Acute Renal Failure (ARF)

Acute renal failure (ARF) is characterised by a rapid fall in glomerular filtration rate,
clinically manifest as an abrupt and sustained rise in urea and creatinine.1 Definitions of
acute renal failure range from severe (i.e. requiring dialysis) to slight increases in serum
creatinine concentration. In the absence of a universal definition, acute renal failure is
often defined as a significant deterioration in renal function occurring over hours or
days.2 There may be no symptoms or signs, but oliguria (urine volume less than 400
mL/24 hours) is common. There is an accumulation of fluid and nitrogenous waste
products demonstrated by a rise in blood urea and creatinine.
Causes of acute renal failure1

• Prerenal:

• Volume depletion (e.g. haemorrhage, severe vomiting or diarrhoea, burns,

inappropriate diuresis)

• Oedematous states: cardiac failure, cirrhosis, nephrotic syndrome

• Ηψ π ο τ ε ν σ ι ο ν (e.g. cardiogenic shock, sepsis, anaphylaxis)

• Cardiovascular (e.g. severe cardiac failure, arrhythmias)

• Renal hypoperfusion: non-steroidal anti-inflammatory drugs or selective

cyclo-oxygenase 2 inhibitors, ACE inhibitors or angiotensin II receptor
antagonists, abdominal aortic aneurysm, renal artery stenosis or occlusion,
hepatorenal syndrome

• Intrinsic ARF:

• Glomerular disease: glomerulonephritis, thrombosis, haemolytic uraemic

syndrome

• Tubular injury: acute tubular necrosis following prolonged ischaemia;

nephrotoxins (e.g. aminoglycosides, radiocontrast media, myoglobin,
cisplatin, heavy metals, light chains in myeloma kidney)

• Αχ υ τ ε ιντ ε ρ σ τ ι τ ι α λ νεπη ρ ι τ ι σ due to

drugs (e.g. NSAIDs), infection or autoimmune diseases

• Vascular disease: vasculitis (usually associated with antineutrophil

cytoplasmic antibody), cryoglobulinaemia, polyarteritis nodosa,
thrombotic microangiopathy, cholesterol emboli, renal artery stenosis,
renal vein thrombosis, malignant hypertension

• Eclampsia

• Post-renal:
 • Calculus

• Blood clot

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• Πρ ο σ τ α τ ι χ ηψ π ε ρ τ ρ ο π η ψ or malignancy

• Βλα δ δ ε ρ τυµ ο υ ρ

• Radiation fibrosis

• Pelvic malignancy

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Epidemiology

• Recent studies have found an overall incidence of acute renal failure of almost
500 per million per year and the incidence of acute renal failure needing dialysis
being more than 200 per million per year.1

• Prerenal ARF and ischaemic acute tubular necrosis together account for 75% of
the cases of acute renal failure.3
Risk factors1
People with the following comorbid conditions are at a higher risk for developing ARF:

• Elderly

• Hypertension

• Vascular disease

• Pre-existing renal impairment

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• Myeloma

• Chronic infection

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Presentation
The presentation will depend on the underlying cause and severity of acute renal failure.
The first indication may be a raised urea and creatinine on a blood test in a patient with
non-specific symptoms and signs.
Symptoms

• Urine output:

• Acute renal failure is usually accompanied by oliguria or anuria, but

polyuria may occur.

• Abrupt anuria suggests an acute obstruction, acute and severe

glomerulonephritis, or acute renal artery occlusion.

• Gradual diminution of urine output may indicate a urethral stricture or

bladder outlet obstruction, e.g. benign prostatic hyperplasia.

• Nausea, vomiting

• Dehydration

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Signs

• Hypertension

• Abdomen: may reveal a large, painless bladder typical of chronic urinary

retention

• Dehydration with postural hypotension and no oedema

• Fluid overload with raised JVP, pulmonary oedema and peripheral oedema

• Pallor, rash, bruising: petechiae, purpura, and nose bleeds may suggest
inflammatory or vascular disease, emboli or disseminated intravascular
coagulation

• Pericardial rub
Assessment1

• Distinguish acute and chronic renal failure (CRF):

• Factors that suggest CRF include long duration of symptoms, nocturia,

absence of acute illness, anaemia, hyperphosphataemia, hypocalcaemia.

• Previous creatinine measurements if available are very useful.

• Reduced renal size and cortical thickness on ultrasound is characteristic of

chronic renal failure (renal size is typically preserved in patients with
diabetes).
• Exclude urinary tract obstruction:

• History of previous stones or symptoms of bladder outflow obstruction

• Palpable bladder

• Complete anuria suggests renal tract obstruction

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dilatation of the renal pelvis and calyces (obstruction may be present
without dilatation, especially in patients with malignancy)

• Consider hypovolaemia:

• Low venous pressure and a postural fall in blood pressure

• Disproportionate rise in the plasma urea:creatinine ratio

• Low urinary sodium concentration (but use of diuretics makes urinary

indices unhelpful)

• Evidence of renal parenchymal disease:

• Features of underlying systemic disease, e.g. rashes, arthralgia, myalgia

• Use of antibiotics and non-steroidal anti-inflammatory drugs

• Urine dipstick and microscopy: dipstick blood or protein, or dysmorphic

red cells, red cell casts (suggestive of glomerulonephritis), or eosinophils
(suggestive of acute interstitial nephritis) on microscopy

• Consider major vascular occlusion:

• Occlusion of a normal renal artery results in loin pain and haematuria,

occlusion of a previously stenosed renal artery may be asymptomatic;
acute renal failure may be precipitated by occlusion (thrombotic or
embolic) of the artery supplying the remaining kidney.

• Renal asymmetry on imaging is suggestive, especially in a patient with

known vascular disease elsewhere.

• Risk factors include use of ACE inhibitors and diuretics in patient with
renal artery stenosis, hypotension or instrumentation of the renal artery or
aorta.

• Complete anuria occurs.

• Occlusion of a previously normal renal artery is uncommon, mostly

caused by embolisation from a central source.
Differential diagnosis

• Chronic renal failure: factors that suggest chronic renal failure include:

• Long duration of symptoms

• Nocturia

• Absence of acute illness

• Anaemia

• Hyperphosphataemia, hypocalcaemia (but similar laboratory findings may

complicate acute renal failure)

• Reduced renal size and cortical thickness on renal ultrasound (but renal
size is typically preserved in patients with diabetes

• Acute on chronic renal failure

Investigations

• Urinalysis:

• Urinalysis: blood and/or protein suggests a renal inflammatory process;

microscopy for cells, casts, crystals; red cell casts diagnostic in
glomerulonephritis; tubular cells or casts suggest acute tubular necrosis

• Urine osmolality: osmolality of urine is over 500 mOsm/kg if the cause is

pre-renal and 300 mOsm/kg or less if it is renal; patients with acute
tubular necrosis lose the ability to concentrate and dilute the urine and will
pass a constant volume with inappropriate osmolality

• Biochemistry:

• Serial urea, creatinine, electrolytes: important metabolic consequences of

ARF include hyperkalaemia, metabolic acidosis, hypocalcaemia,
hyperphosphataemia (serum urea is poor marker of renal function, because
it varies significantly with hydration diet, it is not produced constantly and
it is reabsorbed by the kidney).

• Serum creatinine has significant limitations. The level can remain within
the normal range despite the loss of over 50% of renal function.

• Creatine kinase, myoglobinuria: markedly elevated creatine kinase and

myoglobinuria suggest rhabdomyolysis.

• Haematology:

• Full blood count, blood film: eosinophilia may be present in acute

 interstitial nephritis, cholesterol embolisation, or vasculitis;
thrombocytopenia and red cell fragments suggest thrombotic
microangiopathy.

• Coagulation studies: disseminated intravascular coagulation associated

with sepsis.

• Immunology:

• C reactive protein: non-specific marker of infection or inflammation.

• Serum immunoglobulins, serum protein electrophoresis, Bence Jones

proteinuria: immune paresis, monoclonal band on serum protein
electrophoresis, and Bence Jones proteinuria suggest myeloma.

• Αν τ ι ν υ χ λ ε α ρ α ν τ ι β ο δ ψ (ANA): ANA positive in

SLE and other autoimmune disorders; anti-dsDNA antibodies more
specific for SLE; anti-double stranded (ds) DNA antibodies; antineutrophil
cytoplasmic antibody (ANCA) (associated with systemic vasculitis; c-
ANCA and anti-PR3 antibodies associated with Wegener's
granulomatosis; p-ANCA and anti-MPO antibodies present in microscopic
polyangiitis), antiproteinase 3 (PR3) antibodies, antimyeloperoxidase
(MPO) antibodies.

• Complement concentrations: low in SLE, acute postinfectious

glomerulonephritis, cryoglobulinaemia.

• Antiglomerular basement membrane antibodies: present in Goodpasture's

disease.

• Antistreptolysin O and anti-DNAse B titres: high after streptococcal

infection.

• Virology:

• Hepatitis B and C; HIV: important implications for infection control

within dialysis area

• Radiology:

• Renal ultrasonography: renal size, symmetry, evidence of obstruction

• Chest x-ray (pulmonary oedema); abdominal x-ray if renal calculi are

suspected

• Contrast studies such as IVU and renal angiography should be avoided

because of the risk of contrast nephropathy

• Doppler ultrasound of the renal artery and veins: assessment of possible

 occlusion of the renal artery and veins

• Magnetic resonance angiography: for more accurate assessment of renal

vascular occlusion

• ECG: recent myocardial infarction, tented T waves in hyperkalaemia

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Management
Principles of management of acute renal failure1

• Advice from a nephrologist should be sought for all cases of acute renal failure, as
early consultation can improve outcomes.

• No drug treatment has been shown to limit the progression of, or speed up
recovery from, acute renal failure.

• Identify and correct pre-renal and post-renal factors.

• Optimise cardiac output and renal blood flow.

• Review drugs: stop nephrotoxic agents; adjust doses and monitor concentrations
where appropriate.

• Accurately monitor fluid balance and daily body weight.

• Identify and treat acute complications (hyperkalaemia, acidosis, pulmonary

oedema).

• Optimise nutritional support: adequate calories, minimal nitrogenous waste

production, potassium restriction.

• Identify and aggressively treat infection; minimise indwelling lines; remove

bladder catheter if anuric.

• Identify and treat bleeding tendency: prophylaxis with proton pump inhibitor or
H2 antagonist, transfuse if required, avoid aspirin.

• Initiate dialysis before uraemic complications emerge.

• Renal specialists are not necessary for provision of renal replacement therapy, as
this can be initiated promptly in most intensive care units by continuous
venovenous haemofiltration.
Accurate control of fluid balance (avoid volume overload or depletion)

• Accurate measurement of urine output is essential to prevent volume overload or

depletion.
 • Most patients are oliguric and should be provided with a volume of fluid equal to
the output on the previous day, plus an extra 500 mL for insensible losses (more if
pyrexia is present). Twice daily clinical fluid balance assessment is required.
Fluid-balance charts are frequently inaccurate and unthinking adherence to the
output plus 500 mL rule may be inappropriate.4

• The situation may change rapidly and so daily clinical assessment, measurement
of body weight and CVP monitoring are required.

• Doses of frusemide may have to be in hundreds of milligrams per day. There is no

evidence to suggest that the use of loop diuretics reduces mortality, reduces length
of ITU/hospital stay, or increases the recovery of renal function.5,6

• Pulmonary oedema: requires high concentration oxygen, IV morphine, IV high

doses (250 mg) frusemide given over 1 hour, and IV nitrates.4 May also require
haemodialysis or haemofiltration if not responding to these measures.
Venesection and continuous positive airways pressure may be useful if the patient
is in extremis.

• If there is hypotension both noradrenaline and vasopressin may be beneficial.7

• There is no evidence for the use of low-dose dopamine infusions.

Daily measurement of serum electrolytes, potassium and sodium restriction,
nutritional support

• Potassium restriction is nearly always necessary and is typically limited to less

than 50 mmol/day.

• Acute hyperkalaemia may be managed with IV calcium gluconate and

dextrose/insulin infusions.

• In the slightly longer term, potassium-binding resins can be used if dialysis is not
immediately available.

• Sodium intake should be restricted to about 80 mmol/day, depending on losses.

• Acidosis may be limited by protein restriction, though a daily intake of at least

approximately 1 g of high-quality protein per kilogram of body weight is
necessary to maintain adequate nutrition.

• It is important to maintain adequate nutrition, preferably via the enteral route, but
using parenteral nutrition if necessary.

• Excretion of phosphate is impaired in renal failure; hyperphosphataemia should

be treated with calcium carbonate or other phosphate binders.3

• Nitrogen balance can be complex, especially with a hyper catabolic state and
possible gastrointestinal bleeding, and diarrhoea.
 • Sodium bicarbonate may be used cautiously to treat acidosis, but may worsen
sodium overload.
Hyperglycaemia adversely affects the prognosis for patients with acute renal failure;
there has been shown to be a reduction in mortality and morbidity of critically ill
patients with strict control of blood glucose concentration.3
Prevention of infection

• Patients in renal failure are susceptible to infection.

• Infection is a significant cause of mortality. Therefore strict sepsis control is

essential; avoidance of intravenous lines, bladder catheters, and respirators is
recommended.
Impaired haemostasis
Active bleeding may require:

• Fresh frozen plasma and platelets

• Blood transfusion

• Intravenous desmopressin (increases factor VIII coagulant activity; shown in

acute renal failure to shorten prolonged bleeding time;8 repeated doses have a
lesser effect)
Prevention of gastrointestinal haemorrhage

• Gastrointestinal haemorrhage is a potential cause of morbidity in ARF, and so

prophylactic treatment to reduce gastric acid secretion is generally indicated.
Careful drug dosing and avoidance of nephrotoxic drugs

• Doses must be adjusted and drug levels monitored accordingly.

• Nephrotoxic drugs, such as NSAIDs and aminoglycosides, should be avoided.

Specific treatment of underlying intrinsic renal disease where appropriate

• Acute renal artery thrombosis (of a single functioning kidney) may be treated
surgically, or by angioplasty and stenting.

• In rhabdomyolysis with myoglobulinuria, alkaline diuresis may prevent the

development of severe renal failure, but must be undertaken with care in oliguric
patients.

• Acute tubulointerstitial nephritis may respond to a short course of high-dose

corticosteroids, though no controlled trials have been undertaken to support this
approach.
 • ARF due to crescentic glomerulonephritis may respond to treatment with
prednisolone and cyclophosphamide, together with the addition of plasma
exchange.

• Haemolytic uraemic syndrome may respond to plasma exchange with fresh frozen
plasma.
Dialysis or haemofiltration

• In oliguric or anuric patients, the fluid intake required for feeding generally means
that dialysis will be necessary.

• Peritoneal dialysis is usually only performed when haemodialysis is unavailable.

• In patients who are haemodynamically unstable, continuous dialysis techniques

(e.g. haemodiafiltration) are better tolerated than intermittent haemodialysis and
allow more effective control of fluid balance.

• Indications for dialysis in acute renal failure:4,3

• Urea >25-30 mmol/l and creatinine >500-700 micromol/l, unless clear

evidence that recovery is under way

• Refractory hyperkalaemia

• Intractable fluid overload

• Acidosis producing circulatory compromise

• Overt uraemia manifesting as encephalopathy, pericarditis, or uraemic

bleeding

• Oliguria with urine output less than 200 mL/12 hours

• Acidaemia (pH<7.0)

• Toxicity with drugs that can be dialysed

• Hyperthermia
Complications
Life threatening complications include:

• Volume overload (severe pulmonary oedema)

• Hyperkalaemia

• Metabolic acidosis

• Spontaneous haemorrhage, e.g. gastrointestinal

Prognosis

• When acute renal failure is severe enough to need dialysis, in-hospital mortality is
around 50%, and it may exceed 75% in the context of sepsis or in critically ill
patients.1

• The prognosis is closely related to the underlying cause. In prerenal failure,

correction of volume depletion, using central venous pressure monitoring when
necessary, should result in rapid recovery of renal function. However, once ATN
has developed, and in other causes of ARF, the patient will often be oliguric for
several days or weeks.

• If there is not a significant return of renal function within 6 to 8 weeks this usually
means that there is end stage renal failure but rarely late recovery can occur.

• Prognosis is improved by rapid and aggressive treatment. This includes correcting

pre-renal causes like hypovolaemia or inserting stents to bypass obstruction in
post-renal causes.

• Patients who need dialysis have a higher mortality but this is a reflection of the
condition rather than a result of the treatment.

• Within an intensive care setting, mortality varies from 7.5% to 40% and outside
of intensive care from zero to 17%.

• The Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring
system indicates prognosis. In those who have a score between 10 and 19 the
mortality rate is 60% but with a score above 40 it approaches 100%.9

• Another system to help indicate prognosis and to aid classification for research
purposes is called RIFLE and was developed by the Acute Dialysis Quality
Initiative Workgroup. The first 3 items are risk, injury and failure. The last two
are outcomes or loss and end-stage renal failure.10

• Indicators of poor prognosis include older age, multiple organ failure, oliguria,
hypotension, number of transfusions and acute on chronic renal failure.
Prevention

• Identification of patients at risk.

• Maintain adequate blood pressure and volume status.

• Avoid potentially nephrotoxic agents, especially NSAIDs, ACE inhibitors or

angiotensin II receptor blockers.

• Acetylcysteine plus volume expansion may be used for prevention of contrast

nephropathy