Download Acute renal dysfunction or failure is a common occurrence in the

INTRODUCTION
Acute renal dysfunction or failure is a common occurrence in the intensive care unit (ICU).
The reported incidence of acute renal failure in the ICU varies and is dependent upon
several factors including:



Definition of acute renal failure (this will be discussed later)
Case mix of patients
Whether the reported series is from a secondary or tertiary referral centre.
The incidence of acutely impaired renal function is very high in those patients dying in the
ICU with sepsis or multiple organ failure.
In critically ill patients the kidney is usually an innocent bystander whose function is
disturbed by the systemic effects of a disease process remote from the kidney. In general,
preservation of renal function is best achieved by restoring and maintaining normal organ
perfusion, avoiding nephrotoxic drugs and instituting effective treatment for the primary
disease process.
Renal replacement therapy is required when renal function has been
so badly affected that recovery will take several days or weeks and
the patient is at risk from the side effects of renal failure. The aim is
to provide a substitute for renal function to allow removal of the waste
products normally excreted by the kidney. There have been many
developments over the last twenty-five years that have simplified
renal replacement therapy for the ICU patient suffering from acute
renal failure.
It is essential that the intensivist has a clear understanding of the
pathophysiology of acute renal failure and the means by which it can
be treated or, more importantly, prevented.
Reference to the website of the Acute Dialysis Quality Initiative will
be of value to accompany this module, see reference below. This site
aims to distil the current evidence regarding the management of
patients at risk of or suffering from acute renal failure. There is a
constant increase in the data available at this site.
1/ HOW TO DIAGNOSE ACUTE RENAL FAILURE
Renal failure in the ICU is
usually secondary to other
pathology and not primary
renal disease
It is usually associated with
multiple insults, most often
hypovolaemia, hypotension
and nephrotoxic drugs
Rule out any cause outside
the kidney
What is the definition of renal failure?
The primary function of the kidney is to eliminate water-soluble waste products of metabolism and other po
(e.g. drugs).
Acute renal failure is the sudden (and usually reversible) failure of the kidneys to excrete nitrogenous and
causing loss of homeostasis and retention of these products within the body.
The investigation of acute renal failure in the critically ill has been hampered by the lack of consensus conc
the severity of renal impairment. Most studies have used different criteria, making comparisons of treatmen
difficult.
Chronic renal failure is the irreversible loss of, or reduction in, the capacity of the kidney to excrete nitrogen
products causing retention of these products within the body. This is due to a permanent loss of functioning
In some circumstances acute renal failure occurring in the ICU patient may rarely progress to severe or per
failure.
N OTE
There is a continuum of acute impairment of renal function from rapidly
reversible oligo-anuria to established acute renal failure. Early detection of
impending renal impairment and prompt correction of the cause or causes will
reduce the chance of the development of established acute renal failure.
See the PACT module on Oliguria and anuria
for more information on this
topic.
Clinical history
There are few symptoms of acute renal failure, particularly in the early
stages, but an accurate and comprehensive history is essential. In many
situations in the ICU the history will have to be gained from family and
friends, the patient's family doctor, or a comprehensive review of the
medical and nursing notes.
Specific information should be sought about:
 Symptoms suggestive of pre-existing renal disease, e.g.
nocturia, periods of total anuria, haematuria, renal colic
 Recent surgical procedures, trauma
 Recent episodes of hypotension, infection, coma or
prolonged immobility
 Past medical history e.g. obstructive uropathy, cardiac
disease, hypertension, peripheral vascular disease,
chronic renal impairment, diabetes mellitus, liver disease,
radiological contrast medium exposure, cancer treatment
or transplantation
A good history is vital for
patient management

Family history of renal disease (e.g. polycystic kidneys)

Prescribed medication :
o Antihypertensives e.g. angiotensin-converting
enzyme (ACE) inhibitors, β-blockers, diuretics
o Analgesics e.g. non-steroidal anti-inflammatory
drugs (NSAIDs), paracetamol (acetaminophen)
o Antibiotics
o Chemotherapy and immunosuppressives e.g.
ciclosporin, platinum compounds
Non-prescribed medication e.g. laxatives, recreational
drugs, herbal remedies, analgesics (particularly NSAIDs)

Confirm the importance of a
complete history, particularly
in relation to drug ingestion
In the next 10 cases you see of acute oliguria/renal failure assess the value and
relevance of obtaining a complete history.
Why might ACE inhibitors precipitate oliguria in the ICU patient ?
Physical examination
Physical examination is commonly unhelpful in providing evidence of acute renal failure but the presence o
water depletion, vasculitic lesions, hypersensitivity rash, enlarged kidneys or bladder should be sought.
Urinalysis must not be forgotten as this may provide valuable clues
as to the underlying cause of renal failure.
Always perform urinalysis
3/ HOW TO MANAGE THE PATIENT WITH ACUTE RENAL FAILURE
C OMMUNIC ATI ON
Intensive care units should develop protocols for the management of
oliguria/acute renal failure, including the role of the nephrology service.
Renal perfusion
From what has been discussed above, it should be obvious that restoration of optimal renal perfusion is the
most important step. This requires:





Correcting any deficit in the circulating volume
Ensuring that cardiac output is adequate for the individual
patient
Restoring perfusion pressure to a level that will allow
glomerular filtration in the presence of impaired
autoregulation. This will vary depending on the patients'
normal blood pressure.
Relieving abdominal tamponade
In rare cases restoring the patency of the aorta or renal
The first priority is to correct
circulatory deficits and restore
renal perfusion
arteries
These interventions must be carried out in the sequence described.
What might be the adverse effects of attempting to restore perfusion pressure with vasopressors
prior to the restoration of an adequate circulatory volume?
The selection of the most appropriate fluids, inotropes and vasopressors is discussed elsewhere, see the P
modules on Oliguria and anuria
, Hypotension
, Sepsis and MODS
and Heart failure
. The e
would suggest that dobutamine and norepinephrine, either alone or in combination depending on the haem
disturbance, are the agents of choice.
In many situations achieving these goals will result in the restoration of urine production by ensuring filtratio
face of impaired autoregulation.
A NECDOTE
An example of this effect is seen (figure below) in this young adult with
meningococcal sepsis whose mean arterial pressure, urinary output and
metabolic acidosis were not corrected by volume replacement and antibiotics
alone. Norepinephrine was commenced and titrated to increase the MAP. The
metabolic acidosis resolved and urinary output increased, with a fall in serum
creatinine.
Patency of lower urinary tract
Once circulatory abnormalities have been corrected the next step is
to ensure that there is no obstruction of the lower urinary tract (e.g.
bladder catheterisation, imaging of the lower urinary tract by
ultrasound or CT scan.)
C OMMUNIC ATI ON
Infection within an obstructed
urinary collecting system
needs urgent drainage
Percutaneous nephrostomy may be required in the presence of ureteric
obstruction. This can be performed in
the intensive care unit under ultrasound guidance by an interventional
radiologist.
Absolute anuria indicates an obstructed lower urinary tract until proven otherwise.
N OTE
The presence of infection within an obstructed collecting system requires
emergency relief of the obstruction in addition to antimicrobial treatment. This is
a surgical emergency and urological advice should be obtained without delay.
Without relief of the obstruction the kidney will be destroyed.
Relief of a chronically obstructed urinary tract may precipitate a massive diuresis. This is, in part, the result
osmotic diuresis as retained solute is cleared, but more importantly is a consequence of damage to the dist
nephron causing a salt and water losing state.
Haemofiltration process
This is a convective process in which a hydrostatic pressure gradient
is used to filter plasma water and solute across a membrane. This
fluid is then discarded. The properties of the membrane determine
the size and charge of the solute that can be removed and the rate at
which water will be filtered for any given driving pressure. This
process mimics the function of the glomerulus. Excess water and
essential solute that is lost in the filtrate must be replaced from a
sterile source of fluid.
Haemodialysis process
This is a diffusive process where blood is passed over a semipermeable membrane which separates it from an electrolyte solution
flowing in the opposite direction. The electrolyte solution contains
essential solute present in plasma water and waste solute is removed
by its movement down a concentration gradient from plasma water
into the electrolyte compartment (this fluid is commonly referred to as
dialysate).
Convection describes a
process by which solutes are
transported across a
semipermeable membrane
together with the solvent by
means of filtration driven by a
transmembrane pressure
gradient
Diffusion describes a process
of solute transport across a
semi-permeable membrane
driven by a concentration
gradient such that the solute
will tend to an equal
concentration in the available
distribution space on both
sides of the membrane
Diagram
representing
diffusion through
a semipermeable
membrane on
the left and
convection on
the right
Renal replacement systems may rely predominantly on haemofiltration (convection) or haemodialysis (diffu
there are also systems that combine the two methods.
Nomenclature of renal replacement therapy
There is a plethora of acronyms that have been generated to describe the various techniques that have be
employed to provide renal replacement therapy (RRT). A consensus statement has been produced for con
renal replacement therapy.
Renal replacement therapy may be Intermittent or Continuous and is described and differentiated by the pr
C respectively.
It must be remembered that true continuous treatment is an aspiration and that there are many reasons (p
and unplanned) why treatment may be interrupted for variable lengths of time in caring for the critically ill.
The type of extracorporeal circuit is then described e.g. arterio-venous AV and pumped veno-venous VV. T
followed by the method of blood purification e.g. haemofiltration H, haemodiafiltration HDF, haemodialysis
Therefore continuous veno venous haemodiafiltration would be represented by CVVHDF. Examples will be
later in this task. For more information about the nomenclature, see the following reference.
When to start RRT?
Absolute indications
 Uncontrollable hyperkalaemia.
Renal replacement therapy




Salt and water overload causing or exacerbating severe
pulmonary oedema, which is unresponsive to diuretics or
other measures.
Severe metabolic acidaemia in the face of acute renal
failure e.g. ethylene glycol or metformin toxicity.
Complications of a high blood urea (azotaemia) causing
symptoms of the clinical syndrome of uraemia such as
pericarditis, encephalopathy, neuromyopathy or bleeding
disorders.
Severe electrolytic disorders associated with renal failure
e.g. hypercalcaemia, severe hyponatraemia.
should be instituted on the
basis of both the individual
patient's disease process and
biochemical results


Removal of a dialysable toxin e.g. Lithium carbonate.
Raised blood urea (azotaemia). The absolute value of blood urea at which treatment should be
not universally agreed. The level of blood urea at which the symptoms of the uraemia syndrome
evident varies considerably between patients and the rate of rise of blood urea. A blood urea of
mmol/l in a patient with no evidence of recovering renal function despite standard treatment, as
described in Task 4, should receive prompt renal replacement therapy. Most would accept an u
of 30 mmol/l while receiving renal replacement therapy although many would prefer the limit to b
to 20 mmol/l.
In the situation of a critically ill patient with no evidence of recovery of Start renal replacement
renal function despite standard supportive measures following a
therapy early rather than late
major insult or sepsis, the threshold for renal replacement therapy is
much lower. The rise in urea will be rapid and it is probably unwise to
allow the urea to rise above 30 mmol/l before starting treatment.
Starvation or limitation of protein intake should not be used to delay
the need for renal replacement therapy. It is better to provide
appropriate nutritional intake and intervene with renal replacement
therapy early.
Do not starve patients in an
attempt to avoid renal
replacement therapy results
In what group of patients might you consider waiting longer before instituting renal replacement
therapy?
In the next 10 patients you see with a blood urea concentration greater than 30
mmol/l, record any features of the uraemia syndrome that are present. Try to
relate these to the rate of rise of the urea concentration.
Relative indications
Control of severe hyperthermia or hypothermia is a relative indication.
A relative indication for the institution of renal replacement therapy in the form of high volume haemofiltrati
been suggested to be the presence of severe sepsis. This treatment uses very large volume exchanges (o
order of 100 litres per day) and high permeability membranes. It has been found that inflammatory mediato
be removed by both filtration through and adsorption onto haemofilter membranes. It is postulated that rem
inflammatory mediators by this treatment may promote reversal of the haemodynamic and respiratory
consequences of severe sepsis. Evidence in humans to support this concept is at present not available an
are potential deleterious effects of the removal of beneficial inflammatory and counter-inflammatory mediat
the cut off limit for permeability rises to increase the removal of mediators there is an increasing loss of alb
which is undesirable.
There are also potential problems with high volume changes over short periods of time and the systems us
have very accurate volume measurement and control with very low tolerance limits.
The simplistic view that isovolaemic high volume exchange will not result in significant net solute change h
challenged by the findings of significant net changes in small molecular weight solute over the course of la
volume exchange treatment with no net volume change. The net change in solute transfer was dependent
proportion of replacement fluid returned pre filtration or post filtration.
There are major logistical problems of handling and storing such large volumes of replacement fluid if onlin
production of fluid is not available.
What methods are available?
Peritoneal dialysis
This technique uses the peritoneal lining as a semi-permeable membrane to allow equilibration of solute w
dialysate introduced into the peritoneal cavity, the volume of dialysate used being dependent upon the pati
(normally 2 litres in an average adult). This fluid is left in the peritoneal cavity for a period of time ('dwell tim
drained and replaced by fresh dialysate. Good clearance of solute can be obtained by this method but it su
from a number of disadvantages, particularly in the critically ill patient and currently is seldom used in the a
The technique is used more commonly in paediatric practice. One potential advantage is that peritoneal dia
does not require the use of anticoagulants.
Complications of peritoneal dialysis.
Technical



Clinical
Perforation of viscus
Perforation of blood vessel
Failure to enter peritoneal cavity





Peritonitis
Diaphragmatic splinting/ increase in intra-abdominal pressure
Hydrothorax
Electrolyte disturbance
Hyperglycaemia
What advantages or indications can you list for peritoneal dialysis?
Haemodialysis
Haemodialysis is the traditional method of acute and chronic renal replacement therapy introduced into clin
practice by Kolff. Blood is passed, via an extracorporeal circuit, through a haemodialyser containing a sem
permeable membrane. This allows adequate exchange of small molecular weight solutes into the dialysate
hence their removal from the body. The efficiency of the process is affected by several factors :




Rate of blood flow through the haemodialyser
Membrane properties (high or low flux)
Rate of flow of dialysate
Membrane surface area
Size dependent free diffusion coefficients of solutes in water
and various membranes
Relationship of movement of
solute by diffusion according
to molecular weight (x-axis)
and membrane permeability
(y-axis). The diffusion coefficient is inversely related to
the molecular weight of a
molecule.
The three coloured lines
represent this relationship as
it applies in water at 37° C
and membranes of different
permeability (flux). Reference
molecules are shown at their
respective molecular weight.
High flux haemodialysis
In this technique high flux dialysers are utilised in a continuous haemodialysis circuit with continuous ultraf
volume control. Since the spontaneous filtration occurring in the hollow fibre dialyser would be much great
the desired fluid loss, a positive pressure is automatically applied to the dialysate compartment and the
transmembrane pressure gradient is reduced significantly. This in turn results in a very special pressure pr
inside the dialyser. Large amounts of filtration and consequently of convective transport are maintained in
proximal part of the haemodialyser in spite of a moderate net filtration. The net fluid balance is obtained tha
significant amount of backfiltration of fresh dialysate in the distal portion of the dialyser. In this mechanism
and convection are conveniently combined. A modification of this technique is continuous high flux dialysis
continuous treatment is used rather than the more common intermittent form.
In general, haemodialysis is effective for the removal of small molecular weight solutes and becomes incre
less efficient as molecular weight rises above a thousand daltons (see diagram).
A=artery / V=vein / P=pump / Di=dialysate in / Do=dialysate out / Qb=blood flow
Qf=ultrafiltration rate / Qd=dialysate flow / h=heparin
Schematics
describing
continuous
haemodialysis
driven by
arterio-venous
AV, pumped
Veno-venous
VV and
continuous VV
high flux
dialysis
Representative
values for blood
flow, filtration
rate and
dialysate flow
are given
Clearance of solute is most rapid at the institution of treatment when the concentration gradient for solute i
highest. Anticoagulation of the circuit is required.
Haemofiltration
Haemofiltration has found most favour in European and Australasian intensive care practice over the past
Blood is circulated through an extracorporeal circuit and a haemofilter. The rate of fluid removal is determin




Rate of blood flow
Hydraulic conductance (permeability) of the membrane
Hydrostatic pressure gradient across the membrane
Surface area of the haemofilter membrane
Ultrafiltration (UF)
rate versus TMP
impact of
membrane
permeability
Effect of membrane
composition on
permeability and
ultrafiltration rate.
For a given
transmembrane
pressure (TMP) the
higher the
membrane
permeability (Kf)
the more fluid is
filtered per unit time
Replacement fluid is returned to the circuit either before (pre dilution) or after the haemofilter (post dilution)
that will maintain the desired overall fluid balance.
Pre dilution reduces the risk of clotting in the filter by reducing the
haematocrit but diminishes the clearance of urea and creatinine by
diminishing the concentration of both compounds in the filtered
volume.
The amount of solute clearance per unit time is dependent on the
volume of fluid exchanged in that time.
According to the construction of the membrane, solute of high (up to
50 000 daltons) molecular weight can be filtered. There are reports of
this being of benefit in the critically ill.
Anticoagulation of the circuit is required.
There is no current
information on the
clearance of drugs during
high volume
haemofiltration at the
current suggested levels of
35 ml/kg/hr
Schematic of
continuous
haemofiltration driven
by arterio-venous
(CAVH) or veno-venous
(CVVH) circuits
In the examples
replacement fluid is
given after the filter i.e.
post dilution
A=artery / V=vein / P=pump / Uf=ultrafiltrate / Ufc=ultrafiltration controller
R=replacement fluid / Qb=blood flow / Qf=ultrafiltration rate / h=heparin
Haemodiafiltration
This process combines the two processes of diffusion and convection by introducing a countercurrent flow
dialysate into the non-blood containing compartment of the haemodiafilter. This increases the efficiency of
clearance of small molecular weight solute over that of standard haemofiltration. This technique was origin
introduced to increase the limited clearance of urea and other small molecular weight solute in non-pumpe
venous haemofiltration systems dependent on the patient's own circulation.
Anticoagulation of the circuit is required.
Schematic of arteriovenous and venovenous
haemodiafiltration
(CAVHDF and
CVVHDF) and the
typical operational
parameters used for
these techniques
A=artery / V=vein / P=pump / R=replacement fluid / Di=dialysate in / Do=dialysate out
Qb=blood flow / Qf=ultrafiltration rate / Qd=dialysate flow / h=heparin
Requirements for RRT
Extracorporeal circuit
For all methods requiring an extracorporeal circuit, the current preferred system is to have a pump driven b
circuit with vascular access established by the insertion of a large double lumen venous catheter, a veno-v
circuit. These circuits are now components of increasingly sophisticated machines that control blood flow,
ultrafiltration rate and the rate of fluid replacement during haemofiltration. These machines allow the runnin
circuit with appropriate safety systems and precise control of volume removal and replacement, thereby m
the risk of the major volume errors which could occur with the older more primitive systems. They also help
control the temperature of the fluid returning to the patient and thus limit the development of hypothermia.
The Prisma, the
Equasmart and the
Aquarius machines
The easy interface
makes them suitable for
most of the CRRT
techniques available at
present
The Prisma, The Equasmart, The Aquarius
The older arterio-venous circuits, which required vascular access via
a formal Scribner shunt or large percutaneous catheters inserted into
both the femoral artery and vein, are now seldom used. It is now
unusual for the extracorporeal circuit to be driven by the patient's
circulation. The establishment of satisfactory vascular access is
essential for the efficient functioning of all of the extracorporeal
systems. Poor vascular access and low blood flow are the most
common causes of circuit clotting.
Passive, patient driven
extracorporeal circuits are
generally unsatisfactory and
now rarely used
Example of a typical patient
driven CAVH
extracorporeal circuit
There is a risk of infection as is the case for any central venous indwelling catheter.
Attempts have been made to define an appropriate policy for catheter replacement.
A recent report has suggested that catheter replacement on the basis of clinical indication allows for signifi
fewer catheter insertions over the course of an individual's acute RRT course, without any increase in cath
sepsis rate.
Why are patient driven, non-pumped systems no longer favoured?
Anticoagulation
The extracorporeal circuit will normally require anticoagulation (in the critically ill the associated coagulopa
allow the circuit to run without anticoagulant). Traditionally this has been achieved using unfractionated he
tight control of APPT or ACT as there is a significant risk of bleeding (10%). In situations of high bleeding r
heparin-induced thrombocytopenia (HIT), heparinoids, prostacyclin or sodium citrate may be used. Further
experience is being gained with the use of low molecular weight heparin and hirudin and argatroban.
In the next 10 cases you see of extracorporeal circuit clotting in patients
receiving haemofiltration, list the potential causes and the measures taken to
reduce the risk of further clotting.
Buffering agents
For chronic haemodialysis the traditional buffer in dialysate fluid was
acetate which was metabolised to bicarbonate. Acetate has been
shown to cause vasodilatation and should be avoided in the critically
ill. The most common buffer currently used is lactate, which is
converted in muscle and the liver to bicarbonate. Lactate is suitable
for all patients other than those with established impaired hepatic
function or with severe sepsis where lactate metabolism is
significantly impaired. The buffer of choice is bicarbonate but the
ability to produce on line replacement fluid is still limited. New
commercially available replacement fluid preparations containing
bicarbonate have recently appeared on the market. The two major
electrolytes that are not present in these fluids are potassium and
phosphate. Potassium may be added according to the patient's
current blood level but phosphate is incompatible with the solution.
Serum phosphate may become significantly reduced with large
volume haemofiltration or intensive dialysis and usually requires
separate replacement. When sodium citrate is used as the
The ideal buffer for renal
replacement therapy in the
critically ill is bicarbonate
Phosphate depletion is a
common complication of
continuous renal replacement
therapy
anticoagulant no added buffer is required as citrate is converted into
bicarbonate by the patient. Specially designed replacement fluid is
available with no buffer and a low sodium to compensate for the large
sodium load administered as sodium citrate.
Why is bicarbonate so difficult to use as the buffer in dialysate/replacement fluid?
What are the potential adverse effects of a low serum phosphate?
For more information on hypophosphataemia see the following reference.
Which method for critically ill patients?
Attempts have been made to demonstrate the superiority of
haemofiltration over haemodialysis in several studies. It is extremely
difficult to conduct randomised controlled trials in a heterogeneous
patient population as the methods for controlling for all the potential
variables are probably still not sufficiently sophisticated.
As yet the ideal RRT regimen
for the treatment of acute
renal failure in the critically ill
is not established
There is as yet no clear-cut evidence of superiority of one process over the other in the critically ill.
Uncertainty also remains regarding the place of continuous versus intermittent treatment in the critically
ill. Homeostasis is better maintained by continuous treatment with apparent improved haemodynamic
stability but at the risk of the complications of long term anticoagulant exposure.
Avoid intermittent therapy and
rapid solute removal in
conditions associated with
cerebral oedema
In situations where there is haemodynamic instability or cerebral oedema
continuous treatment is preferred to minimise sudden osmotic shifts of body
water. It is also important to avoid major cardiovascular instability, which can be
caused by short duration, high efficiency intermittent treatment as it is felt that
this will delay renal recovery in the presence of impaired autoregulation.
Modern management in the ICU is normally achieved using a pumped system to achieve adequate
blood flow and therefore allows a sufficient daily exchange volume during
haemofiltration/haemodiafiltration to maintain satisfactory levels of urea and creatinine. As patients
recover there is scope to use the most convenient method that allows proper rehabilitation. The
technique of providing renal replacement therapy should be tailored to the clinical situation and may
change from continuous to intermittent and from predominantly convective to diffusive. Any method
used must be performed by a team skilled in its use.
What are the potential disadvantages of continuous renal replacement therapy?
Does the filtration/dialysis membrane play a part in patient outcome?
Older membrane materials such as the cellophane-based membranes (Cuprophan) have been shown
to activate the complement system. It has been proposed that the newer membranes such as those
based on polyacrylonitrile (PAN), polysulphone and polycarbonate confer a survival advantage when
used in the critically ill compared with cellophane based membranes. Studies have been published
which both support and refute this hypothesis.
The newer artificial membranes allow easier passage of higher molecular weight solutes ('middle
molecules') which seem to play an important role in the toxicity of uraemia. They also allow for a higher
hydraulic conductance and high filtration rates and are generally preferred for haemofiltration in the
critically ill. High volume (approx 6 l/hr exchange) requires the use of high hydraulic conductance
membranes.
What level of blood urea and creatinine?
There is no clear evidence from the literature that maintaining urea
and creatinine levels lower than 30 mmol/l for intermittent treatment
or less than 20 mmol/l for continuous treatment results in a better
patient outcome.
Others have claimed that the urea clearance in relation to the time of
treatment and volume of distribution (Kt/V) should be estimated and
that this value correlates with mortality rate. However this has not as
yet been confirmed.
Conversion factors from SI to
conventional units:
Creatinine x 0.0113 mg/dL
Urea x 2.8 mg/dL
Similarly it has been suggested that haemofiltration with a higher daily exchange volume and therefore
a lower average level of circulating solute waste improved patient outcome. The results of the trial by
Ronco et al can be found in the reference below.
In a study of early high volume (72-96 l/day) versus early and late low volume (24-36 l/day) however no
difference was found in outcome (survival and recovery of function).
The Acute Dialysis Quality Initiative has been set up to try to establish the appropriate level of renal
replacement therapy that will result in the best patient outcomes. This may be visited at the following
website.
How long should RRT be continued?
As the renal
tubular cells
regenerate
and reestablish a
normal tubular
membrane,
glomerular
filtration will
re-commence
and urine
output will
increase.
Once
clearance of
solute waste
is sufficient to
maintain urea
at less than
30 mmol/l,
treatment can
be
discontinued,
remembering
that care must
be taken to
avoid further
insults (e.g.
hypotension
or
hypovolaemia)
to the kidneys
as they
recover and
regain their
normal
intrarenal
compensatory
capacity. In
the elderly
critically ill
patient
recovery may
take up to
three months
and on
occasions
even longer.
What complications can occur during haemofiltration/haemodialysis?
Vascular access
 Vascular damage causing occlusion or haemorrhage
 Infection
 Insertion complications e.g. pneumothorax

Renal replacement therapy is
not without risk and must be
carried out and supervised by
trained personnel
Process
o
o
o
Dysequilibration (more common with short duration intermittent haemodialysis)
Hypotension
 ECF loss through membrane/by accident or design
 Hypersensitivity to membrane
 Acetate buffer
 Pyrogens
Haemorrhage
 Circuit disconnection
 Anticoagulation
o
o
o
Haemolysis
Electrolyte disturbance
Air embolism
CONCLUSION
The outcome for recovery of renal function is good in the vast
majority of the critically ill with previously normal renal function. By six
months they will normally have recovered greater than 90% of their
pre insult function. There is a small but significant incidence of nonrecovery of function such that chronic renal replacement therapy is
needed. This is most common in the elderly, and those with a
vasculitis or pre-existing renal disease. Cortical necrosis in adults
secondary to obstetric disaster is now a very rare event in western
medicine.
The direct effect of acute
renal failure on survival in the
critically ill is still not entirely
clear
Survival of critically ill patients with acute renal failure is highly dependent upon the cause of the underlying
disease and other comorbidities. The mortality for those presenting to the intensive care unit with establish
renal failure requiring renal replacement therapy is better than for those who develop acute renal failure at
date despite critical care management. This latter group is usually those who have progressive multiple org
failure with its known poor outcome.
With modern forms of renal support, death from renal failure alone should not occur. Survival rates for acu
failure are generally reported to be around 40-50%. As multi organ failure involves more organ systems mo
rate steadily increases. It has been suggested using observational data that acute renal failure per se has
on mortality. However as acute renal failure is not a specific disease process rather a syndrome secondary
disease states it is difficult to separate the effects of the primary disease process, the length of time of the
prior to initiation of appropriate treatment (e.g. restoration of adequate tissue perfusion) and the individual
response to the primary disease from the effect of the acute renal failure. Although scoring systems are inc
in sophistication it is debateable whether they have achieved the discrimination necessary to resolve this is
PATIENT CHALLENGES
A 72-year-old woman, Mrs A, is admitted to your hospital as an emergency with a two day history of abdo
pain of sudden onset. She has a history of hypertension and angina treated with enalapril, diuretics and a β
Her exercise tolerance is normally good. Her admission pulse rate was 124 beats/min, BP 110/65 mmHg.
noted to have peritonism and there was free gas under the diaphragm. She was taken for laparotomy after
resuscitation. Preoperatively her urea was 15 mmol/l and creatinine 195 mmol/l. Arterial blood gases show
oxygenation but a pCO2 of 4.1 kPa, pH of 7.29 and BE of −9 mmol/l. At operation gross faecal peritonitis w
discovered secondary to perforation of the sigmoid colon which was severely affected by diverticular disea
Hartmann's procedure (resection of diseased colon, end colostomy and closure of rectal stump) was perfo
Learning
issues
Clinical history
Postoperatively she was cold but her BP was 175/80 and her urine output was 75 ml/hr. Three hours later
asked to see her in the recovery room with a view to ICU admission. She is intubated and being ventilated.
pulse rate is 140/min, sinus rhythm, BP 100/60 mmHg, CVP +6 mmHg, core temperature 37.7 °C with mar
vasodilatation. Urinary output has been 40 ml over the past three hours. Arterial blood gases pO 2 9.6 kPa,
pCO2 6.2 kPa, pH 7.15, BE −12 mmol/l. She is receiving tazobactam as broad spectrum antibiotic cover an
morphine as an analgesic.
What are the initial management imperatives to restore urinary output?
Learning issues
Restoration of the circulation
What are your goals for blood pressure and cardiac output and why?
N OTE
In the previously
hypertensive patient a
higher mean arterial
pressure (MAP) may be
necessary for adequate
organ perfusion
Learning issues
PACT module on Hypertension
Mrs A responds well to fluids and a vasopressor. Her MAP rises to 90 with normalisation of her ST segmen
improvement in her urinary output and correction of her metabolic acidosis. She requires a considerable vo
fluid over the next two days as her abdomen distends. On the third day her gas exchange deteriorates and
an increase in cardiac output her perfusion pressure falls, requiring an increase in the norepinephrine supp
Renal function deteriorates with worsening oliguria despite restoring the circulation. On examination the co
was ischaemic. Mrs A was taken for exploration of her colostomy, which was found to be devascularised to
proximal to the skin margin. The ischaemic section of bowel was removed and a new colostomy refashione
the next few hours Mrs A's urinary output improves and her renal function recovers.
Learning issues
Metabolic acidosis
PACT module on Homeostasis
Secondary versus primary renal insult
Oliguria
PACT module on Oliguria & anuria
Underlying causes
A visiting trainee asks why dopamine was not chosen in a renal dose as he has witnessed in
other hospitals. What is your reaction?
Learning issues
Specific treatments
Mrs A develops a Methicillin Resistant Staphylococcus aureus (MRSA) infection of her abdominal wound a
respiratory tract. She is treated with teicoplanin and rifampicin. At day 12 as she is recovering from her res
failure and is being weaned from her vasoactive drugs Mrs A develops a fever 39.6 °C, a florid maculapap
neutropenia and diminishing renal function with a rising urea and creatinine.
Rash developing 9 days after commencement of antibiotics
Learning issues
PACT module on Severe infection
What should be the response to Mrs A's further deterioration in renal function?
Learning issues
Renal perfusion
Causes of acute renal failure
Renal replacement therapy
Mrs A is found to have no circulatory deficit or urinary tract obstruction. No new infectious or other occult
pathological processes are discovered. Ultrasound shows enlarged echogenic kidneys consistent with acu
failure. Urinalysis showed 2+ proteinuria.
Learning issues
Imaging
PACT module on Clinical imaging
What is the likely cause of the renal dysfunction?
Learning issues
Interstitial nephritis (1)
Interstitial nephritis (2)
Renal biopsy
Multiprofessional collaboration (1)
Multiprofessional collaboration (2)
Multiprofessional collaboration (3)
Multiprofessional collaboration (4)
How would you treat the presumed interstitial nephritis and would you do so without
having performed a renal biopsy?
Explain your answer.
N OTE
Do not feel
compelled
to initiate
unproven
treatments
because
there is no
other
specific
therapy
available
Do no
further
harm!
In Mrs A's case, the risks of steroid treatment are felt to far outweigh the unproven benefits and therefore w
Mrs A's renal function deteriorates such that she requires renal replacement therapy (RRT) despite prompt
discontinuation of her antibiotics. She becomes very drowsy and then unresponsive with small pupils. She
by haemofiltration and her renal function recovers to a point that she no longer requires RRT after 10 days
Learning issues
Renal replacement therapy
Haemofiltration
Why might Mrs A have become so drowsy and what should be done?
Learning
issues
Opiate toxicity
Mrs A gradually recovers normal consciousness over four days and is extubated a week after starting rena
replacement therapy.
She asks if she will require kidney treatment permanently. What do you tell her?
Learning
issues
Outcome
Now that Mrs A no longer requires renal replacement therapy, why does she require continued
detailed attention to her renal function?
N OTE
Remember that the kidney's ability to maintain fine control of electrolyte and water
balance will take some weeks to recover
Mrs A recovers from her septic state and her drug induced interstitial nephritis. She is discharged home fiv
after her emergency surgery, with a creatinine of 125 mmol/l. Her creatinine had returned to 80 mmol/l whe
at the follow-up clinic six months later.
A 25-year-old man, Mr B, is admitted to hospital unconscious. He had started working on his car with
engine running in a closed garage. He had taken the precaution of leaving only a small quantity of fuel in th
and the engine had stopped by the time he was found several hours later.
On admission he was hypothermic (34.5 °C), shocked PR 140/min, BP 80/50 with a severe metabolic acid
(BE −20) and carboxyhaemoglobin level of 35%. The serum creatinine was 256 µmol/l and urea 9 mmol/l.
were red marks over his left shoulder, lower leg and buttock corresponding to the position in which he had
found lying on the floor.
Learning issues
PACT module on Homeostasis
On arrival he was intubated and ventilated with 100% oxygen and resuscitated with intravenous fluid which
his blood pressure to 110/70 mmHg. His CVP continued to fall after each fluid challenge. As his perfusion
the urine obtained via the urinary catheter was noticed to be brown (see image below), contained obvious
and was strongly positive for haem on dipstick testing. Microscopy revealed no red cells in the spun sedim
Learning issues
Intubation
PACT module on Airway management
Renal perfusion
Microscopy
PACT module on Oliguria & anuria
What is the likely cause of the urine changes and the high creatinine?
The history of
unconsciousness with the
presence of pressure marks
should cause immediate
suspicion of rhabdomyolysis
What confirmatory investigations are appropriate?
Why is this young man requiring such large volumes of fluid to maintain his circulating volume?
N OTE
The major threat to renal function in rhabdomyolysis is the severe extracellular fluid
depletion combined with the toxic effects of the products of muscle breakdown
The SCPK of Mr B is found to be very high at 124 000 iu/l confirming the diagnosis of rhabdomyolysis. By
the left buttock and shoulder have begun to swell very obviously.
Severe swelling of the buttock following pressure induced muscle necrosis
Learning
issues
Rhabdomyolysis
N OTE
If you suspect rhabdomyolysis you must act quickly
What measures must be taken to prevent the development of established acute renal
failure ?
N OTE
N OTE
Circulation,
Circulation,
Circulation
Multiprofessional collaboration
Mr B's circulation is maintained as his muscles swell. He requires a positive fluid balance of 12 litres over t
36 hours. His urine is alkalinised using isotonic sodium bicarbonate infusion as part of his resuscitation flui
carboxyhaemoglobin rapidly falls and his conscious level improves. The surgical team assesses his muscl
and he is taken for fasciotomy of his lower leg compartments. No muscle resection is required. His urinary
established at greater than 100 ml/hr and his creatinine peaks at 48 hours at a level of 358 µmol/l before re
to normal. He makes a good functional recovery.
What complications of rhabdomyolysis would be likely to develop in this patient in the short
term?
Learning issues
Treating complications
PACT module on Homeostasis
Mr C, aged 68, is brought to the emergency department unconscious, hypotensive and in respiratory
His arterial blood gases on admission show PaO2 7.9 kPa on an FiO2 1.0, PaCO25.2 kPa, pH 7.01 and BE
mmol/l. His potassium is 9.8 mmol/l. His ECG is as shown (classic hyperkalaemia with bradycardia, absen
wave and QRS almost a sign wave). You have been called to see him to assist and just as you arrive he v
aspirates and has a respiratory arrest.
Learning issues
ECG changes of hyperkalaemia
Management of acute hyperkalaemia
What are your priorities?
N OTE
Ensure adequate oxygenation and hyperventilation in the presence of a severe metabolic
acidaemia
Learning issues
Treatment of hyperkalaemia
As his resuscitation is proceeding more history is obtained. Mr C has been having nocturia 3-4 times per n
is due to see the urologists. He has been taking diclofenac for bone pain for the last three months. This ha
thought to be due to an osteoid osteoma, which was to be dealt with by the orthopaedic surgical service ne
month. Just then his urea is reported to be 96 mmol/l and his creatinine 1783 µmol/l. Blood sugar is norma
lactate is 2.5 mmol/l.
What other features of the physical examination might you concentrate upon in view of this
information?
Learning issues
Lower urinary tract patency (1)
Lower urinary tract patency (2)
What procedure will you do next?
What are the possible reasons for Mr C's uraemia and metabolic upset?
Learning issues
Obstructive uropathy (1)
Obstructive uropathy (2)
Obstructive uropathy (3)
Actions of common nephrotoxic drugs
Mr C is catheterised successfully and 1800 ml of urine is obtained. By this time he is being ventilated (MV
with adequate oxygenation on a high FiO2. His circulation has improved after the administration of 3 litres o
partial correction of his hyperkalaemia to 6.6 mmol/l and support from dobutamine and norepinephrine. His
circulation is being monitored with the aid of a pulmonary artery catheter. Broad-spectrum antibiotics have
given. Urinary output is 150 ml in the past hour. He is transferred to the ICU.
How would you begin to manage his renal failure? Would you institute immediate renal
replacement therapy? Why?
Learning issues
Indications for instituting renal replacement therapy
Correction of metabolic acidaemia
N OTE
Correct the metabolic acidaemia gradually, as in obstructive uropathy the kidney cannot
eliminate non-volatile hydrogen ions
Mr C increases his urine volume over the next two hours to 350 ml/hr and his urea and creatinine begin to
requires a positive balance of six litres over the next 48 hours and his urea and creatinine steadily fall. His
acidaemia is corrected over the next 48 hours. E. coli is grown from his urine and blood. He steadily impro
his respiratory failure corrects over the next 15 days. He is eventually discharged from hospital with an ind
catheter, to return for prostatic resection once he has recovered his muscle mass. Investigation of his lowe
tract showed dilation of the ureters and hydronephrosis. His creatinine has stabilised at 215 µmol/l and ure
mmol/l.
What do you think the likelihood is that Mr C's renal function will return to normal with time?
Learning issues
Long term effects of obstructive uropathy (1)
Long term effects of obstructive uropathy (2)
Mr C's creatinine never fell below 210 mmol/l over the next three years.
On reflection, you have been presented with three challenging cases of critically ill patients with acute ren
In each patient the cause was a pathological process outside the kidney, rather than primary renal disease
usually the case in clinical practice). These cases emphasise that the aetiology of acute renal failure in crit
patients is frequently multifactorial, that the cause may not be immediately obvious, that treatment decision
complex and that collaboration with a nephrologist is therefore essential.
Thinking about the management of these three patients, what are the key messages you
have learned about how best to preserve or restore renal function? Q1. 'Renal dose'
dopamine has been shown in large RCTs to
Your answers
A. Reduce the risk of the development of acute renal failure in critically ill patients
The correct answer is :
False
B. Reduce the requirement for dialysis treatment in the critically ill with acute renal
impairment
The correct answer is :
False
C. Increase urine volume and sodium excretion (produce a diuresis)
The correct answer is :
True
D. Have significant cardiovascular effects
The correct answer is :
True
Low dose dopamine has been shown to increase cardiac output in critically ill patients with acute renal failure.
E. Be less efficient in protecting against radiocontrast induced acute renal injury in the
diabetic patient than salt loading
The correct answer is :
True
Studies have shown that administration of dopamine to diabetics as prophylaxis against radiocontrast induced
renal impairment produced a higher incidence of renal dysfunction than patients who were saline loaded.
Your total score is 0/5
Q2. A previously hypertensive patient is admitted to the ICU after an
emergency laparotomy, colonic resection and defunctioning colostomy,
following an anastomotic leak after an anterior resection for carcinoma of
the upper rectum. Initially he was hypertensive, hypothermic and
peripherally shutdown in the recovery room. Now he has become vasodilated
with BP 95/39 mmHg, heart rate 140 b/min, CI 3.4 l/m2, PCWP +4 mmHg,
SVR 400 dynes/cm/sec -5, oliguria and Base Excess of -9 mmol/l, Hb
14g/dl, pO2 9.5 kPa, pCO2 5.1 kPa. He has just arrived and is being
ventilated in the ICU. The following actions would be appropriate to restore
his renal function. Put also them in order of implementation.
Your answers
A. Administration of a vasopressor agent e.g. norepinephrine
The correct answer is :
True
In view of the low systemic vascular resistance and low blood pressure in a previously hypertensive individual,
raising the renal perfusion pressure would be appropriate ZiBaliseOuvrantehiZiBaliseFermantebut only after
correcting the circulating volume deficit suggested by the low PCWP.ZiBaliseOuvrante/hiZiBaliseFermante
B. Mannitol
The correct answer is : False - Mannitol might transiently increase the circulating volume but
is likely to cause an osmotic diuresis thus making the circulating volume deficit worse.
Mannitol has never been convincingly shown to prevent acute renal failure and has
produced acute renal failure when given in high dose.
C. Frusemide
The correct answer is :
False
Frusemide might cause a transient diuresis but will make any hypovolaemia worse. It will not improve renal
function.
D. Circulating volume expansion with appropriate fluid
The correct answer is : True - This is the first action that should be taken. The haemodynamic
data suggest a circulating volume deficit which is due to systemic vasodilatation secondary
to the septic insult and the sequestration of fluid into the bowel and peritoneal cavity,
combined with a generalised increase in microvascular permeability.
E. Administration of a β-adrenergic agonist e.g. dobutamine
The correct answer is : True - Administration of dobutamine as a β-agonist might be
appropriate if this patient†™s cardiac index did not improve with restoration of an
appropriate circulating volume. Care would be required as the vasodilating effects of these
agents may cause a further drop in perfusion pressure despite increasing cardiac output.
Your total score is 0/5
Q3. In obstructive uropathy
Your answers
A. Patients are normally fluid overloaded
The correct answer is : False - The effect of obstruction upon the distal nephron causes a
water and salt losing defect. Most patients with obstruction are therefore salt depleted.
B. Ultrasound will always demonstrate a dilated collecting system
The correct answer is : False - In a small proportion of patients in the very early stages of
obstruction it may be too early to demonstrate urinary tract dilatation.
C. Infection behind the obstruction can be safely left for several days without drainage,
provided antibiotics are given
The correct answer is : False - This is a true urological emergency and drainage of the
obstructed system must be performed as soon as it is demonstrated.
D. Absolute anuria makes this the presumptive diagnosis
The correct answer is : True
E. Bilateral ureteric obstruction is most commonly and easily relieved by retrograde
placement of ureteric stents via a cystoscope
The correct answer is : False - Percutaneous nephrostomy is the most convenient way of
dealing with the obstructed upper collecting system.
Your total score is 0/5
Q4. Renal replacement therapy
Your answers
A. Must always be started when the blood urea exceeds 30 mmol/l
The correct answer is : False - Treatment must be tailored to the individual patient.
B. Haemodialysis is more efficient at removing potassium than haemofiltration
The correct answer is : True
C. There is no place for peritoneal dialysis in critically ill patients
The correct answer is : False
D. High volume haemofiltration has been proven to improve survival of patients suffering
from severe sepsis in the absence of acute renal failure
The correct answer is : False - While inflammatory mediators may be removed and there is
some animal work suggesting benefit, there is as yet no convincing human data to support
this contention.
E. Is more efficient when driven by the patient's own circulation
The correct answer is : False - Pump driven systems are generally more efficient.
Your total score is 0/5
Q5. Acute renal failure in the intensive care unit
Your answers
A. Cannot be present if the patient is passing more than 50 ml of urine per hour
The correct answer is : False - It depends on solute clearance not simply urine volume.
B. Has a high mortality if present as a single organ failure
The correct answer is : False - Mortality is very low.
C. Is not normally caused by primary renal disease
The correct answer is : True
D. Can be caused by interstitial nephritis
The correct answer is : True
E. Is often associated with cortical necrosis
The correct answer is : False
Your total score is 0/5