BJA Education, 22(8): 321e328 (2022)
doi: 10.1016/j.bjae.2022.03.005
Matrix codes: 1A01,
1A02, 1A03, 2A03,
2A05, 2A07, 3I00
Chronic kidney disease and anaesthesia
S.R. Chowdhury and H.A. McLure*
Leeds Teaching Hospitals NHS Trust, Leeds, UK
*Corresponding author. hamish.mclure@nhs.net
Keywords: anaesthesia; chronic kidney disease; perioperative management
Learning objectives
By reading this article, you should be able to:
 Describe the aetiology of chronic kidney disease
(CKD).
 Explain the pathophysiology of complications
relevant to anaesthesia for patients with CKD.
 Detail the changes in drug handling in CKD.
 Discuss the issues surrounding the perioperative
management of patients with CKD.
The importance of kidney function is reflected in the layers of
protection the body affords them. They have a vast reserve of
function, perfusion is maintained at the expense of other or-
gans and vulnerability to physical insult is reduced by
embedding the kidneys in a cushioning fat pad, high at the
back of the abdominal cavity within a protective bony cage.
With these defences, kidney failure represents overwhelming
damage that frequently includes other organs. The multi-
system pathology associated with kidney failure can have
profound effects on anaesthesia, so anaesthetists must know
how to assess these patients, when to investigate further and
how to treat the common complications.
Samina Chowdhury FRCA is a specialty registrar in anaesthesia in
Yorkshire, currently on a fellowship in Canada. Her clinical interests
include peri-operative medicine and anaesthesia for the high risk
surgical patient.
Hamish McLure FRCA is a consultant anaesthetist and medical di-
rector (Professional Standards & Workforce Development) at Leeds
Teaching Hospitals NHS Trust. He is past chairman of the Royal
College of Anaesthetists’ Clinical Director Network. His major clin-
ical interests are anaesthesia for renal transplantation, obstetrics
and providing long-term vascular access.
Accepted: 10 March 2022
Crown Copyright © 2022 Published by Elsevier Ltd on behalf of British Journal of Anaesthesia. All rights reserved.
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Advance Access Publication Date: 15 June 2022
Key points
 Chronic kidney disease has complications in
multiple systems.
 Coexistent cardiovascular disease is common.
 Management of CKD is centred around treating
reversible causes, slowing the rate of disease
progression and treating complications.
 Altered pharmacokinetics may result in drug
accumulation and toxicity.
 Fluid balance can be difficult to achieve and
should be monitored carefully.
Epidemiology
Chronic kidney disease (CKD) is common. More than 1.8
million people in the UK have a diagnosis of CKD with around
a further million thought to be undiagnosed. The estimated
disease prevalence in the UK of CKD stages 3e5 is thought to
be between 4.3% and 8.5% and this appears to be increasing.1
The global prevalence of CKD is 9.1%. In 2017, CKD was
recognised as the 12th leading cause of death, responsible for
1.2 million deaths each year worldwide. Deaths attributable to
CKD are set to increase further, with predictive modelling
suggesting that by 2040 2.2 million people will die annually
because of CKD. This is a best-case scenario. A worst-case
scenario would see a projection of up to 4 million people
dying. Such increases can in part be attributable to the in-
creases in the prevalence of risk factors such as diabetes and
hypertension.2
This disease is more common in smokers and certain
ethnic groups (Asian, African, Afro-Caribbean). The causes of
CKD are legion (Table 1).3 The most common causes are dia-
betes and hypertension. Hypertension is both a cause and
consequence of CKD.
Definition and classification
Chronic kidney disease is defined by the Renal Association as
an abnormality of kidney structure or function that lasts more
321
Management of chronic kidney disease

Table 1 Aetiology and risk factors for chronic kidney disease.

Relating to comorbidities Vascular disease including renal vascular stenosis

Hypertension
Type 2 diabetes mellitus
Intrinsic renal disease Glomerulonephritis
Acute kidney injury
Interstitial nephritis
Nephropathies Infective (e.g. pyelonephritis)
Obstructive (e.g. prostatic hypertrophy, nephrolithiasis)
Reflux
Genetic Polycystic kidney disease
Alport syndrome
Fabry disease
Cystinosis
Metabolic Hypercalcaemia
Hyperparathyroidism causing nephrocalcinosis
Oxalosis
Systemic disease Amyloidosis
Autoimmune disease Goodpasture syndrome
Scleroderma
IgA vasculitis
Systemic lupus erythematosus
Neoplasm Myeloma
Renal tumour
Toxins Lead poisoning
Drug-related NSAID use nephropathy
Calcineurin inhibitors
Chemotherapeutic agents
Other Haemolytic uraemic syndrome
Gout
Obstructive uropathy

than 3 months. It only becomes evident when fewer than 40%
of nephrons are functioning. Tests which enable diagnosis
include electrolyte abnormalities due to tubular disorders,
proteinuria (albumin to creatinine ratio (ACR) > 3 mg/mmol),
haematuria of renal origin, histological or radiological ab-
normalities in structure and abnormal function with resultant
raised creatinine and/or cystatin C (eGFR <60 ml/min/1.73 m2)
on more than two occasions 90 days apart.4 Additional ab-
normalities that may point to a diagnosis of CKD include
uraemia and anaemia. Classification aids risk stratification
and is based on eGFR and the presence of proteinuria (Fig 1).
Glomerular filtration rate (GFR) is the internationally
accepted measure to express renal function. However, GFR is
not routinely measured because it is a complex procedure that
involves measurement of plasma or urinary clearance of an
exogenous marker such as inulin. More commonly, eGFR is
used: this uses serum creatinine, cystatin, or both, age, and
sex to mathematically derive the eGFR. To date, there has
been a correction factor used for people of African-Caribbean
or African family origin. However, the most recent guidance
from the National Institute of Health and Care Excellence
(NICE) no longer recommends a correction factor for
ethnicity.5 Adjusting for ethnicity may overestimate actual
GFR and consequently result in an underdiagnosis of CKD in
black people.6
The 2021 CKD-EPI equation is recommended for calcula-
tion of eGFR. This is more accurate than other equations such
as the Modification of Diet in Renal Disease (MDRD) study
equation and the CockrofteGault equation for creatinine
clearance. The CKD-EPI equation can be used with or without
cystatin C. Cystatin C is a protein that is freely filtered at the
glomerulus, reabsorbed and metabolised by tubular cells.
Unlike creatinine, its metabolism is independent of muscle
mass. The inclusion of cystatin C in the CKD-EPI formula may
provide a more accurate estimate of GFR.7
Manifestations of renal impairment
Metabolic changes
The ability of the kidneys to excrete water and sodium is
impaired, causing difficulty in handling large fluid loads. As
glomerular filtration decreases, sodium and water are
retained and because of the increased hydrostatic pressure,
fluid moves into the extravascular space leading to the clinical
manifestations of fluid overload such as generalised and
pulmonary oedema. Paradoxically, the kidneys do not fare
well in the face of dehydration as renal hypoperfusion is a
common prerenal cause of acute kidney injury (AKI) and can
compound any pre-existing disease. The ability of the kidneys
to dilute or concentrate urine becomes progressively impaired
as CKD develops. Fluid balance is fragile and must be
managed carefully.8
Renal function is essential in electrolyte homeostasis, and
consequently CKD can cause metabolic disturbances including
hyperkalaemia, metabolic acidosis, hyperphosphataemia,
hypocalcaemia, hypermagnesaemia, hyperuricaemia and
hypoalbuminaemia. The most encountered and clinically
concerning metabolic disturbances in patients with severe

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 Management of chronic kidney disease

Persistent albuminuria categories

description and range

A1 A2 A3
Prognosis of CKD by GFR
and albuminuria categories: Normal to
Moderately Severely
KDIGO 2012 mildly
increased increased
increased

<30 mg g–1 30-300 mg g–1 >300 mg g–1

<3 mg mmol–1 3-30 mg mmol–1 >30 mg mmol–1

G1 Normal or high ≥90

GFR categories (ml min–1 1.73 m–2)

G2 Mildly decreased 60-89

description and range

Mildly to moderately
G3a 45-59
decreased

Moderately to
G3b 30-44
severely decreased

G4 Severely decreased 15-29

G5 Kidney failure <15

Figure 1 Classification of chronic kidney disease. GFR, glomerular filtration rate; CKD, chronic kidney disease; KDIGO, Kidney Disease: Improving Global Outcomes.

uncorrected renal disease are metabolic acidosis and hyper-
kalaemia. Metabolic acidosis results from a combination of
increased production of non-volatile acids, increased bicar-
bonate loss (and therefore decreased buffering capacity) and
decreased renal excretion of acid. Urinary bicarbonate loss is
caused by reduced tubular bicarbonate reabsorption. Ammo-
nium (and therefore acid) excretion is decreased because of the
reduction in GFR, which reflects a decline in the number of
functioning nephrons.9 Bicarbonate supplements are pre-
scribed to treat metabolic acidosis.
Loss of nephron function results in renal retention of po-
tassium. As GFR declines, the remaining nephrons adapt by
increasing renal excretion and this works as a compensatory
mechanism when the GFR is >15 ml min 1. Thereafter, extra-
renal mechanisms for handling potassium become vital: the
colon increases its capacity to excrete potassium. Saturation of
compensatory mechanisms leads to hyperkalaemia. The pro-
cess described is compounded by metabolic acidosis, which
causes potassium to move from the intracellular to the extra-
cellular compartment. Patients with coexistent diabetes may
be insulin deficient or insensitive, which limits the shift of
potassium to the intracellular space. Drug-induced hyper-
kalaemia is common in patients with CKD.10 The tendency
towards hyperkalaemia is ameliorated by instituting a low
potassium diet and avoiding drugs known to cause
hyperkalaemia.
Cardiovascular system
Hypertension is common in patients with CKD. This may be
the primary cause of the CKD or because of chronic salt and
water retention, excess renin production, or both.
Chronic kidney disease is associated with an increased risk
of ischaemic heart disease. Most patients do not progress to
end-stage renal failure but die as a result of fatal cardiovas-
cular complications (myocardial infarction, heart failure or
stroke).11 The underlying pathophysiological changes are
thought to be a combination of increased circulating inflam-
matory mediators, hypercoagulability, arterial calcification
and endothelial dysfunction.
Left ventricular hypertrophy can occur because of chronic
volume overload, pressure overload, or both. Volume overload
is caused by water and sodium retention, the presence of an
arteriovenous fistula or chronic anaemia leading to a hyper-
dynamic circulation with increased stroke volume and
tachycardia as a compensatory response. Pressure overload is
caused by hypertension and arteriosclerosis. The hypertrophy
is associated with myocardial fibrosis and impaired

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Management of chronic kidney disease
myocardial relaxation, which can lead to diastolic dysfunction
and arrythmias. Reduced left ventricular compliance results
in increased sensitivity to changes in volume.
Atherosclerosis is accelerated in patients with CKD. The
postulated mechanism involves impaired endothelial func-
tion, low-grade inflammation and dyslipidaemia. Changes in
lipoprotein metabolism result in an accumulation of interme-
diate density lipoprotein. Activation of the renineangiotensin
system leads to production of reactive oxygen species which
cause endothelial dysfunction and promote vascular remod-
elling. Dyslipidaemia is treated with statin therapy and this
reduces cardiovascular risk.
Patients undergoing renal replacement therapy (RRT) may
exhibit calciphylaxis, which describes accumulation of cal-
cium in small blood vessels. This is positively correlated with
vascular calcification and valvular heart disease.
Patients with CKD are predisposed to pulmonary oedema
because of fluid overload, left ventricular failure, or both.
Volume overload is treated with dietary sodium restriction
and diuretic therapy.
Severe uraemia can cause pericarditis.12
Respiratory system
The tendency towards development of fluid overload can cause
pulmonary oedema and pleural effusions, with a decrease in
pulmonary compliance, reduction in functional residual ca-
pacity and an increase in ventilationeperfusion mismatch.
Restrictive pulmonary dysfunction is common in patients
with CKD. This may be attributable to multisystem in-
teractions between the heart, kidneys and lungs involving
inflammation and protein-energy wasting (reduced capacity
for protein and energy storage). However, the exact patho-
physiology is yet to be elucidated.13
Haematological system
A reduction in the synthetic function of the kidney causes
lower levels of erythropoietin leading to anaemia. Guidance on
monitoring and treatment of anaemia in CKD varies between
institutions. Treatment modalities include iron supplementa-
tion (oral or intravenous) and intravenous erythropoiesis-
stimulating agents.14
Historically, patients with end-stage renal failure were
considered hypocoagulable. Acquired uraemic platelet
dysfunction and thromboasthenia decrease platelet adhesion
and increase vessel wall fragility, which contribute to bleeding
diatheses. Platelet function is abnormal because of decreased
adenosine diphosphate (ADP) content, impaired aggregation
to ADP, an increase in endogenous nitric oxide production, a
reduction in thromboxane A2 and defective interaction of von
Willebrand factor with platelet glycoprotein IIbeIIIa receptors.
Although skin bleeding time has been noted to be prolonged,
this has not been reflected in laboratory tests of coagulation
such as prothrombin time and activated thromboplastin time.15
Chronic kidney disease also represents a prothrombotic
state caused by decreased fibrinolysis, increased initial fibrin
formation, increased fibrineplatelet interaction and increased
qualitative platelet function. It is considered an independent
risk factor for venous thromboembolism (VTE). The risk of
VTE increases with decreasing eGFR, increasing age and other
more general risk factors such as immobilisation and
surgery.16
Haemostasis can be further complicated by underlying
disease, inherited coagulopathy and the use of drugs
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affecting blood clotting such as anticoagulants and anti-
platelet drugs.
Anaemia is common in end-stage renal failure, and pa-
tients may take erythropoiesis-stimulating agents such as
erythropoietin or darbepoetin alfa.
Gastrointestinal system
Symptoms of CKD such as anorexia, nausea, vomiting and
diarrhoea can render patients dehydrated. Poor nutritional
intake results in impaired wound healing in the postoperative
period. This can also be attributable to vascular disease and
underlying comorbidities such as diabetes and scleroderma.
Delayed gastric emptying may be a consequence of autonomic
neuropathy.
Central nervous system
Chronic kidney disease may result in a wide array of neuro-
logical manifestations including myoclonus, asterixis, chorea,
uraemic encephalopathy and seizures.
The incidence of seizures in patients with CKD is approx-
imately 10%.17 One third of patients with uraemic encepha-
lopathy exhibit provoked seizure activity. Metabolites of
creatinine are thought to be proconvulsant as they inhibit
gamma-aminobutyric acid (GABA) and stimulate N-methyl-D-
aspartate (NMDA) receptors, thus increasing calcium influx
into neurones and increasing cortical activity. Electrolyte
imbalance is also important in the pathophysiology of sei-
zures in CKD as changes in extracellular ion concentration
influence the activity of voltage-gated ion channels.
Dialysis disequilibrium syndrome is a rare form of tran-
sient encephalopathy that is usually precipitated by rapid or
omitted dialysis sessions. Although the exact cause is un-
known, it is thought to be caused by the relatively faster
clearance of urea from plasma relative to that from the brain.
The association between recombinant human erythropoietin
and seizures is uncertain; however, it was once considered a
risk factor for seizures. Certain classes of antibiotics can cause
cortical irritability and may contribute to seizure develop-
ment. These include penicillins, cephalosporins, carbape-
nems and quinolones.
Autonomic neuropathy is common in patients with CKD
because of decreased baroreceptor sensitivity, sympathetic
overactivity and parasympathetic dysfunction. Blood pressure
control may be difficult to achieve, and the patient may be
predisposed to the development of perioperative arrhythmias.
Uraemia, type 2 diabetes mellitus and hyperparathyroidism all
contribute to the pathogenesis of autonomic neuropathy.
Endocrine system
Deterioration in renal function leads to reduced synthesis of
the active form of vitamin D, 1,25-dihydroxycholecalciferol
(calcitriol). This leads to impaired calcium reabsorption from
the gastrointestinal tract and the kidneys. An increase in
serum phosphate (from failure of excretion) also contributes
to hypocalcaemia, which stimulates production of para-
thyroid hormone (PTH); over time, parathyroid hyperplasia
ensues with pathologically raised PTH levels. This secondary
hyperparathyroidism leads to bone demineralisation and a
consequent increase in the risk of fractures.
Phosphate retention may necessitate the use of dietary
phosphate restriction and phosphate binders. Vitamin D an-
alogues and calcimimetics suppress the secretion of PTH.

Decreased sensitivity to insulin can worsen glycaemic
control.18
Management of CKD
The principles of management around CKD are based on
treating reversible causes, preventing or slowing progression
of the disease, managing complications and identifying pa-
tients requiring RRT.19
Prevention of AKI and subsequent progression to CKD
Renal hypoperfusion may occur because of hypovolaemia,
hypotension or infection. The anaesthetist therefore has an
important role in the prevention of AKI in the perioperative
period. Stopping nephrotoxic drugs such as aminoglycoside
antibiotics, NSAIDs and radiographic contrast should be
considered. Relief of urinary tract obstruction may also
reverse the disease process.
Slowing the rate of progression
The main targets for renal protection are optimal blood
pressure control and control of proteinuria. This is largely
achieved using angiotensin-converting enzyme (ACE) in-
hibitors or angiotensin II receptor blockers. Treatment of hy-
pertension also reduces the rate of cardiovascular
complications. The optimal blood pressure target should be
individualised, taking into account comorbidities such as
diabetes.
Diet plays an important part in slowing the rate of pro-
gression in CKD. The recommended daily energy intake is
30e40 kcal kg 1 ideal body weight (IBW) per day with adjust-
ments needed to consider age and physical activity. Nutri-
tional supplementation may be required. The minimum
protein intake for a patient with CKD stage 4e5 who is not on
dialysis is 0.8 g kg 1 IBW day 1. Sodium intake should be
restricted to <2.4 g day 1. Patients with hyperkalaemia,
hyperphosphataemia, or both may need to restrict their di-
etary potassium and phosphate intake, respectively. It is
therefore imperative that patients have access to expert
advice from a dietitian as part of a multidisciplinary
approach.20
Renal replacement therapy
The options for managing end-stage renal failure include
conservative management focussed on achieving symptom
control, RRT and renal transplantation.
Patients with CKD stage 5 (GFR <15 ml min 1) are usually
referred to a nephrologist for discussion regarding further
management. There are no absolute criteria for commence-
ment of RRT in this setting and decisions regarding treatment
options are made in close collaboration with the patient.
Renal replacement therapy comprises either dialysis,
which can be peritoneal dialysis (PD) or haemodialysis, or
kidney transplantation.
In PD, the peritoneum is used as the membrane through
which fluid and dissolved substances are exchanged with the
blood. Dialysate is infused in the peritoneal cavity. This dial-
ysate contains sodium chloride, lactate or bicarbonate and a
high concentration of glucose ensuring hyperosmolarity.
Proteins and electrolytes are exchanged over the membrane
and the exchange of water is driven by osmosis. This is
considered a more ‘lifestyle-friendly’ method of RRT and al-
lows patients to be treated at home or in an ambulatory
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Management of chronic kidney disease
context, and obviates the need for invasive vascular access. It
is not without complications, some of which include perito-
nitis, hyperglycaemia, weight gain, hernias and back pain.
Encapsulating peritoneal sclerosis (EPS) is a rare but poten-
tially fatal complication of PD. It occurs because of thickening
and sclerosis of the peritoneum, which can cause bowel
obstruction.
In haemodialysis, dialysate is pumped in a counter-current
direction to blood flow and solutes equilibrate after diffusion
across a semipermeable membrane. This too has associated
complications, which include those related to vascular access,
hypotension, arrhythmias and dysequilibration syndrome.
Kidney transplantation from either a cadaveric or living
donor provides the best outcomes and should be considered
for all patients with CKD stage 5. At induction of anaesthesia
for renal transplantation, patients require antibodies directed
against T cells such as basiliximab or alemtuzumab. Trans-
plant recipients also require long-term maintenance immu-
nosuppression to prevent rejection.
A comprehensive overview of RRT modalities is outside the
scope of this article, but further information can be found in
the referenced text.21
Vascular access
Haemodialysis necessitates vascular access, and there are
several methods that the anaesthetist should be familiar
with.22 The type of vascular access device may be temporary
or more permanent depending on clinical need. Temporary
vascular access can be achieved by short-term lines, tunnelled
and cuffed lines and subcutaneous port catheter systems.
Guidance suggests that acute short-term non-cuffed lines
should not be used for longer than 1 week because of the risk
of infection. The most common site for temporary vascular
access is the right internal jugular vein because of its relative
ease of access, a lower risk of stenosis than the left internal
jugular vein and subclavian routes, and a lower risk of infec-
tion than the femoral route.
More permanent vascular access solutions include native
arteriovenous fistulae (the vascular access of choice), arte-
riovenous grafts or long-term catheters.
Complications related to vascular access include infection,
stenosis, thrombosis and aneurysm.
Pharmacology
Pharmacokinetics
Absorption
Gastroparesis leads to delayed gastric emptying.23 Drugs may
therefore take longer to reach peak plasma concentrations.
Fluid overload can lead to small bowel oedema, which may
result in delayed absorption. An increase in gastric pH occurs
as a result of the action of gastric urease which converts urea
to ammonia. As a result, the degree of drug ionisation is
altered and this may affect drug bioavailability.
Distribution
The volume of distribution (VD) of a drug is influenced by total
body water, protein binding and tissue binding. All of these
variables are affected by CKD. Protein binding of acidic drugs
is reduced as a result of hypoalbuminaemia, conformational
changes in protein binding sites and competition for binding
sites with organic acids. Conversely, there is an increase in the
plasma concentration of alpha1-acid glycoprotein, which is
BJA Education - Volume 22, Number 8, 2022 325
Management of chronic kidney disease
the main binding site for basic drugs. Hydrophilic drugs
exhibit an increase in VD (and tissue binding) owing to fluid
retention in patients with CKD. As the extracellular fluid vol-
ume increases, the serum concentration of a given drug may
decrease. This should be considered when calculating loading
doses in patients with CKD.
Metabolism
Cytochrome P450 (CYP) activity may be altered in the context
of severe CKD. The effect is different on different isoenzymes:
CYP3A4 and CYP2C9 are inhibited whereas CYP2E1 is induced.
Excretion
Drugs that are normally excreted renally may accumulate.
The extent of the accumulation depends on the degree to
which the drug is dependent on renal excretion compared
with non-renal clearance. Interestingly, non-renal clearance
of many drugs is also reduced. Dose changes are required for
many drugs in CKD, and creatinine clearance is often used to
aid dosage modifications depending on the severity of renal
impairment.
Chronic kidney disease and anaesthesia
Preoperative considerations
History and examination
In addition to the general preoperative evaluation, there are
specific points of attention in patients with CKD:
(i)Aetiology of the CKD
(ii)Severity of renal impairment (clinical and biochemical)
(iii)Fluid status, dry weight, ability to produce urine
(iv) Renal replacement therapy: modality, last session,
amount of fluid removed
(v) Drug history, paying particular attention to immuno-
suppressant and long-term steroid therapy (may require
perioperative steroid replacement)
The presence of an arteriovenous fistula should be noted.
Repeated attempts at vascular access cause patients with CKD
to have thrombosed and fragile vasculature. Invasive vascular
access may be required. Capillary refill time, skin turgor and
auscultatory findings are a handful of clinical signs that may
provide clues regarding the patient’s volaemic status.
Clinical investigations
All patients with CKD should have a full blood count and urea
and electrolytes measured. The full blood count will reveal
anaemia and the biochemistry tests will aid quantification of
CKD severity. Coagulation studies can be helpful in patients
where coagulopathy is suspected, and there is the potential
for perioperative bleeding. However normal coagulation
studies do not preclude thrombopathy.
Where there is clinical evidence of fluid overload, a chest
X-ray is indicated to visualise pleural effusions. A patient with
suspicion of cardiac impairment or pericardial effusion
should have echocardiography. All patients should have an
ECG to screen for left ventricular hypertrophy, ischaemia and
arrythmias.
Preoperative management
Disease-specific treatment should be continued throughout
the perioperative period where it is safe and practicable to do
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so. Certain medications such as ACE inhibitors remain
controversial in the preoperative setting with no consensus
regarding whether preoperative ACE inhibitor therapy is
beneficial or harmful. Therefore, preoperative antihyperten-
sive management should be considered on an individual basis
and remains at the discretion of the anaesthetist. Should a
patient require dialysis before surgery, liaise with the pa-
tient’s specialist team.
Conduct of anaesthesia
In addition to the minimum monitoring standards set out by
the Association of Anaesthetists, the use of more invasive
monitoring should be considered Those patients who have
poor blood pressure control before surgery may benefit from
the insertion of an arterial line. Prolonged major surgery may
also be an indication for invasive arterial pressure monitoring.
Central venous access may be required because peripheral
venous access is poor, to facilitate the use of potent vasoactive
drugs and can aid in assessment of the patient’s fluid status.
Care should be taken to preserve arteriovenous fistulae and to
protect potential fistula sites. As such, forearms veins should
be avoided where possible. Arteriovenous fistulae should be
carefully wrapped in cotton wool and the non-invasive blood
pressure cuff placed on the opposite arm. Urine output
monitoring is an important modality in assessing end organ
perfusion and is even more valuable in the context of CKD.
Gastroparesis because of autonomic dysfunction may
necessitate a rapid sequence induction. A modified approach
should be used with rocuronium and sugammadex reversal if
required. For intraoperative muscular relaxation, atracurium
or cisatracurium are the drugs of choice. In general, drugs
with shorter half-lives and drugs that do not depend on renal
elimination should be used in order to prevent accumulation.
Inhalational agents
Production of inorganic fluoride from the metabolism of vol-
atile anaesthetics, particularly methoxyflurane, by the he-
patic cytochrome P450 system is known to cause vasopressin-
resistant high-output renal insufficiency. Animal and human
studies have demonstrated that neither the peak value of
fluoride nor the duration of systemic fluoride exposure
correlate with anaesthetic nephrotoxicity.24
There has been much discussion and research regarding
sevoflurane and the production of potentially toxic chemicals
(compounds A, B, C, D and E) that are produced when sevo-
flurane is used in the presence of carbon dioxide absorbents.
When sevoflurane encounters soda lime absorbers, it un-
dergoes dehydrofluorination to form haloalkenes (called
compound A). Compound A has been shown to be severely
nephrotoxic in rats. However, the concentration of these
compounds produced in clinical practice is insufficient to
induce nephrotoxicity. As such, sevoflurane is considered safe
in CKD.
Desflurane and isoflurane are metabolised to a minimal
extent and there are no concerns regarding their use in CKD.
Neuromuscular blocking agents
Atracurium is the neuromuscular blocking agent (NMBA) of
choice in patients with CKD. Its metabolism is unique. Atra-
curium undergoes ester hydrolysis and Hofmann degrada-
tion, both of which are independent of renal function.
Cisatracurium can also be used in patients with CKD. It is

predominantly eliminated by Hofmann degradation. Its
clearance is reduced by 13% in CKD, and its terminal elimi-
nation half-life is increased by 4.2 min. The cisecis isomer of
mivacurium may accumulate and result in slower sponta-
neous recovery of neuromuscular block. An adjustment in the
rate of infusion should be considered. Up to 30% of vecuro-
nium is excreted renally. Therefore, its duration of action is
increased, and its clearance is reduced in patients with CKD.
Infusions or repeat boluses may accumulate. Up to a third of
rocuronium is excreted renally in a 24-h period. Its clearance
is reduced by 39% in CKD therefore prolonging time to re-
covery. The effects of rocuronium become less predictable in
renal failure. Pancuronium has reduced clearance and a pro-
longed half-life in those with CKD and so is best avoided.
Suxamethonium should be avoided because of the risk of
exacerbating pre-existing hyperkalaemia.
Sugammadex has been used successfully in clinical
research to reverse blockade from aminosteroid NMBAs in
patients with severe renal impairment. The sugammadexe
rocuronium complex can persist in vivo for up to 7 days. The
rocuroniumesugammadex complex is very stable and can be
cleared by high-flow dialysis.25
Opioid analgesics
Opioids have no direct nephrotoxic effects. They do have an
antidiuretic effect, which may manifest clinically as urinary
retention.
The metabolite responsible for the potent analgesic,
sedative and respiratory depressant effects of morphine is
morphine-6-glucuronide. Its elimination is dependent on
renal function, and its half-life is prolonged from 2 to 27 h in
patients with CKD. Therefore, an appropriate dose reduction
should be considered. Approximately 7% of fentanyl is
excreted unchanged in the urine. Its clearance is reduced in
CKD. In the context of renal failure, alfentanil is less protein
bound and there is therefore a greater amount of free drug
available to exert its effect. A dose reduction may be neces-
sary. Remifentanil is not dependent on renal function for its
elimination. Both oxycodone and its metabolites accumulate
in patients with CKD with a related prolongation in elimina-
tion half-life of 2.3e3.9 h. This may necessitate a dose
reduction and an increase in dose interval. Tramadol is 30%
excreted unchanged in the urine. It may be epileptogenic in
the context of uraemia because of the lowered seizure
threshold. The elimination half-lives of codeine and dihy-
drocodeine are significantly prolonged, and these drugs
should therefore be used with caution.
Non-steroidal anti-inflammatory drugs
The nephrotoxic potential of NSAIDs is well known, and as
such this class of drug should be avoided in the patient with
CKD. Such drugs reduce renal blood flow and GFR and may
also cause acute interstitial nephritis. They can increase the
risk of major vascular events and increase the risk of bleeding
in a group of patients who may have an element of coagul-
opathy because of uraemia and platelet dysfunction. Non-
steroidal anti-inflammatory drugs have a harmful effect on
potassium excretion and can contribute to hyperkalaemia.
Regional anaesthesia
Regional anaesthesia is a useful way of avoiding systemic
drug accumulation and can be used as the primary anaes-
thetic technique, depending on the type of surgery. Central
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Management of chronic kidney disease
neuraxial blockade is not absolutely contraindicated, but
consequent hypotension must be attended to in order to
prevent worsening of renal perfusion and further worsening
in renal function. Blood pressure should be maintained with
vasoconstrictors and fluid preloading should be carried out
judiciously to prevent precipitating fluid overload. Coagula-
tion abnormalities must be borne in mind and might pose a
contraindication to spinal or epidural anaesthesia.
Irrespective of the technique and drugs used, it is essential
to maintain normovolaemia and renal perfusion pressure.
Blood pressure targets should be individualised for the patient
using preoperative baseline readings as an estimate.
Careful fluid balance extends to the postoperative period.
Patients may require dialysis. Patients with CKD are vulner-
able to the sedative effects of opioids amongst other drugs and
can take longer to emerge from anaesthesia with more pro-
longed residual drowsiness. They may therefore require an
extended period of supplemental oxygen therapy and
continuous oxygen saturation monitoring.
Declaration of interests
The authors declare that they have no conflicts of interest.
MCQs
The associated MCQs (to support CME/CPD activity) will be
accessible at www.bjaed.org/cme/home by subscribers to BJA
Education.
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