PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

Perioperative management of
the patient with chronic
kidney disease

setting of CKD is a serious complication that is associated with

considerable morbidity and mortality.

Aetiology
A gradual fall in renal function is a normal consequence of
ageing, but rarely results in ESRF. The two most common
medical conditions associated with CKD are diabetes mellitus
and arterial hypertension. Control of the underlying condition
(Box 1) is crucial in preventing further deterioration of renal
function.

Mark Dougherty
Stephen T Webb

Multi-system effects

Abstract
The prevalence of chronic kidney disease (CKD) is increasing. Perioperative management of patients with CKD aims to control modifiable risk
factors associated with acute kidney injury (AKI). AKI on the background
of CKD may lead to dialysis dependency. CKD has widespread cardiovascular, endocrine, metabolic and haematological effects. Preoperative
assessment and preparation require multidisciplinary input from the
surgical, anaesthetic and nephrology teams. Perioperative care should
ensure the correction of hypovolaemia, maintenance of renal blood
flow and perfusion pressure, prevention of radiocontrast-induced nephrotoxicity, avoidance of nephrotoxic drugs and treatment of urinary tract
obstruction.

The widespread multi-system effects of CKD reflect the functions

of the kidney (Box 2).
Fluid overload
Sodium and water retention occurs as functional nephrons are
lost. Perioperative fluid restriction may be necessary for fluid
overloaded patients.
Electrolyte derangement
Hyponatraemia or hypernatraemia reflects the combination of
impaired renal handling of sodium and water. Hyperkalaemia
results from reduced renal secretion, metabolic acidosis and coexisting use of angiotensin-converting enzyme (ACE) inhibitors
and angiotensin receptor blockers (ARBs).

Keywords Acute kidney injury; chronic kidney disease; nephrotoxicity;

renal blood flow

Anaemia
The anaemia associated with CKD is multifactorial in origin.
Dietary haematinic deficiency (e.g. iron, folate and vitamin B12),
occult gastrointestinal blood loss and impaired renal erythropoietin production all contribute to the development of anaemia.
Patients with CKD are often treated with erythropoietin. Blood
product transfusion is avoided if possible, to prevent red cell
allosensitization reducing the success of renal transplantation.

Introduction
Chronic kidney disease (CKD) is a progressive, multi-system
condition that encompasses a wide clinical spectrum (Table 1)
ranging from entirely normal renal function to end-stage renal
failure (ESRF). It is postulated that renal function gradually
deteriorates as a result of an underlying predisposition or some
other renal insult. The rate and extent of deterioration varies
between individuals and depends on the aetiology of the renal
impairment.
The most recent UK Renal Registry report suggests that the
incidence of CKD requiring renal replacement therapy (RRT) is
w100 per million of population, and that the prevalence of stage
5 CKD is increasing by >4% per year. The prevalence of CKD
stages 3e5 is around 5%. Because the majority of individuals are
asymptomatic, the prevalence of CKD stages 1e2 is unknown,
but likely to be significant.
The aim of perioperative management is to control factors that
may result in acute kidney injury (AKI) and a further decline in
renal function (Table 2). The onset of perioperative AKI in the

Coagulopathy
Although routine laboratory coagulation test results may be
normal, platelet dysfunction is often present and the bleeding
time may be prolonged. Platelet dysfunction may be treated by

Stages of chronic kidney disease

Stage

Degree of impairment

GFR (ml/min/1.73 m2)

Normal function, but structural

or genetic disposition
to kidney disease
Mildly reduced function with
findings of stage 1
Moderately reduced function
Severely reduced function
End-stage renal disease or
dialysis dependant

>90

2
3
4
5

Mark Dougherty MB BCh BAO MRCP FCARCSI is a Specialist Registrar in

Anaesthesia at The Royal Hospitals, Belfast, UK. Conflicts of interest:
none declared.
Stephen T Webb MB BCh BAO FRCA EDIC is a Consultant in Anaesthesia &
Intensive Care Medicine at Papworth Hospital, Cambridge, UK. Conflicts
of interest: none declared.

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60e89
30e59
15e29
<15

GFR, glomerular filtration rate

Table 1

433

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PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

Classification and staging system for acute kidney

injury
Stage

Serum creatinine criteria

Urine output criteria

Increase in serum
creatinine
0.3 mg/dl
(
26.4 mmol/litre) OR
Increase to more than
or equal to 150%e200%
(1.5e2-fold) from baseline
Increase in serum creatinine
to more than 200%e300%
(>2e3-fold) from baseline
Increase in serum creatinine
to more than 300% (>3-fold)
from baseline OR
Serum creatinine
4.0 mg/dl
(
354 mmol/litre) with an
acute increase >0.5 mg/dl
(>44 mmol/litre)

<0.5 ml/kg/hour for

6 hours

Functions of the kidney

Regulation of water and electrolytes
Maintenance of acidebase balance
Excretion of metabolic waste products and water-soluble drugs
Endocrine functions e erythropoietin, renin, vitamin D

Box 2
<0.5 ml/kg/hour for
12 hours
<0.3 ml/kg/hour for
24 hours
OR Anuria for
12 hours

retention, or secondary to excessive renin production or renal

artery stenosis. The autoregulation plateau, within which renal
blood flow is largely independent of perfusion pressure, is shifted
to the right, making the kidneys more susceptible to renal
hypoperfusion at comparatively normal blood pressures.
Hypertension and impaired calcium handling leads to accelerated
occlusive arterial disease. Co-existing coronary, cerebral and
peripheral arterial disease is common.

Note: given wide variation in indications and timing of initiation of renal

replacement therapy (RRT), individuals who receive RRT are considered to
have met the criteria for stage 3 irrespective of the stage they are in at the
time of RRT

Immunosuppression
Immune function, particularly phagocytosis and chemotaxis, is
impaired in CKD. Protein-losing nephropathy may result in
increased excretion of immunoglobulins. Patients with CKD are
therefore prone to infection and impaired wound healing.

Table 2

Malnutrition
Malnutrition in CKD is complex. Uraemic malnutrition may be
secondary to a decrease in the renal excretion of the so-called
satiety protein leptin. Increased leptin levels suppress insulin
release and favour protein catabolism. Increased oxidative stress,
and impaired gluconeogenesis and protein metabolism all
contribute to malnutrition. Malnutrition further increases the
risks of infection and impaired wound healing.

the use of erythropoietin or efficient dialysis. Desmopressin

(1-deamino-8-D-arginine vasopressin; DDAVP) may be used in
the perioperative period to temporarily reduce the bleeding time
by mobilizing von Willebrand factor.
Renal osteodystrophy
Phosphate retention and impaired vitamin D production results
in reduced calcium absorption from the gastrointestinal tract and
subsequent hypocalcaemia. Hypocalcaemia increases parathormone production (secondary hyperparathyroidism), which
increases bone resorption. Renal osteodystrophy causes bone
pain and proximal myopathy, and predisposes to pathological
fractures. Special care must be taken during patient positioning
in order to avoid injury.

Peripheral neuropathy
Uraemic neuropathy is predominantly a peripheral sensorimotor
polyneuropathy. There is a risk of pressure-induced peripheral
neuropathy during anaesthesia.
Disordered drug excretion
Inappropriate drug dosing in CKD is an important cause of
inadvertent adverse effects. Impaired renal function results in
reduced glomerular filtration and reduced tubular excretion. The
accumulation of uraemic toxins alters the degree of plasma
protein binding and therefore affects the plasma levels of acidic
drugs. The level of a1 acid-glycoprotein is increased in CKD
leading to increased binding of basic drugs and reduced plasma
levels. Alteration in drug doses or intervals will often be required
in patients with CKD.

Cardiovascular dysfunction
Hypertension may be both the cause and consequence of CKD.
Hypertension may be idiopathic, related to sodium and water

Causes of chronic kidney disease

Diabetes mellitus
Hypertension
Renal vascular disease
Glomerulonephropathy
Tubulointerstitial disease
Hereditary conditions
Obstructive uropathy

Preoperative assessment
Clinical assessment
The management of patients with renal dysfunction requires the
collaboration of the surgical, anaesthetic and nephrology teams.
As well as establishing the aetiology and severity of CKD, it is
important to identify the presence of co-existing conditions. The
volume of daily urine output, usual body weight and requirement

Box 1

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PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

Correction of hypovolaemia
Intravascular volume depletion may be avoided by monitoring
fluid intake and output, repeated observation of clinical signs and
the appropriate use of invasive haemodynamic monitoring. Perioperative hypovolaemia should be rapidly but judiciously corrected by volume expansion with intravenous fluids. The choice of
fluid is a matter for personal preference and remains the subject of
debate. With the exception of Hartmanns solution, which contains
lactate, all isotonic crystalloids can be used safely in CKD. The
safety and long-term consequences of the use of synthetic colloids
(e.g. gelatinins and hydroxyethyl starch) in CKD have not yet been
fully elucidated. A balanced approach, using a combination of
crystalloid maintenance and colloid is recommended.

for daily fluid restriction should be evaluated. An assessment

should be made of renal replacement therapy (RRT) access, type
and schedule. Ideally, surgery should be scheduled to minimize
interruption to RRT. Vascular access and non-invasive blood
pressure measurement should be avoided in limbs where an
arteriovenous fistula has been created for dialysis. Determining
drug regimens, and ensuring the continuation of essential
medication with minimal adverse effect to the fluid, electrolyte
and haemodynamic status of the patient.
Laboratory tests
A full blood count will determine the presence and severity of
anaemia or thrombocytopaenia. The bleeding time should be
measured as coagulation studies are likely to be within normal
limits. Baseline serum electrolyte (Na, K, Ca2, Mg2, Cl),
urea and creatinine levels should be recorded.

Maintenance of renal perfusion

The maintenance of adequate renal perfusion requires the
defence of both cardiac output and systemic arterial pressure. The
initial approach should be intravascular volume expansion to
correct hypovolaemia. Inotropic and vasopressor therapy may
then be initiated for the management of low cardiac output and
systemic arterial hypotension respectively. Dopamine or dobutamine may be used to improve cardiac output and mean arterial
pressure but have no specific renal protective effect. Noradrenaline
is an effective first-line vasopressor agent. There is no firm
evidence to suggest that the drug compromises renal, hepatic or
gastrointestinal blood flow when used to treat arterial hypotension. The optimal therapeutic target for systemic arterial pressure
for renal protection has not been established. A minimum mean
arterial pressure of 65e75 mmHg is often quoted, however a higher
target may be necessary in patients with pre-existing hypertension.

Electrocardiogram
The resting 12-lead electrocardiograph (ECG) may demonstrate
the presence of established myocardial infarction, uraemic pericarditis or cardiac chamber hypertrophy. Exercise ECG testing or
cardiopulmonary exercise testing may be required.
Chest radiography
Chest radiography may demonstrate cardiomegaly, pulmonary
venous congestion or metastatic calcification.

Perioperative management
Modifiable factors should be controlled to prevent AKI in patients
with CKD (Table 3):
 correction of hypovolaemia
 maintenance of renal perfusion pressure and blood flow
 prevention of radiocontrast-induced nephrotoxicity
 avoidance of nephrotoxic drugs
 treatment of urinary tract obstruction.

Prevention of radiocontrast-induced nephropathy

The benefit of isotonic intravascular volume expansion for the
prevention of radiocontrast-induced nephropathy has been
clearly demonstrated. However, the ideal composition of such
fluid and the optimal rate of infusion have not been determined
and should be individualized. Both sodium chloride 0.9% and

Risk factors for acute kidney injury

Preoperative factors
Chronic disease
- Advanced age
- Female sex
- Chronic renal disease
- Diabetes mellitus
- Chronic cardiac failure
- Aortic and peripheral vascular disease
- Chronic liver disease
- Genetic predisposition

Intraoperative factors
Type of surgery
- Cardiac
- Aortic
- Peripheral vascular
- Non-renal solid organ transplantation
Other factors
- Emergency surgery
- Aortic clamp placement
- Intra-operative radiocontrast

Postoperative factors
Acute conditions
- Acute cardiac dysfunction
- Haemorrhage
- Hypovolaemia
- Sepsis
- Rhabdomyolysis
- Intra-abdominal hypertension
- Multiple organ dysfunction syndrome
- Drug nephrotoxicity

Acute conditions
- Hypovolaemia
- Sepsis
- Multiple organ dysfunction syndrome
- Drug nephrotoxicity
Table 3

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PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

gentamicin, vancomycin) and the use of lipid formulations of

amphotericin B have been demonstrated to reduce the risk of
nephrotoxicity associated with these drugs. Recently, concerns
were raised about the risk of AKI associated with the use of the
antifibrinolytic agent aprotinin in cardiac surgery. Evidence
suggests that the use of aprotinin during coronary artery bypass
graft surgery may be associated with an increased risk of AKI
requiring RRT. The potential for drug-induced nephrotoxicity
must be balanced against the therapeutic benefits and the clinical
context.

Perioperative renal protection in chronic kidney

disease
Preoperative
- Optimize volume status, cardiac output and systemic arterial
pressure
- Withhold nephrotoxic drugs
- Maintain glycaemic control in diabetic patients
- Correct metabolic and electrolyte disturbances
- Arrange preoperative dialysis for dialysis-dependent patients
- Administer isotonic intravenous fluids for prevention of
radiocontrast-induced nephropathy

Urinary tract obstruction

The early diagnosis and institution of therapeutic measures to
overcome urinary tract obstruction are important. Urinary catheterization is required to accurately assess urine output and
ultrasound imaging is necessary to identify the presence and site
of obstruction. Early urology consultation is recommended.

Intraoperative
- Optimize volume status, cardiac output and systemic arterial
pressure
- Avoid nephrotoxic drugs
- Maintain glycaemic control in diabetic patients

Renal replacement therapy

The optimal type and timing of RRT in AKI superimposed on
CKD is unclear. The presence of pulmonary oedema, refractory
hyperkalaemia, metabolic acidosis or clinical features of uraemia
should be taken as absolute indications for RRT. Clinical
outcomes may be improved if RRT is commenced early. A
summary of perioperative renal protection measures in CKD is
given in Box 3.
A

Postoperative
- Avoid nephrotoxic drugs
- Maintain glycaemic control in diabetic patients
- Promptly treat acute cardiac dysfunction
- Control haemorrhage
- Manage sepsis aggressively
- Recognize and treat rhabdomyolysis
- Recognize and treat intra-abdominal hypertension
- Provide appropriate organ support for multiple organ
dysfunction syndrome
- Institute renal replacement therapy if required for acute
kidney injury
- Recommence dialysis for dialysis-dependent patients

FURTHER READING
Acute Kidney Injury Network (AKIN), http://www.akinet.org/.
Kidney Disease: Improving Global Outcomes (KDIGO) guidelines,
http://www.kdigo.org/clinical_practice_guidelines/index.php.
National Kidney Foundation Kidney Disease Outcome Quality Initiative
(NKF KDOQI) guidelines, http://www.kidney.org/professionals/kdoqi/
guidelines_commentaries.cfm.
NICE guidance: chronic kidney disease, http://guidance.nice.org.uk/CG73.
UK Renal Association (UKRA) guidelines, http://www.renal.org/Clinical/
GuidelinesSection/Guidelines.aspx.
UK Renal Registry, http://www.renalreg.com.
Webb ST, Allen JSD. Perioperative renal protection. Cont Educ Anaesth Crit
Care Pain 2008; 8: 176e80.
Zacharias M, Conlon NP, Herbison GP, Sivalingam P, Walker RJ,
Hovhannisyan K. Interventions for protecting renal function in the
perioperative period. Cochrane Database Syst Rev 2008 Oct 8; (4):
CD003590.

Box 3

sodium bicarbonate 4.2% appear to be effective. The use of

N-acetylcysteine to prevent radiocontrast-induced nephropathy
remains the subject of ongoing investigation. Patients with CKD
who require radiocontrast will benefit from the use of the lowest
possible volume of non-ionic, iso-osmolar contrast in conjunction with isotonic intravenous fluids.
Avoidance of nephrotoxic drugs
Minimizing exposure to nephrotoxic drugs is crucial in patients
with CKD. The use of once-daily aminoglycoside dosing (e.g.

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