiology/American Heart Association
guideline recommends adults with hypertension
and CKD should be treated to a BP goal of
less than 130/80 mmHg.[77] The Kidney
Disease: Improving Global Outcomes guideline
recommend a target systolic BP of less than
120 mmHg, if tolerated, in patients with CKD,
with and without diabetes, and not receiving
dialysis.[58]
» Clinical trials in both diabetic and non-diabetic

kidney disease have demonstrated that ACE
inhibitors or angiotensin-II receptor antagonists
are first-line agents for controlling BP and
reducing proteinuria in this population.
» Evidence for the use of ACE inhibitors

and angiotensin-II receptor antagonists in
combination for CKD is controversial. Although
current clinical evidence does not support the
routine use of ACE inhibitors and angiotensin-
II receptor antagonists in combination for
the treatment of CKD, it is sometimes given
to patients with nephrotic syndromes and
glomerulonephritis to reduce proteinuria.[84]
» Both classes of drug may be associated

with hyperkalaemia and acute renal failure,
more commonly in older people, those with
an estimated GFR <30 mL/minute/1.73 m²,
and with use of longer-acting agents. These
complications are usually reversible with
medication discontinuation and appropriate
MANAGEMENT
treatment.
Acute
Primary options

heart failure). It can be used in combination with
an ACE inhibitor or an angiotensin-II receptor
antagonist.

status.[60]

preserving agent.

Primary options
OR
OR

MANAGEMENT
OR
OR
39
Acute
» ezetimibe/simvastatin: 10 mg (ezetimibe)/20
mg (simvastatin) orally once daily

23% (RR 0.77, 95% CI 0.69 to 0.87).[90]

treatment targets for patients with CKD have
not been well established in clinical trials.
As such, the Kidney Disease: Improving
Global Outcomes guidelines recommend that
GFR category G3 or G4 CKD patients not on
dialysis should be treated with a statin without
the need for routine follow-up to check lipid
values, or to change medication dose regimens
based on set targets (i.e., a 'treat and forget'
approach).[61] For patients aged ≥50 years
with CKD category G3 or G4, ezetimibe can be
added to simvastatin.[62]

Primary options

OR

OR

MANAGEMENT
OR
Acute
OR

OR

maximum 10 mg/day
OR

maximum 20 mg/day
OR
OR

divided doses
Secondary options

OR

maximum 40 mg/day
OR

MANAGEMENT


41
Acute
pressure is not achieved with the use of an ACE
inhibitor or angiotensin-II receptor antagonist,
or if there are other specific clinical indications,
such as beta-blockers for angina pectoris.[58]

gluconeogenesis.

dialysis or not.

medications significantly reduce all-cause or
[67]

MANAGEMENT

Acute

this class.

renal impairment.
therapy
» Patients need to be educated about renal
replacement therapy such as haemodialysis,
peritoneal dialysis, and kidney transplantation.
Patient preference, family support, underlying
comorbid conditions, and proximity to a dialysis
facility should be addressed when choosing
a modality or consideration for palliative care.
All patients should undergo CKD education for
modality choice.[94]
» Patients should be referred to surgery for

MANAGEMENT
dialysis access and/or evaluated for kidney

transplantation, based on patient preference
for renal replacement modality at glomerular
filtration rate (GFR) category G4.
43
Acute
» All patients who are proceeding with
haemodialysis should be educated about vein
preservation with limiting venipuncture and
intravenous access in the access arm.[109]
» Kidney transplantation is indicated once the

estimated GFR is <20 mL/minute and the patient
has been evaluated and undergone the required
testing process by a transplant team.
blocker
Primary options
» diltiazem: 120 mg orally (extended-release)

OR
» verapamil: 120 mg orally (extended-

360 mg/day
» ACE inhibitors and angiotensin-II receptor

antagonists are the superior treatment for
patients with CKD.
» If these medicines need to be discontinued

due to adverse effects such as cough, angio-
oedema, haemodynamic decline in renal
function, and/or hyperkalaemia, then non-
dihydropyridine calcium-channel blockers have
been demonstrated to have more proteinuric-
lowering effects than other antihypertensive
agents.[119]
Primary options

MANAGEMENT

heart failure).

Acute
status.[60]

preserving agent.

Primary options
OR
OR
OR
OR
» ezetimibe/simvastatin: 10 mg (ezetimibe)/20
mg (simvastatin) orally once daily

23% (RR 0.77, 95% CI 0.69 to 0.87).[90]
MANAGEMENT

treatment targets for patients with CKD have
not been well established in clinical trials. As
such, the Kidney Disease: Improving Global
Outcomes guidelines recommend that GFR
45
Acute
category G3 or G4 CKD patients not on dialysis
should be treated with a statin without the need
for routine follow-up to check lipid values, or to
change medication dose regimens based on set
targets (i.e., a 'treat and forget' approach).[61]
For patients aged ≥50 years with CKD GFR
category G3 or G4, ezetimibe can be added to
simvastatin.[62]

Primary options

OR

OR

OR

OR

OR
MANAGEMENT

maximum 10 mg/day
OR
Acute
maximum 20 mg/day
OR
OR

divided doses
OR
» aliskiren: 150 mg orally once daily initially,

maximum 300 mg/day
Secondary options

OR

maximum 40 mg/day
OR

» Other classes of antihypertensive agent (e.g.,

pressure is not achieved with the use of a non-
dihydropyridine calcium-channel blocker, or if
there are other specific clinical indications, such
as beta-blockers for angina pectoris.[58]

MANAGEMENT

CKD.[85] Fineinerenone is approved by the US
47
Acute
gluconeogenesis.

dialysis or not.

medications significantly reduce all-cause or
[67]

MANAGEMENT

Acute

this class.

renal impairment.
therapy
» Patients need to be educated about renal
replacement therapy such as haemodialysis,
peritoneal dialysis, and kidney transplantation.
Patient preference, family support, underlying
comorbid conditions, and proximity to a dialysis
facility should be addressed when choosing
a modality or consideration for palliative care.
All patients should undergo CKD education for
» Patients should be referred to surgery for

dialysis access and/or evaluated for kidney
transplantation, based on patient preference for
renal replacement modality at GFR category G4.
» All patients who are proceeding with

haemodialysis should be educated about vein
preservation with limiting venipuncture and
intravenous access in the access arm.[109]
» Kidney transplantation is indicated once the

estimated GFR is <20 mL/minute and the patient
has been evaluated and undergone the required
testing process by a transplant team.
MANAGEMENT

Primary options
49
Acute
» epoetin alfa: consult specialist for guidance
on dose
OR
» darbepoetin alfa: consult specialist for

guidance on dose
» When GFR category G3a/G3b has been

reached, identification of comorbidities such
as anaemia is recommended and treatment
begun if required. Treatment of anaemia with
the use of erythropoietin-stimulating agents is
recommended for patients with CKD after other
causes of anaemia such as iron, vitamin B12,
folate, or blood loss have been excluded.[96]
Due to the possibility of an increased risk of
stroke in those on erythropoietin-stimulating
agents, discussion between the patient and
physician should ensue prior to treatment
initiation.[96] [99] [101] [102]
» Erythropoietin-stimulating agents are initiated

once the haemoglobin (Hb) falls to <10 g/dL and
the patient has signs and symptoms of anaemia.
» The target Hb for patients with CKD on

erythropoietin therapy is 10 to 11 g/dL, as
normalisation of Hb has resulted in increased
risk for death and cardiovascular disease in this
population.[97] [98]
adjunct iron
Primary options
» ferrous sulfate: 60 mg orally once to three

times daily
Dose refers to elemental iron.
OR
» ferrous gluconate: 60 mg orally once to

three times daily
Secondary options
» sodium ferric gluconate complex: consult

specialist for guidance on dose
MANAGEMENT
OR
» iron sucrose: consult specialist for guidance

on dose
Acute
OR
» ferumoxytol: consult specialist for guidance

on dose
OR
» ferric carboxymaltose: consult specialist for

guidance on dose
» All patients should have an assessment of

iron stores if erythropoietin therapy is planned.
The goal ferritin for those not on haemodialysis
is >100 nanograms/mL, while for those on
haemodialysis is >200 nanograms/mL. All
patients should have a transferrin saturation
>20%. Iron replacement can be given orally or
parenterally.[103] [120]
Primary options
» sevelamer: 800-1600 mg orally three times

daily, titrate according to serum phosphate
level
OR
» calcium acetate: 1334 mg orally with each

meal, titrate according to serum phosphate
level
OR
» calcium carbonate: 1-2 g/day orally given in

3-4 divided doses
OR
» lanthanum: 500-1000 mg orally three times

daily, titrate according to serum phosphate
level
OR
» sucroferric oxyhydroxide: 500 mg orally

MANAGEMENT
three times daily initially, titrate according to

serum phosphate level, maximum 3000 mg/
day
OR
51
Acute
» colestilan: 2-3 g orally three times daily
initially, titrate according to serum phosphate
level, maximum 15 g/day
» When GFR category G3a/G3b has been

reached, identification of comorbidities such as
secondary hyperparathyroidism is recommended
and treatment begun if required. The calcium
and phosphorus levels should be maintained in
the normal range with dietary restriction and/or
phosphate-binding medications.
» Phosphate binders should be initiated to

normalise phosphorus levels if patients are
unable to sufficiently restrict phosphorus
in the diet.[104] Calcium-based phosphate
binders should be restricted if there is
associated hypercalcaemia, arterial calcification,
suppressed parathyroid hormone (PTH), or
adynamic bone disease.[104]
» Calcium, phosphorus, and PTH testing

should be performed every 6 to 12 months for
patients with GFR category G3a/G3b CKD and
secondary hyperparathyroidism. For patients
with GFR category G4 CKD and secondary
hyperparathyroidism, calcium and phosphate
should be checked every 3 to 6 months, and
PTH every 6 to 12 months.[104] [Evidence C]
» There is limited evidence that dietary

restriction in calcium and phosphorus affects
renal osteodystrophy.[121]
» There is emerging evidence that the use of

non-calcium-based phosphate binders has
a survival advantage over calcium-based
phosphate binders in patients with CKD.[104]
[106] [Evidence B]
Primary options
» ergocalciferol: dose depends on serum

25-OH vitamin D level; consult specialist for
guidance on dose
» It is recommended to exclude concomitant

25-OH vitamin D deficiency and prescribe 25,
dihydroxyvitamin D if <30 nanograms/dL.
MANAGEMENT
adjunct active vitamin D analogue

Acute
Primary options
» calcitriol: consult specialist for guidance on

dose
OR
» paricalcitol: consult specialist for guidance

on dose
OR
» doxercalciferol: consult specialist for

guidance on dose
» It is not routinely recommended to use

active vitamin D analogues for CKD not
requiring dialysis unless hyperparathyroidism is
progressive or severe.[104]
» The optimal parathyroid hormone level is

currently not known.
with metabolic acidosis adjunct oral sodium bicarbonate
Primary options
» sodium bicarbonate: consult specialist for

guidance on dose
» For patients who develop metabolic acidosis,

supplementation with oral sodium bicarbonate
has been shown to slow progression of
CKD.[110] Oral sodium bicarbonate is well
tolerated in this group.
GFR category G5 or with uraemia
GFR category G5 or with 1st dialysis

uraemia
» Renal replacement therapy is initiated once
patients have GFR category G5 disease
and/or signs of uraemia such as weight loss,
lack of appetite, nausea, vomiting, acidosis,
hyperkalaemia, or fluid overload.[1]
» Renal replacement therapy in the form of

dialysis is designed to remove toxic waste
products from the blood, such as urea, and
normalise potassium and serum bicarbonate
MANAGEMENT
levels, as well as to remove fluid that will

accumulate once the kidneys have failed.
» All patients should undergo CKD education for

53
Acute
» Peritoneal dialysis is performed at home
and is available to all patients. A peritoneal
dialysis catheter is inserted into the abdomen
and dialysis fluid is instilled in order to allow for
toxic waste products and fluid to be removed and
drained from the body on a daily basis.
» Continuous cycling peritoneal dialysis is done

with a machine at night on a daily basis.
» Continuous ambulatory peritoneal dialysis

is done on a daily basis. Patients manually
exchange the peritoneal fluid.
» Haemodialysis is usually prescribed

in a treatment centre 3 times a week for
approximately 4 hours each session.
Haemodialysis can also be carried out at
home, usually 4 to 5 days a week, 3 to 4 hours
a day. The patient's blood is removed from
the body through an arteriovenous fistula,
an arteriovenous graft, or a dialysis catheter,
and then returned after traversing a dialysis
membrane and dialysis solution. Other dialysis
options include short daily dialysis and nocturnal
dialysis, which are available at some treatment
centres.
Primary options
» epoetin alfa: consult specialist for guidance

on dose
OR
» darbepoetin alfa: consult specialist for

guidance on dose
» Treatment of anaemia with the use

of erythropoietin-stimulating agents is
recommended for patients with CKD after other
causes of anaemia such as iron, vitamin B12,
folate, or blood loss have been excluded.[96]
Due to the possibility of an increased risk of
stroke in those on erythropoietin-stimulating
agents, discussion between the patient and
physician should ensue prior to treatment
initiation.[96] [99] [101] [102]
MANAGEMENT
» Erythropoietin-stimulating agents are initiated

once the haemoglobin (Hb) falls to <10 g/dL and
the patient has signs and symptoms of anaemia.
Acute
» The target Hb for patients with CKD on
erythropoietin therapy is 10 to 11 g/dL, as
normalisation of Hb has resulted in increased
risk for death and cardiovascular disease in this
population.[97] [98]
adjunct iron
Primary options
» ferrous sulfate: 60 mg orally once to three

times daily
OR
» ferrous gluconate: 60 mg orally once to

three times daily
OR
» sodium ferric gluconate complex: consult

OR
» iron sucrose: consult specialist for guidance

on dose
OR
» ferumoxytol: consult specialist for guidance

on dose
OR
» ferric carboxymaltose: consult specialist for

guidance on dose
OR
» ferric pyrophosphate citrate: consult

» All patients should have an assessment of

iron stores if erythropoietin therapy is planned.
The goal ferritin for those not on haemodialysis
MANAGEMENT
is >100 nanograms/mL, while for those on

haemodialysis it is >200 nanograms/mL. All
patients should have a transferrin saturation
>20%. Iron replacement can be given orally or
parenterally.[103] [120] Oral iron will be sufficient
to maintain and attain the Hb within targets
55
Acute
in erythropoietin-stimulating agent-treated
CKD patients on peritoneal dialysis; however,
most patients on haemodialysis will require
intravenous iron.[122]
Primary options
» sevelamer: 800-1600 mg orally three times

daily initially, titrate according to serum
phosphate level
OR
» calcium acetate: 1334 mg orally with each

meal initially, titrate according to serum
phosphate level
OR
» calcium carbonate: 1-2 g/day orally given in

3-4 divided doses
OR
» lanthanum: 500-1000 mg orally three

times daily initially, titrate according to serum
phosphate level
OR
» sucroferric oxyhydroxide: 500 mg orally

three times daily initially, titrate according to
serum phosphate level, maximum 3000 mg/
day
» For patients with GFR category G5 CKD

on dialysis, calcium, phosphorus, and intact
parathyroid hormone (PTH) levels should be
managed with phosphate binding agents,
calcimimetics, active vitamin D analogues, or a
combination of these based on serial laboratory
assessments.
» Phosphate binders such as calcium,

lanthanum, and sevelamer should be
initiated to normalise phosphorus levels if
MANAGEMENT
patients are unable to sufficiently restrict

phosphorus in the diet.[104] Calcium-based
phosphate binders should be restricted if
there is associated hypercalcaemia, arterial
Acute
calcification, suppressed PTH, or adynamic bone
disease.[104]
» Increasing dialytic phosphate removal

may be required in cases of persistent
hyperphosphataemia.
» Calcium and phosphorus testing every 1

to 3 months and PTH testing every 3 to 6
months should be performed for patients
with GFR category G5 CKD and secondary
hyperparathyroidism.[104] [Evidence C]
adjunct calcimimetic ± active vitamin D analogue
Primary options
» cinacalcet: 30 mg orally once daily initially,

increase dose according to serum PTH level,
maximum 180 mg/day
--AND/OR--
dose
-or-
on dose
-or-
guidance on dose
Secondary options
» etelcalcetide: adults: 5 mg intravenously

three times weekly at the end of
haemodialysis treatment, adjust dose
according to PTH level and corrected serum
calcium response, maintenance dose ranges
from 2.5 to 15 mg three times weekly
--AND/OR--
dose
-or-
on dose
-or-
guidance on dose
» For those requiring parathyroid hormone

MANAGEMENT
(PTH)-lowering therapy, calcimimetics (e.g.,

cinacalcet, etelcalcetide), active vitamin
D analogues (e.g., calcitriol, paricalcitol,
doxercalciferol), or a combination of a
calcimimetic with an active vitamin D analogue
should be given.[104]
57
Acute
» Etelcalcetide is a second-generation, type II
calcimimetic that may be used when treatment
with a calcimimetic is indicated but cinacalcet
is not a suitable option. It is given intravenously
(rather than orally like cinacalcet) and has a
longer half-life than cinacalcet.
Primary options
» ergocalciferol: dose depends on serum

25-OH vitamin D level; consult specialist for
guidance on dose
» It is recommended to exclude concomitant

25-OH vitamin D deficiency and prescribe 25,
dihydroxyvitamin D if <30 nanograms/dL.
2nd kidney transplant
» Kidney transplant confers a significant survival

advantage over maintenance dialysis therapy,
predominantly due to a decrease in the risk
of cardiovascular death. All patients who are
on dialysis therapy are potentially eligible for
kidney transplantation. A transplant centre
including a nephrologist and transplant surgeon
will determine the final eligibility and status
of the patient for kidney transplantation, after
a complete medical history and evaluation.
Kidneys may be transplanted from deceased or
living donors.
MANAGEMENT
Emerging
Roxadustat
Roxadustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates
erythropoiesis and regulates iron metabolism. It shows promise as an alternative to epoetin alfa as a therapy
for anaemia in patients with CKD. It is currently in phase 3 clinical trials.[123] [124] One meta-analysis of
existing phase 2 and phase 3 trials concluded that haemoglobin levels increased in patients with CKD who
were not on dialysis and haemoglobin levels were maintained in those patients requiring dialysis.[125] The
European Medicines Agency has approved the use of roxadustat for the treatment of adults with symptomatic
anaemia associated with CKD. The US Food and Drug Administration has requested further trials on the
safety of roxadustat in both non-dialysis-dependent and dialysis-dependent patient populations.
Daprodustat
Daprodustat is an oral inhibitor of HIF prolyl-hydroxylase. In phase 3 trials of patients with CKD (not
undergoing dialysis and undergoing dialysis) and anaemia, it was shown to be non-inferior to erythropoiesis-
stimulating agents for change in the haemoglobin level from baseline and major cardiovascular adverse
events.[126] [127] Daprodustat is currently approved for use in Japan.
Veverimer
Veverimer is a non-absorbed polymer which selectively binds and removes hydrochloric acid from the
gastrointestinal lumen and is being investigated for the treatment of metabolic acidosis in patients with CKD.
It has been shown to significantly increase serum bicarbonate concentration, with minimal adverse effects.
The US Food and Drug Administration is currently reviewing an application for approval.[128] [129]
Primary prevention
The evidence for the prevention of CKD is lacking as compared with large-scale randomised trials for
cardiovascular disease. Most trials have focused on modifiable diseases and risk factors that have been
associated with CKD, namely diabetes and hypertension. Clinical evidence supports the recommendation
for a goal HbA1c <7%, blood pressure target of <140/90 mmHg, tobacco cessation, and ideal body
weight with BMI <27 to prevent the development of CKD.[29] [26] [42] Due to the lack of widespread
screening guidelines with serum creatinine or urinary albumin, often patients are diagnosed after CKD has
developed.[43]
Secondary prevention
Prevention of further kidney function loss is the primary goal in conservative management of people with
CKD.[59] Kidney-preserving care includes non-pharmacological (e.g., dietary and lifestyle adjustments) and
pharmacological strategies.[59] Underlying risk factors associated with disease states should be treated,
including optimisation of glycaemic control in diabetes and achievement of the goal blood pressure of
<140/90 mmHg with ACE inhibitors or angiotensin-II receptor antagonists. Consideration can be given to
a lower blood pressure goal in those with proteinuria of >500 mg per 24 hours.[76] [77] [83] Although data
are limited in the CKD population as compared with the general population, tobacco cessation, weight
loss, salt restriction, and optimal lipid management with statin therapy are indicated. Protein restriction is
recommended in late-stage (GFR category G4 or G5) disease, as a management strategy to delay the
initiation of dialysis; however, severe protein restriction may result in malnourishment and impact on quality
of life.[117] Aspirin use has also been beneficial for cardioprotection in those with CKD, although there is a
MANAGEMENT
higher risk for minor bleeding than in the general population.
59
Patient discussions
Patients with CKD need to take an active role in managing their disease and monitoring their progression
to more advanced stages such as glomerular filtration rate (GFR) category G4 to G5. Dietary therapy
such as restriction of potassium, phosphorus and salt, protein, and fluids is typically advocated for GFR
category G3 to G5. Lifestyle changes that would include medical compliance, optimisation of glycaemic
control, and blood pressure control are the leading factors that delay progression of CKD and the need
for renal replacement therapy. As patients enter GFR category G4 CKD, it is recommended that they
attend educational classes at a CKD clinic where different dialysis modalities such as haemodialysis
and peritoneal dialysis are discussed, to determine their option of choice. In addition, patients may be
evaluated for kidney transplantation and referred to a transplant centre at this time. Once a patient has
been educated and the dialysis modality has been chosen, referral for surgery may be done for dialysis
access placement.
MANAGEMENT
Chronic kidney disease Follow up
Monitoring
Monitoring
FOLLOW UP
Patients with risk factors for CKD, such as diabetes, hypertension, or a family member with CKD,
should be evaluated annually with serum creatinine and mathematical formulation for estimation of the
glomerular filtration rate in addition to urinalysis for haematuria and/or proteinuria.
For those with established CKD, the rate of progression of CKD should be serially assessed starting in
glomerular filtration rate (GFR) category G3a/G3b disease. Patients should be screened for anaemia
and bone mineral disorders at least every 6 to 12 months, with a haemoglobin, calcium, phosphorus,
and intact parathyroid hormone (PTH). For those in GFR category G4 disease, haemoglobin, calcium,
phosphorus should be monitored every 3 to 6 months and intact PTH every 6 to 12 months. For patients
in GFR category G5 CKD, anaemia should be evaluated with a monthly haemoglobin, and bone mineral
disease with a calcium and phosphorus every 1 to 3 months and an intact PTH every 3 to 6 months.
Lipids should be checked annually for all patients with CKD.
61
Complications
Complications Timeframe Likelihood

FOLLOW UP
anaemia long term high
Anaemia of chronic kidney disease is due to a deficiency of erythropoietin as the glomerular filtration rate
(GFR) declines.
Anaemia is typically identified in GFR category G3a/G3b CKD. Patients should be screened with a full
blood count at least every 6 to 12 months, and an erythropoietin-stimulating agent may be considered
once the haemoglobin (Hb) falls to <100 g/L (<10 g/dL) and there are symptoms of anaemia. The target
Hb is 100 to 110 g/L (10 to 11 g/dL).[96] [99] [130]
If the patient is iron-deficient, oral or intravenous supplementation may also be prescribed.[103]
Patients with CKD on erythropoietin-stimulating agents for the treatment of anaemia have a higher risk of
death and cardiovascular complications if the Hb is normalised >130 g/L (>13 g/dL).[98] [97] [131] [132]
[133]
renal osteodystrophy long term high
May be caused by an elevation in parathyroid hormone (PTH) as a result of phosphorus retention and
hypocalcaemia from 1,25 vitamin D deficiency as the glomerular filtration rate (GFR) declines. Severe
hyperparathyroidism and hyperphosphataemia are risk factors for death, cardiovascular disease, and
vascular calcification in patients with CKD.[104] [Evidence C]
Patients with GFR category G3 to G5 CKD should be routinely monitored for hyperparathyroidism
and treatments based on serial assessments of phosphorus, calcium, and PTH levels, considered
together.[104]
25-dihydroxyvitamin D should be monitored and treated if the level is <30 nanograms/L.[134] [135]
cardiovascular disease long term high
CKD is a risk factor for cardiovascular disease independent of comorbidities such as diabetes,
hypertension, and dyslipidaemia. Cardiovascular disease is the leading cause of death for these
patients, and the overwhelming majority of patients with CKD will die prior to reaching the need for renal
replacement therapy.
The goal in treatment of cardiovascular disease in patients with CKD is early recognition and risk factor
modification, including lipid therapy, optimisation of blood pressure and glycaemic control, tobacco
cessation, and aspirin use.[137] [138]
protein malnutrition variable medium
As the glomerular filtration rate falls, patients develop anorexia, nausea, vomiting, and lack of protein
intake. Previously, patients with advanced CKD were placed on very-low- to low-protein diets to reduce
the risk for end-stage kidney disease, but this recommendation has limitations due to its worsening of
malnutrition. It is recommended for patients with CKD stages 3 to 5 who are metabolically stable to have
0.6 g/kg body weight protein intake daily and those with diabetes (not on dialysis) to have 0.6 to 0.8 g/kg
body weight protein intake daily.[136] In patients on dialysis, a dietary protein intake of 1.0 to 1.2 g/kg body
weight daily is recommended to maintain a stable nutritional status.[136]
Complications Timeframe Likelihood

metabolic acidosis variable medium
FOLLOW UP
Metabolic acidosis is common in patients with CKD, due to the inability of the kidney to excrete acid
once the estimated glomerular filtration rate is <50 mL/minute. The anion gap is typically normal, but
may be increased in uraemia with retention of phosphate anions. Rarely does the serum bicarbonate
level fall below 12 mmol/L (12 mEq/L). Metabolic acidosis may worsen renal osteodystrophy and cause
malnutrition, hypercatabolism, and growth retardation.
Treatment involves the administration of sodium bicarbonate 0.5 to 1.0 mmol/kg/day (0.5 to 1.0 mEq/kg/
day) for a target serum bicarbonate level >20 mmol/L (>20 mEq/L). Sodium citrate as a bicarbonate source
is generally avoided in patients with CKD, as it increases the absorption of aluminium and may contribute
to bone disease and dementia.[139] [140]
hyperkalaemia variable medium
Hyperkalaemia is common in patients with CKD, due to the kidney's inability to excrete potassium from
the diet as the estimated glomerular filtration rate declines. Hyperkalaemia is more common in patients
with oliguria, resistant or deficient aldosterone state, or co-existing metabolic acidosis. Most patients with
hyperkalaemia are asymptomatic, but some may present with muscle weakness.
The hallmark for the severity of hyperkalaemia is identification of cardiac disturbances on an ECG
with peaked T waves, prolongation of the conduction system, sine wave, or asystole. Hyperkalaemia
associated with cardiac conduction disturbances is a medical emergency and is treated with intravenous
calcium; medicines to shift potassium into the cells, such as insulin and dextrose; beta-agonists and the
focused removal of potassium from the body with loop diuretics, if kidney function is intact; oral potassium
binders (e.g., sodium polystyrene sulfonate, patiromer, sodium zirconium cyclosilicate); and, in severe
cases, haemodialysis.
pulmonary oedema variable medium
Fluid overload occurs in patients with CKD, especially those with concomitant congestive heart failure.
Treatment of fluid overload with loop diuretics is often used to prevent episodes of pulmonary oedema and
manage peripheral oedema. In some instances, a combination diuretic regimen (e.g., a loop and a thiazide
diuretic) provides a more effective diuresis in patients. Failure to maintain fluid balance in those with
advanced glomerular filtration rate category G4 and G5 CKD is an indication to start renal replacement
therapy.
Prognosis
CKD is mostly progressive and leads to end-stage renal disease (ESRD) and the need for renal replacement
therapy (i.e., dialysis, transplant). Though it cannot be cured, it can be controlled and managed to a large
extent. CKD is a strong cardiovascular risk factor, and the majority of patients with CKD will die prior to
reaching ESRD. As kidney function declines, complications such as anaemia and hyperparathyroidism
develop that may contribute to worsening cardiovascular disease and renal osteodystrophy, respectively.
Glycaemic control directly correlates with the development of diabetic kidney disease and the rapidity of
progression to end-stage renal disease.[12] There is evidence that the use of sodium-glucose co-transporter
63
2 inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease)
in people with type 2 diabetes.[68] Optimisation of blood pressure control with the use of ACE inhibitors or
angiotensin-II receptor antagonist agents and reduction in proteinuria may slow the rate of progression to
ESRD and the eventual need for renal replacement therapy.
FOLLOW UP
Chronic kidney disease Guidelines
Diagnostic guidelines
United Kingdom
Chronic kidney disease: assessment and management (ht tps://

www.nice.org.uk/guidance/ng203)
Published by: National Institute for Health and Care Excellence Last published: 2021
International
KDIGO clinical practice guideline for the evaluation and management of

chronic kidney disease (ht tps://kdigo.org/guidelines)
Published by: Kidney Disease: Improving Global Outcomes Last published: 2013
GUIDELINES
North America
ACR appropriateness criteria: renal failure (ht tps://www.acr.org/Clinical-

Resources/ACR-Appropriateness-Criteria)
Published by: American College of Radiology Last published: 2020
65
Treatment guidelines
United Kingdom
Chronic kidney disease: assessment and management (ht tps://

Clinical practice guideline: exercise and lifestyle in chronic kidney

disease (ht tps://ukkidney.org/health-professionals/guidelines/guidelines-
commentaries)
Published by: Renal Association Last published: 2021
Anaemia of chronic kidney disease (ht tps://renal.org/health-professionals/

guidelines/guidelines-commentaries)
GUIDELINES
Haemodialysis (ht tps://renal.org/health-professionals/guidelines/guidelines-

commentaries)
Undernutrition in chronic kidney disease (ht tps://renal.org/health-

professionals/guidelines/guidelines-commentaries)
Renal replacement therapy and conservative management (ht tps://

International
KDIGO clinical practice guideline for the management of blood pressure in

KDIGO clinical practice guideline for diabetes management in chronic kidney

disease (ht tps://kdigo.org/guidelines)
KDIGO clinical practice guideline for the diagnosis, evaluation, prevention,

and treatment of chronic kidney disease-mineral and bone disorder (CKD-
MBD) (ht tps://kdigo.org/guidelines)
KDIGO clinical practice guideline for the evaluation and management of
GUIDELINES
KDIGO clinical practice guideline for lipid management in chronic kidney

disease (ht tps://kdigo.org/guidelines)
KDIGO clinical practice guideline for anemia in chronic kidney disease

(ht tps://kdigo.org/guidelines)
North America
Clinical practice guideline for nutrition in CKD: 2020 update (ht tps://
www.kidney.org/professionals/guidelines)
Published by: National Kidney Foundation Kidney Disease Outcomes Last published: 2020
Quality Initiative
Preservation of peripheral veins in patients with chronic kidney disease

(ht tps://www.avainfo.org/page/PositionPapers)
Published by: Association for Vascular Access Last published: 2011
67
Chronic kidney disease Online resources
Online resources
1. BMJ talk medicine: chronic kidney disease (https://soundcloud.com/bmjpodcasts/chronic-kidney-
disease?in=bmjpodcasts/sets/bmj-best-practice-clinical) (external link)
ONLINE RESOURCES
Chronic kidney disease Evidence tables
Evidence tables
What are the effects of calcium-containing phosphate binders versus calcium-
EVIDENCE TABLES
free phosphate binders in people with chronic kidney disease-mineral and
bone disorder (CKD-MBD)?[104]
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review)
that focuses on the above important clinical question.
View the full source guideline (https://kdigo.org/guidelines/ckd-mbd)
Evidence B * Confidence in the evidence is moderate or low to moderate where GRADE has been
performed and the intervention may be less effective or likely to be more harmful
than the comparison for key outcomes.
Population: Pre-dialysis or dialysis adults with hyperphosphatemic CKD ᵃ

Intervention: Calcium-containing phosphate binders
Comparison: Calcium-free phosphate binders
† ‡
Outcome Effectiveness (BMJ rating) Confidence in evidence (GRADE)
Mortality Favours comparison Moderate
Cardiovascular and See note ᵇ Low

cerebrovascular events
Recommendations as stated in the source guideline

The 2017 Kidney Disease Improving Global Outcomes (KDIGO) guideline on CKD-MBD makes the following
recommendation:
In adult patients with CKD (GFR category) G3a–G5D receiving phosphate-lowering treatment, we suggest
restricting the dose of calcium-based phosphate binders (weak recommendation; moderate-quality
evidence).
Note
ᵃ Population as reported by the guideline.
ᵇ The guideline reported results for this outcome narratively due to inconsistent results across studies. See
guideline for more information.
69
What are the effects of lower versus higher levels of serum phosphate or
calcium in people with chronic kidney disease (CKD) G3a-G5 or G5D?[104]

EVIDENCE TABLES
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review)
that focuses on the above important clinical question.
View the full source guideline (https://kdigo.org/guidelines/ckd-mbd)
Evidence C * Confidence in the evidence is very low or low where GRADE has been performed
and the intervention may be more effective/beneficial than the comparison for key
outcomes. However, this is uncertain and new evidence could change this in the
future.
Population: People with CKD G3a-G5 or G5D

Intervention: Lower concentrations of serum phosphate or calcium
Comparison: Higher concentrations of serum phosphate or calcium
† ‡
Outcome Effectiveness (BMJ rating) Confidence in evidence (GRADE)
Serum phosphate
Mortality Favours intervention Low
Glomerular Filtration Rate See note ᵃ Very Low

(GFR) decline
Cardiovascular and See note ᵇ Very Low

Serum calcium
Mortality Favours intervention Low
Cardiovascular and Favours intervention Low

Recommendations as stated in the source guideline

The 2017 Kidney Disease Improving Global Outcomes (KDIGO) guideline on CKD-MBD makes the following
recommendations:
• In patients with CKD (GFR category) G3a–G5D, treatments of CKD-MBD should be based on serial
assessments of phosphate, calcium, and parathyroid hormone (PTH) levels, considered together (not
graded).
• In people with CKD G3a-G5D, we suggest lowering elevated phosphate levels toward the normal
range (weak recommendation; low-quality evidence).
• In adult patients with CKD G3a–G5D, we suggest avoiding hypercalcaemia (weak recommendation;
low-quality evidence).
EVIDENCE TABLES
• In patients with CKD G3a–G5D, it is reasonable to base the frequency of monitoring serum calcium,
phosphate, and PTH on the presence and magnitude of abnormalities, and the rate of progression of
CKD (not graded).ᶜ
Note
The guideline only identified evidence from observational studies to answer this clinical question.
ᵃ Reported as inconclusive based on indirect evidence from 8 observational studies (N=3755).
ᵇ Reported as inconclusive based on direct evidence from 7 observational studies (N=34231).
ᶜ The guideline group also recommended reasonable monitoring intervals (not graded). See guideline for
more information.
* Evidence levels
The Evidence level is an internal rating applied by BMJ Best Practice. See the EBM Toolkit (https://
bestpractice.bmj.com/info/evidence-tables/) for details.
Confidence in evidence
A - High or moderate to high

B - Moderate or low to moderate
C - Very low or low
† Effectiveness (BMJ rating)

Based on statistical significance, which demonstrates that the results are unlikely to be due to chance, but
which does not necessarily translate to a clinical significance.
‡ Grade certainty ratings
High The authors are very confident that the true

effect is similar to the estimated effect.
Moderate The authors are moderately confident that
the true effect is likely to be close to the
estimated effect.
Low The authors have limited confidence in the
effect estimate and the true effect may be
substantially different.
Very Low The authors have very little confidence in
the effect estimate and the true effect is
likely to be substantially different.
BMJ Best Practice EBM Toolkit: What is GRADE? (https://bestpractice.bmj.com/info/toolkit/learn-ebm/what-
is-grade/)
71
Chronic kidney disease References
Key articles
• Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the
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evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013 Jan;3(1):1-150. Full
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• Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017 Mar
25;389(10075):1238-52. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/27887750?
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• Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: management of hyperglycemia in type
2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the
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• Chang AR, Lóser M, Malhotra R, et al. Blood pressure goals in patients with CKD: a review of
evidence and guidelines. Clin J Am Soc Nephrol. 2019 Jan 7;14(1):161-9. Full text (https://
cjasn.asnjournals.org/content/14/1/161) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/30455322?
• Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO 2017 clinical
practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney
disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017 Jul;7(1):1-59. Full text (https://
kdigo.org/wp-content/uploads/2017/02/2017-KDIGO-CKD-MBD-GL-Update.pdf)
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137. Levey AS, Beto JA, Coronado BE, et al. Controlling the epidemic of cardiovascular disease in chronic
renal disease: what do we know? What do we need to learn? Where do we go from here? National
Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis. 1998 Nov;32(5):853-906.
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patients. Am J Kidney Dis. 2005 Apr;45(4 Suppl 3):S1-153. Full text (https://www.ajkd.org/
issue/S0272-6386(00)X0194-1) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15806502?
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140. Warnock DG. Uremic acidosis. Kidney Int. 1988 Aug;34(2):278-87. Abstract (http://
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Contributors:
// Authors:
Manisha Singh, MD
Associate Professor
Division of Nephrology, Department of Internal Medicine, Director Home Dialysis Program, Co-Director M2
Renal Module, University of Arkansas for Medical Sciences, Little Rock, AR
DISCLOSURES: MS is an author of a reference cited in this topic.
Michelle W. Krause, MD, MPH

Professor of Medicine
Director, Integrated Medicine Service Line, Vice-Chair for Clinical Operations, Quality, and Efficiency,
Department of Internal Medicine, University of Arkansas for Medical Sciences, Central Arkansas Veterans
Healthcare System, Little Rock, AR
DISCLOSURES: MWK declares that she has no competing interests.
// Acknowledgements:
Dr Manisha Singh and Dr Michelle Krause would like to gratefully acknowledge Professor Sudhir V. Shah, a
previous contributor to this topic.
DISCLOSURES: SVS declares that he has no competing interests.
// Peer Reviewers:
Robert Toto, MD
Professor
Internal Medicine - Nephrology, Southwestern Medical School, The University of Texas Southwestern
Medical Center at Dallas, Dallas, TX
DISCLOSURES: RT declares that he has no competing interests.
Guy H. Neild, MD, FRCP, FRCPath

Professor of Nephrology
UCL Division of Medicine, University College London, London, UK
DISCLOSURES: GHN declares that he has no competing interests.

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Chronic kidney disease

Straight to the point of care

Last updated: Sep 13, 2022

The most common causes are diabetes mellitus and hypertension.

[BMJ talk medicine: chronic kidney disease] (https://soundcloud.com/bmjpodcasts/chronic-kidney-disease?

• Glomerular filtration rate (GFR) category is based on GFR (mL/minute/1.73 m²):

• G1 GFR ≥90: normal or high

History and exam

nausea with/without vomiting (common)

restless legs (common)

infection-related glomerular disease (uncommon)

Other diagnostic factors

enlarged prostate gland (common)

foamy-appearing urine (uncommon)

cola-coloured urine (uncommon)

age >50 years

childhood kidney disease

black or Hispanic ethnicity

family history of CKD

long-term use of non-steroidal anti-inflammatory drugs

high uric acid levels

wasting disorders, older or malnourished people).[1] GFR

urinalysis haematuria and/or

Other tests to consider

Condition Differentiating signs / Differentiating tests

Hypertensive • History of poorly controlled • Diagnostic tests include

reveals small, atrophic

Ischaemic nephropathy • History of long-standing • The urine sediment is

Condition Differentiating signs / Differentiating tests

Nephrotic syndrome • Often associated with a • Laboratory evidence may

Glomerulonephritis • Often associated with • Laboratory evidence

Condition Differentiating signs / Differentiating tests

GFR category G1 to G4 first-line therapy

GFR category G1 to G4 intolerant to first-line therapy

GFR category G3a/G3b

Treatment of anaemia and secondary hyperparathyroidism should be continued. It is recommended to

GFR category G5 and uraemia

Treatment algorithm overview

1st ACE inhibitor or angiotensin-II receptor

adjunct additional antihypertensive therapy

adjunct glycaemic control

2nd non-dihydropyridine calcium-channel

adjunct additional antihypertensive therapy

adjunct glycaemic control

GFR category G3 to G4 without

1st ACE inhibitor or angiotensin-II receptor

plus statin ± ezetimibe

adjunct additional antihypertensive therapy

adjunct glycaemic control

adjunct education about renal replacement

2nd non-dihydropyridine calcium-channel

plus statin ± ezetimibe

adjunct additional antihypertensive therapy

adjunct glycaemic control

adjunct education about renal replacement

with secondary plus dietary modification ± phosphate-binding

adjunct active vitamin D analogue

with metabolic acidosis adjunct oral sodium bicarbonate

GFR category G5 or with uraemia

with anaemia adjunct erythropoietin-stimulating agent