Acute renal failure

The management of
acute renal failure

two separate criteria, the calculated GFR and urine output; it is

covered in more detail elsewhere in this issue (pages 42933).5
Although the RIFLE criteria may help in terms of defining ARF,
practical problems remain with this definition, including the
proposed calculation of the baseline creatinine as well as the
lack of consensus regarding initiation of treatment.

Andrew Slack
Serene Ho
Lui G Forni

At-risk populations
The two main in-hospital patient groups at increased risk of
ARF are those with pre-existing renal impairment and associated
co-morbidities, and those at risk of iatrogenic ARF. The first group
includes elderly patients and those with underlying chronic renal
impairment of any cause. Co-morbidities such as congestive
cardiac failure and hepatic disease add to the increased risk of
ARF following relatively mild insults. Those at risk of iatrogenic
ARF include patients undergoing major surgery or radiological
procedures involving intravenous contrast agents. Practically, in
the hospital environment there is considerable overlap between
the two groups.

Abstract
Acute renal failure is a commonly encountered condition in the hospital
setting. In many cases accurate history-taking, careful examination of the
patient and meticulous monitoring of volume balance may reverse this
process. However, acute renal failure presents a unique set of metabolic
derangements which, if untreated, will result in death. We outline the
initial management of acute renal failure as well as the specific treatments that may be required. Some consideration is also given to the use
of renal replacement therapies.

Prevention of ARF

Keywords acute renal failure; glomerular filtration rate; haemofiltration;

Simple measures may prevent ARF. These include the temporary

omission of nephrotoxic drugs together with appropriate adjustment of drug doses for the estimated GFR. Pre-operative optimization of a patients medical conditions should take place prior to
elective surgery and attention paid to adequate volume replacement before, during and after surgery. Wherever possible during
radiological investigation, non-ionic contrast agents should be
used in patients at risk of ARF with adequate hydration prior to
the procedure which may minimize the risk of contrast nephro
pathy. N-acetyl cysteine (NAC) has been proposed as a means
by which the risk of contrast nephropathy may be reduced but
its value in the prevention of contrast-induced nephropathy is
debatable.6

hyperkalaemia; metabolic acidosis; uraemic encephalopathy; uraemic

pericarditis

Acute renal failure (ARF) is a loss of glomerular filtration rate

(GFR) occurring over days or weeks, resulting in a loss of the ability to excrete soluble nitrogenous waste appropriately, together
with impaired fluid and electrolyte homeostasis.1 The incidence
of ARF is increasing, particularly in the elderly, although reporting suffers from the lack of consensus regarding a precise definition. UK-based population studies have estimated the annual
incidence of ARF from 486620 per million population, accounting for about 1% of hospital admissions and complicating more
than 7% of hospital inpatient admissions.2,3 ARF is a common
finding on the critical care unit with as many as 35% of patients
admitted to ICU requiring renal replacement therapy (RRT) and,
when present as part of multiple organ failure, mortality is over
90% if four organs or more fail.4 More than 30 definitions of ARF
are found within the literature prompting a recent collaboration
between nephrologists and intensivists to decide on a uniform
means of classifying ARF. This Acute Dialysis Quality Initiative
group (ADQI) proposed the RIFLE classification encompassing

Management of ARF
General management
Early recognition and treatment of ARF saves nephrons and
prevents further decline in the GFR. Importantly, the measured
serum creatinine may not actually rise appreciably until GFR
has fallen significantly. This is of particular relevance in individuals of small build, vegetarians and the undernourished
where a value in the normal range can be misleading. The
mainstay of treatment in ARF is aimed at minimizing damage
to surviving nephrons whilst providing support until the kidney
recovers. This includes restoration of the circulating volume,
relief of outflow obstruction if present, removal of tubular toxins
and specific treatment of glomerular disease. Early restoration of renal perfusion in precipitant ARF due to acute tubular
necrosis is essential. Recovery of GFR depends on the number
of remaining functional nephrons, which increase their filtration
to maintain GFR. However, continued hyperfiltration may lead
to progressive glomerular sclerosis and nephron death leading to
end-stage renal failure.
As there is no specific therapy for ARF, management should be
focused on addressing the causes as well as correcting metabolic

Andrew Slack MBBS BSc MRCP is a Specialist Registrar in Renal and

Intensive Care Medicine at Worthing and Southlands Hospitals Trust,
Worthing, West Sussex, UK. Competing interests: none declared.
Serene Ho MBBS BSc MRCP is a Senior House Officer in Renal and General
Medicine at Worthing and Southlands Hospitals Trust, Worthing, West
Sussex, UK. Competing interests: none declared.
Lui G Forni MBBS BSc PhD MRCPI is Consultant Physician and Intensivist
at Worthing and Southlands Hospitals Trust, Worthing, West Sussex,
UK, and Honorary Senior Lecturer at the Brighton and Sussex Medical
School, UK. Competing interests: none declared.

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Acute renal failure

and volume derangements. This should be allied to optimal

nutritional support ensuring adequate calorific intake whilst
limiting nitrogenous waste production and potassium intake.
Sepsis should be treated aggressively and ulcer prophylaxis with
proton pump inhibitors should be initiated.

and fluid-input charts need to include all fluid losses, including

estimated insensible losses as well as drain/stoma output and
nasogastric losses where appropriate. If possible, daily weight
measurement should be undertaken. Ideally, a central venous
catheter and an arterial cannula are required, particularly where
multiorgan failure (MOF) is precipitant. In established MOF, further invasive monitoring may be required as absolute measurement of central venous pressure may be misleading especially in
the ventilated patient where high intrathoracic pressures may be
present.
Where volume overload is encountered in the setting of ARF,
symptoms can be alleviated with high-flow oxygen or, where necessary, non-invasive ventilation by continuous positive airway
pressure ventilation (CPAP) where pulmonary oedema is refractory to pharmacological management whilst preparing the patient
for urgent RRT. The use of diuretics, such as frusemide and mannitol, as well as low-dose dopamine in ARF have yielded inconsistent results when subject to rigorous scrutiny.10,11 Although
loop diuretics may promote diuresis in oliguric renal failure there
is little evidence that they influence outcome.12 Furthermore,
the large doses of frusemide often required for diuresis in ARF
can result in ototoxicity. Similarly, the use of dopamine does not
reduce mortality or accelerate the recovery of renal function and,
in the critically ill, dopamine use is not without risk.

Addressing the cause

Classically the major causes of ARF are grouped into three
general categories: pre-renal causes, intrinsic renal causes and
obstruction. Pre-renal failure is responsible for up to 6070% of
ARF and is due in most cases to hypovolaemia, relative hypotension or renal hypoperfusion.7 In keeping with prevention of ARF,
potential nephrotoxins should be avoided and restoration of the
circulation should be attempted through careful volume resuscitation and/or through vasopressors. Intrinsic renal disease and
its management is beyond the scope of this review.
Histologically, acute tubular necrosis remains the most common cause.1,7 Although post-renal causes account for only 515%
of cases of ARF, it is important to recognize as prompt intervention may result in complete recovery of renal function. Clinical
assessment should include assessment for an enlarged bladder,
and prostate examination where applicable, and in the catheterized patient the urinary catheter should be changed if obstruction
is suspected. The investigation of choice is an abdominal ultrasound. Relief of obstruction may lead to a significant diuresis,
which may lead to volume depletion and consequent worsening
of renal function. Therefore careful monitoring of fluid balance is
mandatory (see also pages 42022).

Hyperkalaemia
This life-threatening complication requires immediate treatment
and arises through cellular shifts of potassium or release from
lysed cells together with decreased renal excretion of potassium.
Acidosis, hyponatraemia and hypocalcaemia all potentiate the
deleterious effects of hyperkalaemia on cardiac function and
hence must also be corrected. Presentation is non-specific, muscle weakness may be present, which if severe can lead to flaccid
paralysis, although symptoms rarely manifest until the plasma
potassium concentration exceeds 7.0 mmol/l. The most serious
concern is the effect on cardiac conduction, which classically
presents as a shortened QT interval with a tall peaked T wave
on the electrocardiograph (ECG). Progressive lengthening of the
QRS duration and the PR interval without treatment ultimately
progresses to a sine wave followed by ventricular standstill
or fibrillation. A variety of other conduction disturbances may
occur including bundle-branch block (left or right), bifascicular block and advanced atrioventricular block. All patients with
ARF should have continuous cardiac monitoring and immediate
therapy is warranted if ECG changes or neuromuscular abnormalities occur. Asymptomatic patients with a plasma potassium
concentration of less than 6.5 mmol/l or whose ECG does not
manifest signs of hyperkalemia can be treated with a cation
exchange resin, such as calcium resonium, and a low potassium
diet. Additional sources of potassium intake should be stopped
and any potentiating drugs discontinued.
Specific treatment of hyperkalaemia is directed at removing
excess potassium, shifting extracellular potassium into the cells
or antagonizing its membrane effects. Calcium directly antagonizes the actions of hyperkalaemia and, although short-lived, the
effect begins within minutes. Hyperinsulinaemia can be achieved
through giving insulin and glucose intravenously which stimulates Na/K-ATPase activity, causing a shift of potassium into
cells. Effective therapy usually leads to a 0.51.5 mmol/l fall in

Specific problems
Volume resuscitation
In hypovolaemia, volume expansion is recommended. However,
uncontrolled volume substitution may result in clinical deterioration and should be avoided. Isotonic crystalloids remain the
mainstay of volume replacement therapy correcting sodium
depletion as well as restoring solute and water diuresis. Crystalloids expand plasma volume by about 25% of the infused volume however, large-volume saline infusion can be associated
with a hyperchloraemic acidosis which may be associated with
renal vasoconstriction and gut hypoperfusion.8 Colloids, which
include albumin, gelatins and hydroxyethyl starch, result in volume expansion approximate to the infused volume. These should
be used with caution in ARF due to the associated risk of osmotic
nephrosis (osmotic tubular damage) if administered in isolation,
although a recent study comparing the use of 4% albumin compared to saline failed to demonstrate any significant differences
in outcome.9 The hydroxyethyl starches are highly polymerized
sugars characterized by their molecular weight, grade of substitu
tion and concentration. They are degraded through hydrolytic
cleavage, the remnants of which are excreted by the kidney, and
should be avoided in ARF particularly when due to sepsis.
Volume overload
The volume status of a patient with ARF needs to be assessed
carefully. Although somewhat unfashionable, careful bedside
examination including assessment of the venous pressure, capillary refill time, pulse and postural blood pressure changes are
elementary tool for assessing volume status. Hourly urine-output

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Acute renal failure

the plasma potassium concentration within 15 minutes, and the

maximal effect is observed after approximately 60 minutes. Similar
effects can be achieved with sodium bicarbonate solutions and
although this can correct acidosis its use may be limited in ARF
given the potential problems with volume balance. 2-adrenergic
agonists may also act directly on Na/K-ATPase activity and may
also be used effectively to treat hyperkalaemia but should be
avoided in patients with known active coronary disease. If these
conservative measures are ineffective and/or the hyperkalaemia is
severe then RRT should be employed.

resolve with treatment, although mental state may not improve

for up to 48 hours. If the signs do not resolve then other
pathologies need to be excluded.
Renal replacement therapy
Renal replacement therapy (RRT) does not cure acute renal failure
but it is a safe and efficient way of replacing renal function while
the kidneys recover from disease or injury. Historically, singleorgan ARF has been treated with either peritoneal or haemodialysis which are the mainstay of chronic renal replacement therapy.
Hospitals with acute nephrology services will perform haemodialysis in haemodynamically stable patients although acutely, RRT
is most commonly performed in a level 2 or 3 facility employing
either haemodialysis or more commonly haemofiltration. Although
superficially similar the mechanisms by which the composition of
the blood is altered, differ markedly.1517 In haemodialysis, blood
flows along one side of a semipermeable membrane as a solution
of crystalloids, the dialysis fluid, is pumped against the direction
of the blood flow along the other side of the membrane (see pages
46165). Molecules diffuse across the membrane from higher
to lower concentrations driven by the law of mass action. The
composition of the dialysis fluid allows as near normalization of
the plasma as possible. The dialysis-fluid compartment is under
lower pressure and this generates a transmembrane pressure gradient enabling the removal of salt and water. Haemofiltration in
its simplest form involves the passage of blood under pressure
passing down one side of a highly permeable membrane allowing
water and other molecules up to a size of c. 20 kD to pass through
the membrane through convection. Thus filtrate is discarded and
replaced by an idealized buffered replacement fluid the crystalloid components of which are at physiological levels. Although the
technique of haemofiltration has been refined and is also being
used in the treatment of sepsis using so-called high-flux systems,
the basic principles remain the same.18
Indications for renal replacement depend on the clinical and
biochemical derangements outlined above and, although these
are general indications, use will be guided by the clinical situa
tion. In the intensive care unit, for example, treatment may begin
before the absolute indications are reached with uncertainty surrounding the optimal timing of the initiation of renal support.
There is some evidence that in the critically ill intensive,
early treatment may result in improved outcomes but to date
no randomized clinical trials have specifically addressed this
question (Table 1).

Acidosis
Metabolic acidosis in ARF results from increased acid production, increased acid retention and decreased renal reabsorption
of bicarbonate. Acidosis is exacerbated by sepsis, malnutrition and some drugs. Mild acidosis (pH > 7.2) can usually be
reversed with adequate volume resuscitation. Sodium bicarbonate either intravenously or orally may be used if the acidosis is
severe (pH <7.2 or HCO3 1015mmol/l). Although some authors
express caution with regard to the generation of a paradoxical
acidosis on bicarbonate administration, in clinical practice this
is not a problem. The argument stems from the observation that
on addition of sodium bicarbonate to a weakly acidified solution
CO2 is generated. Since there is no significant gradient between
intracellular and extracellular CO2 it is argued that this results in
an increase in intracellular CO2, thus worsening the acidosis. The
evidence for this comes from in vitro work far removed from the
physiological, as well as animal work where predetermined ventilatory restraints were imposed. In effect these studies have used
a closed system whereas in spontaneously breathing patients,
or indeed one being adequately mechanically ventilated, the system is open allowing for CO2 removal.13,14 However, if large
volumes of isotonic sodium bicarbonate in ARF are employed,
they should be used with caution due to observed volume expansion and development of hypernatraemia.
Uraemic pericarditis
Uraemic pericarditis is observed in 610% of patients with
advanced renal failure resulting from inflammation of both the
visceral and parietal membranes of the pericardial sac. Pericarditis in ARF presents with fever and pleuritic chest pain characteristically worse in the recumbent position and a pericardial rub
may be heard on auscultation, although the ECG does not show
the typical diffuse ST and T wave elevations observed with other
causes of acute pericarditis. The development of pericarditis in a
patient with ARF is an indication to institute RRT unless there are
signs of cardiac tamponade due to a pericardial effusion. Under
such conditions, heparin-free hemodialysis or haemofiltration
should be used due to the risk of increased bleeding into the
pericardial sac with anticoagulation.

Practical aspects of renal replacement therapy

In both haemodialysis and haemofiltration access to the circula
tion is required and a variety of double-lumen vascular catheters are commercially available allowing blood flow rates up
to 200 ml/min. Adequate venous access is critical in preventing
technical difficulties with blood flow from the patient and potential problems with clotting leading to a loss of the extracorporeal
circuit. In most cases anticoagulation is required, with unfractionated heparin being commonly used to prime the circuits, and a
continuous infusion is maintained through the inflow side of the
circuit. If the patient is thrombocytopenic then alternative anticoagulants can be used, including saline, citrate or prostacyclin,
but care must be taken with the latter given its vasodilatatory
effects.

Uraemic encephalopathy
Uraemic encephalopathy together with uraemic pericarditis tends
to be related to the degree of uraemia. Early clinical features
include rambling speech, disorientation, lethargy, irritability and
hallucinations and, more rarely, coma. Commonly encountered
signs include tremor, myoclonus, and asterixis which tend to
occur with deterioration in mental status. Rarely, transient focal
signs may occur such as hemiparesis or reflex asymmetry but

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Acute renal failure

6 Goldenberg I, Matetzky S. Nephropathy induced by contrast media:

pathogenesis, risk factors and preventive strategies. CMAJ 2005;
172: 146171.
7 Rahman TM, Treacher DF. Management of acute renal failure on the
intensive care unit. Clin Med JRCPL 2002; 2: 10813.
8 Wilkes NJ, Woolf R, Mutch M, et al. The effects of balanced versus
saline-based hetastarch and crystalloid solutions on acid-base and
electrolyte status and gastric mucosal perfusion in elderly surgical
patients. Anesth Analg 2001; 93: 81116.
9 Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and
saline for fluid resuscitation in the intensive care unit. N Engl J Med
2004; 350: 224756.
10 Uchino S, Doig GS, Bellomo R, et al. Diuretics and mortality in acute
renal failure. Crit Care Med 2004; 32: 166977.
11 Kellum JA, Decker M. Use of dopamine in acute renal failure:
a meta-analysis. Crit Care Med 2001; 29: 152631.
12 Mehta RL, Chertow GM. Diuretics in critically ill patients with acute
renal failure. JAMA 2003; 289: 137981.
13 Goldsmith DJ, Forni LG, Hilton PJ. Bicarbonate therapy and
intracellular acidosis. Clin Sci 1997; 93: 59398.
14 Hilton PJ, Taylor J, Forni LG, Treacher DF. Bicarbonate-based
haemofiltration in the management of acute renal failure with lactic
acidosis. QJM 1998; 91: 27983.
15 Forni LG, Hilton PJ. Continuous hemofiltration in the treatment of
acute renal failure. N Engl J Med 1997; 336: 130309.
16 DIntini V, Ronco C, Bonello M, Bellomo R. Renal replacement
therapy in acute renal failure. Best Pract Res Clin Anaesthesiol
2004; 18: 14557.
17 Palevsky PM. Dialysis modality and dosing strategy in acute renal
failure. Semin Dial 2006; 19: 16570.
18 Mehta RL, McDonald B, Gabbai FB, et al. A randomized clinical trial
of continuous versus intermittent dialysis for acute renal failure.
Kidney Int 2001; 60: 115463.
19 Vinsonneau C, Camus C, Combes A, et al. Continuous venovenous
haemofiltration versus intermittent haemodialysis for acute renal
failure in patients with multiple-organ dysfunction syndrome:
a multicentre randomized trial. Lancet 2006; 368: 37985.
20 Honor PM, Joannes-Boyau O. High volume hemofiltration (HVHF)
in sepsis: a comprehensive review of rationale, clinical applicability,
potential indications and recommendations for future research.
Int J Artif Organs 2004; 27: 107782.

Indications for commencing renal replacement therapy

Clinical

Biochemical

Fluid overload with

increasing O2 requirement
Uraemic encephalopathy

Hyperkalaemia resistant to
medical therapy
Acidosis resistant to medical
therapy
Drug overdosage, e.g. lithium

Uraemic pericarditis
Table 1

Continuous haemofiltration is a highly effective system for the

replacement of renal function in patients with ARF. Although
only a few trials have compared continuous versus intermittent
techniques as yet no evidence exists to favour one technique
over the other. Where studies have been performed these unfortunately have not supplied the answer due to problems in study
design.19,20 The relative ease of continuous veno-venous haemofiltration (CVVH) together with its minimal haemodynamic
effects make it the treatment of choice in acute renal failure
especially when complicated by other organ failure.

References
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2007 Elsevier Ltd. All rights reserved.