Acute kidney failure, or more accurately, acute kidney injury (AKI), is characterised by a rapid fall in glomerular filtration rate resulting in an abrupt rise in urea and creatinine, usually associated with oliguria or anuria. The RIFLE criteria for the classification of AKI have been shown to predict outcome (see box).
AKI is increasingly common, accounting for 1 per cent of admissions to hospital and complicating more than 7 per cent of inpatient episodes, mostly in patients with pre-existing chronic kidney disease (CKD) and in older people.2
Patients at risk include those with diabetes, cardiac or vascular disease. Additional risk factors include the presence of hypovolaemia, hypotension or sepsis, and the use of certain drugs, particularly diuretics, angiotensin II-receptor blockers (ARBs) and NSAIDs.
Aetiology and outcome
Pre-renal AKI is caused by reduced kidney blood flow, for example due to hypovolaemia, hypotension or renal artery disease. Post-renal AKI is caused by urinary tract obstruction.
Intra-renal AKI is caused by renal parenchymal injury, which may involve the glomeruli, the tubules, the interstitium or the intra-renal vasculature (see box).
AKI is usually secondary to volume depletion and/or relative hypotension. If uncorrected, acute tubular necrosis (ATN) ensues; this may last days or weeks and may be associated with irreversible nephron loss.
Around 70 per cent of patients with AKI will achieve full renal recovery,3 but recovery is less likely (only 35 per cent) in patients with pre-existing CKD.
Only 50 per cent of patients with AKI are still alive at six months3 and the majority of patients who die (33 per cent) do so during the initial hospital admission.
Mortality rates are even higher in patients with sepsis or in the critically ill.
Despite advances in supportive care, survival rates have not improved over the last few decades, which may reflect the fact that progressively older patients with more pre-existing health problems are being referred for treatment. Contributed by Dr Stephan Brincat, specialist registrar, and Dr Rachel Hilton, consultant nephrologist at Guy's and St Thomas' NHS Foundation Trust.
|AKI classified by RIFLE criteria1|
|Serum||Glomerular filtration rate||Urine output||Duration|
|Risk of kidney dysfunction||>50% increase ||>25% decrease ||<0.5ml/kg/hour||>6 hours|
|Injury to the kidney||>two-fold increase|| >50% decrease||<0.5ml/kg/hour||>12 hours|
|Failure of kidney function||>three-fold increase OR >350μmol/l|| >75% decrease|
|Loss of kidney function||Loss of kidney function ||>4 weeks but <3 months|
|End stage kidney disease||Loss of kidney function|| >3 months|
|Principal causes of AKI|
|Reduced renal blood flow||Glomeruli||Renal tubules||Renal interstitium||Intra-renal vasculature||Urinary tract obstruction|
|Hypotension, Inflammatory e.g. cardiogenic or anaphylactic shock||Inflammatory e.g. glomerulonephritis||Ischaemic, e.g.prolonged renal hypoperfusion||Drug induced e.g.NSAIDs antibiotics||Vasculitis often ANCA-associated)||Intrinsic e.g. stones, bladder tumours|
|Hypovolaemia, e.g bleeding, vomiting, diarrhoea||Thrombotic, e.g accelerated hypertension, HUS/TTP||Toxic, e.g NSAIDs, radiocontrast, myoglobin, urate crystals||Granulomatous e.g. sarcoidosis||Cholesterol emboli||Extrinsic, e.g prostatic hypertrophy, pelvic malignancy|
|Renal artery disease e.g. severe stenosis or occlusion||Metabolic, e.g. hypercalcaemia, immunoglobulin light chains||Infiltrative, e.g. lymphoma|
| ANCA - anti-neutrophilic cytoplasmic antibodies; HUS - haemolytic|
uraemic syndrome; TTP - thrombotic thrombocytopaenic purpura
Section 2: Clinical features
The clinical history and examination findings are often more revealing than laboratory investigations in establishing the diagnosis.
The following questions should be considered: is this acute or chronic kidney disease? Has obstruction been excluded? Is the patient euvolaemic? Is there any evidence of renal parenchymal disease (other than ATN)?
Clinical history includes
- Presence of any pre-existing conditions such as diabetes, hypertension, cardiac or vascular disease, CKD or urinary tract problems such as prostatic hypertrophy or previous stones.
- Presence of any recent acute illness associated with reduced fluid intake or excessive fluid loss such as diarrhoea or vomiting.
- Introduction of any new medication, particularly antibiotics, NSAIDs, ACE inhibitors or ARBs, but also OTC medications and herbal remedies.
- Presence of any symptoms suggestive of systemic illness such as joint pains, myalgia, skin rashes, new-onset deafness, recurrent sinusitis or haemoptysis.
- Presence of any symptoms suggestive of advanced CKD such as fatigue, anorexia, nausea, vomiting, weight loss, itching, nocturia or hiccups.
- Presence of any family history of kidney disease.
- Assessment of volume status including observation of pulse rate, BP and jugular venous pressure, inspection for dry mouth and reduced skin turgor, auscultation for pulmonary crepitations and inspection for peripheral oedema.
- Identification of any features of systemic disease such as fever, splinter haemorrhages, skin rashes, joint swelling or tenderness, iritis or scleritis and presence of new heart murmurs.
- Identification of any evidence of vascular disease such as cool peripheries, absent peripheral pulses or palpable abdominal aortic aneurysm.
- Identification of any evidence of advanced CKD such as pallor, uraemic pigmentation, excoriations, foetor or pericardial rub.
- Identification of features of long-standing or severe hypertension, in particular evidence of hypertensive retinopathy, including arterio-venous nipping, haemorrhages, exudates or papilloedema.
- Identification of any evidence of bladder outflow obstruction principally assessment for a palpable bladder.
Section 3: Investigation and diagnosis
When a patient is found to have a raised serum creatinine it is important to distinguish between AKI and CKD, as the approach to these patients differs greatly.
The most useful clue comes from previous creatinine measurements if these are available. If the baseline creatinine is not known it is safest to assume that this was normal and that the patient has AKI.
If the patient is well and there are no life-threatening complications such as volume overload, hyperkalaemia or acidosis, it may be worth repeating the blood test to exclude a spurious result. This should be arranged promptly, within a maximum of five days.
Urine dipstick and microscopy are mandatory to avoid missing a renal inflammatory process (see box).
Dipstick blood or protein, or dysmorphic red cells, red cell casts (suggestive of glomerulonephritis) or eosinophils (suggestive of acute interstitial nephritis) on microscopy warrants prompt referral to a nephrologist.
The following tests may be performed in hospital, often tailored according to the individual circumstances.
- Kidney ultrasound: to assess size and exclude obstruction.
- Immunological tests such as antinuclear antibody, anti-double-stranded DNA antibodies, ANCA and anti-glomerular basement membrane antibodies are performed to exclude a renal inflammatory process.
- Serum protein electrophoresis and urinary Bence Jones protein, to exclude multiple myeloma.
A kidney biopsy may assist in establishing the diagnosis, planning treatment and assessing prognosis. Common indications include AKI with haematuria and/or proteinuria, persistent AKI of unknown cause, and AKI with clinical or serological evidence of a renal inflammatory process as discussed above.
Kidney biopsy carries a risk of bleeding and other complications so the risks and benefits for each patient are decided on an individual basis.
|Urinalysis in AKI|
|Urine dipstick||Reduced renal blood flow||Glomerular disease||Tubular damage||Interstitial disease||Urinary tract obstruction|
|Blood||Negative||Strongly positive (2+ to 4+)||Negative||May be positive (Trace to 1+)||Usually negative*|
|Protein||Negative||Strongly positive (2+ to 4+)||May be positive (Trace to 2+)||May be positive (Trace to 2+)||Usually negative*|
|* unless co-existent infection|
Section 4: Management and prevention
AKI is a medical emergency with high morbidity and mortality. As it is often preventable, it is crucial to identify at-risk patients. In incipient or established AKI, rapid recognition and treatment may prevent irreversible nephron loss. Specialist advice should always be sought as early consultation can improve outcomes.
Increasingly, the immediate care of patients with AKI and the provision of emergency renal replacement therapy fall within the remit of critical care specialists in intensive care units. However, when the cause is not apparent or there is suspicion of renal parenchymal disease (other than ATN), urgent consultation with a nephrologist is essential.
Management of established AKI encompasses general measures irrespective of cause and specific therapies targeted to the particular aetiology (beyond the scope of this review).
Acute tubular necrosis
The most common cause of AKI is ATN, for which the treatment is supportive, the key principles being:
- Identification and treatment of acute complications, such as hyperkalaemia, acidosis and pulmonary oedema.
- Identification and correction of pre-renal and post-renal factors: restoration of adequate circulating volume with appropriate fluids; relief of obstruction if present.
- Review of medication: cessation of nephrotoxic drugs; dosage adjustment of other drugs where appropriate.
- Accurate monitoring of fluid balance and daily weight.
- Optimisation of nutrition to ensure adequate calories, minimal nitrogenous waste and restriction of dietary potassium.
- Identification and treatment of infection: removal of indwelling lines and catheters wherever possible.
- Identification and treatment of any bleeding tendency: administration of an H2 antagonist or proton pump inhibitor to prevent GI bleeding; avoidance of aspirin.
- Referral for dialysis before uraemic complications develop. Absolute indications for dialysis include resistant hyperkalaemia, resistant pulmonary oedema, resistant acidosis, uraemic encephalopathy or pericarditis.
Despite much research, to date no pharmacological therapy has been shown to limit the progression of, or speed up the recovery from, AKI and some drugs such as loop diuretics, dopamine or mannitol may be harmful.4
The mainstay of prevention of AKI is to identify at-risk patients, including elderly people and those patients with diabetes, hypertension or vascular disease. As well as identifying patients with a pre-existing renal impairment.
In at-risk patients preventative measures include maintenance of adequate intravascular volume and BP to avoid pre-renal AKI secondary to hypovolaemia and hypotension, and avoidance of potentially nephrotoxic agents, particularly NSAIDs, ACE inhibitors or ARBs.
AKI remains a devastating illness with high mortality despite advances in supportive care. The pathophysiology is poorly understood and therapeutic options are limited.
In most episodes of AKI initial management is by non specialists, and community-acquired AKI accounts for a significant proportion of hospital admissions.
All clinicians should therefore be able to recognise the symptoms and signs of AKI, request and interpret initial investigations, start appropriate treatment, and know when, and how urgently, to seek specialist advice.
1. Venkataraman R, Kellum J. Defining acute renal failure: the RIFLE criteria. J Intensive Care Med 2007; 22: 187-93.
2. Hilton R. Acute renal failure. BMJ 2006; 333: 786-90.
3. Ali T, Khan I, Simpson W et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol 2007; 18: 1,292-8.
4. Kellum J, Leblanc M, Venkataraman R. Renal failure (acute) Clin Evid 2006; 15: 1,191-212
- Glynne P, Allen A, Pusey C. Acute renal failure in practice. London: Imperial College Press, 2002.
- Firth J. The clinical approach to the patient with acute renal failure. Oxford Textbook of Clinical nephrology, 3rd ed. Oxford: Oxford University Press, 2005: 1,465-93.