Clinical Review: Acute kidney injury

Contributed by Dr Hannah Kilbride, specialist registrar, and Dr Marlies Ostermann, consultant in nephrology and critical care, Guy's and St Thomas' NHS Foundation Trust, London.

Haemodialysis or haemofiltration should be started before the onset of potentially fatal complications (Photograph: SPL)
Haemodialysis or haemofiltration should be started before the onset of potentially fatal complications (Photograph: SPL)

Section 1: Epidemiology and aetiology
Acute kidney injury (AKI), previously termed acute renal failure, is a complex disorder with multiple aetiologies and risk factors.

It arises from a rapid fall in kidney function over hours to days and is often preventable and reversible.

The importance of AKI on patient outcomes was emphasised in 2009 by the National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) report on hospitalised patients, which identified failings in the recognition and management of AKI.

The prevalence of AKI depends on the population studied and the criteria used. Attempts to agree on a universal definition of AKI resulted in the RIFLE (risk, injury, failure, loss, end-stage disease) criteria followed by the AKI Network classification, both of which are based on changes in serum creatinine and/or urine output.1,2

Recently the international guideline group Kidney Disease: Improving Global Outcomes (KDIGO) produced a definition and staging system based on the RIFLE and AKI Network classification which is due to be published later in 2011 and is likely to be adopted globally.

The population incidence of AKI in the UK ranges from 172 per million population (pmp) per year from early data up to 486-630 pmp/year from more recent studies, depending on definition.3,4

The incidence is higher in hospitalised patients occurring in up to 18 per cent of all hospital admissions with reports of up to 65 per cent in critically ill patients in the ICU.

Acute Kidney Injury Network classification

AKI definition: An abrupt (within 48 hours) reduction in kidney function defined as an absolute increase in serum creatinine of either ≥0.3mg/dl (≥26.4micromol/L) or a percentage increase of ≥50 per cent (1.5 fold from baseline) or a reduction in urine output.

AKI staging:

AKI stage Serum creatinine criteria Urine output criteria
1  ↑ SCr ≥26.4micromol/L or
 ↑ SCr ≥150–200 per cent
(1.5–2 fold) from baseline.
<0.5ml/kg/h for >six hours.
2  ↑ SCr >200–300 per cent
(>2–3 fold) from baseline.
<0.5ml/kg/h for >12 hours.
3  ↑ SCr >300 per cent (>3fold) from baseline or SCr ≥354micromol/L with an acute rise of ≥44micromol/L or treatment with renal replacement therapy. SCr >300 per cent (>3fold) from baseline or SCr ≥354micromol/L with an acute rise of ≥44micromol/L or treatment with renal replacement therapy. <0.3ml/kg/h for
24 hours or anuria for 12 hours.
SCr: Serum creatinine. Only one criterion must be met of either the SCr criteria or the urine output criteria; if both are present, the criterion which places the patient in the higher stage of AKI is selected.

Risk factors
Several risk factors have been identified for the development of AKI (see box, above). Elderly patients and patients with pre-existing chronic kidney disease (CKD) are at particular risk.

The causes are grouped into pre-renal (for example, hypovolaemia and/or relative hypotension), intrinsic renal (for example, damage of glomeruli, renal vasculature, tubules and/or interstitium) and post-renal (for example, obstruction to urinary flow).

The most common cause of intrinsic AKI is acute tubular necrosis (ATN), which is usually multifactorial and often occurs in the context of an acute illness.

The exact aetiology of AKI is not always obvious and occasionally more than one factor contributes to its development.

Risk factors for development of AKI
Comorbidities Clinical conditions Drugs

Advanced age
Heart failure
Liver failure
Male gender
Genetic factors
Low albumin
Arterial disease

Volume depletion
Cardiac/vascular surgery
Non-renal solid organ transplant
Hepatic/biliary surgery
Contrast media
ACE inhibitor/ARB

Section 2: Making the diagnosis
AKI usually develops over hours to days and leads to an abrupt rise in serum urea and creatinine levels, electrolyte disturbances and metabolic acidosis. Urine output can be preserved but is often reduced.

Despite the fact that serum creatinine is affected by several non-renal factors, such as muscle bulk and gender, and takes 24 to 48 hours to rise after the initial renal insult, it remains the traditionally used parameter to diagnose AKI.

However, newer AKI biomarkers are being investigated and validated in clinical trials. The formula to estimate eGFR is based on observations in patients with stable CKD. eGFR has never been validated in patients with acute and rapid changes in renal function, and should only be used in situations where renal function is stable.

At present, the AKI Network classification is commonly used to diagnose AKI. It relies on knowing baseline renal function, which means it is important to look at previous results in order to differentiate AKI from pre-existing CKD.

Patients may be asymptomatic during the early stages of AKI, which may delay the diagnosis. If patients develop symptoms, they usually have non-specific complaints, such as nausea, tiredness, lack of appetite and possibly breathlessness.

These symptoms often mimic other less serious conditions, which again may delay the diagnosis, especially in the community.

In some cases, patients may develop symptoms and signs which point towards a potential aetiology, for instance flank pain in the case of underlying ureteric obstruction, or a rash with myalgia and eye changes as a result of an underlying connective tissue disease or systemic vasculitis.

Once AKI is diagnosed, investigations should focus on identifying the aetiology and ruling out complications of AKI (see box, below). As recommended by the NCEPOD report, all hospitalised patients with AKI should have a renal ultrasound within 24 hours to exclude underlying obstruction.

Diagnostic work-up of patients with AKI
Investigations Comments
To be performed during initial
assessment in
primary care
Urinalysis Presence of blood, protein and red cell casts suggest a glomerular cause; eosinophils suggest an interstitial nephritis.
Serum creatinine and UAEs To diagnose degree of AKI and electrolyte disturbances.
FBC and blood film Red cell fragments and thrombocytopaenia support the diagnosis of thrombotic microangiopathy; eosinophilia may be present with interstitial nephritis.
CRP May be elevated in inflammatory diseases and/or infections.

Section 3: Managing the condition
Studies have shown that up to 30 per cent of AKI episodes are iatrogenic and potentially preventable. According to the NCEPOD report, only 50 per cent of patients who died with AKI received good care and there was often an inadequate assessment and an unacceptable delay in recognising AKI.

Prevention of AKI is important, especially in high-risk and elderly patients. Preventive strategies include avoidance of nephrotoxic drugs, including contrast media, and timely resuscitation of patients suffering from sepsis and/or hypovolaemia. Diuretics have no role in preventing AKI.

Clinical examination
Once AKI has developed, a detailed medical history and thorough clinical examination are essential. Independent of the cause of AKI, patients should undergo correction of volume depletion, optimisation of haemodynamics, timely treatment of sepsis, discontinuation of any nephrotoxic drugs where possible and exclusion of underlying obstruction.

There is no specific pharmacological therapy proven to effectively treat AKI. However, certain types of AKI may respond to treatment of the underlying disease, for example, decompressive procedures for acute obstruction, immunosuppression for systemic vasculitis or crescentic glomerulonephritis, and plasma exchange for pulmonary renal syndrome.

Attention to detail and regular re-assessment of the patient are essential to detect signs of progressive AKI and development of life-threatening complications, including hyperkalaemia, severe acidosis, fluid overload and uraemic pericarditis.

Ideally, renal replacement therapy with haemodialysis or haemofiltration should be started before the onset of potentially fatal complications.

Effects on other organs
It is important to keep in mind that AKI affects the function of other organs. Patients have an increased risk of gastritis and increased bleeding tendency as a result of platelet dysfunction. The pharmacokinetics of several drugs may be altered, and the risk of acquiring new infections is increased.

Management in the community
Most patients with AKI are managed in hospital, often in the renal or critical care unit. Patients in the community may develop AKI that is not severe enough to require them to be hospitalised.

In this case, patients need to be followed up closely and have a repeat check of their renal function within two to three days of a newly raised creatinine.

If AKI worsens, discussion with the local renal unit is strongly advised.

Section 4: Prognosis
In patients with AKI, the chances of renal recovery and survival depend on the underlying aetiology, the duration of AKI and associated comorbidities. There is increasing recognition that AKI is associated with an increased risk of dying even after discharge 0from hospital.

A landmark study in almost 10,000 hospitalised patients showed that even minor rises in serum creatinine by 26micromol/L or more were independently associated with a four times higher risk of dying in hospital.5

AKI due to ATN is usually reversible. However, several reports have highlighted an association between AKI and subsequent risk of developing CKD, even if the episode of AKI resolves and serum creatinine returns to baseline.6,7

The burden of CKD in survivors of AKI and the numbers progressing to end-stage renal disease is still under-appreciated. There is a need for AKI survivors to have a clear post-discharge plan for follow up and management of residual renal dysfunction and cardiovascular risk factors. Close liaison between primary and secondary care after discharge from hospital is crucial.

Section 5: Case study
A 28-year-old woman presented with bilateral aching pain in her flanks, vomiting and general malaise. One month prior she had been diagnosed with a UTI and had a course of oral antibiotics. She had never completely recovered suffering with nausea, reduced appetite, fever and myalgia.

Urgent renal biopsy showed interstitial nephritis

Six months before, she had been prescribed oxytetracycline for acne, which she had stopped taking due to side-effects. She had not had a blood test and had no medical history. Her serum creatinine was 536micromol/L, CRP 46mg/L, white cell count 14x109/L and eosinophil count 1x109/L. Urinalysis showed 1+ protein and 1+ blood. She was volume depleted and had no heart murmurs.

Renal biopsy
An urgent ultrasound scan showed two unobstructed 10cm kidneys. She was transferred to the renal unit where she was volume repleted with IV fluids. An echocardiogram was performed to rule out valvular vegetation.

The differential diagnoses included acute glomerulonephritis, acute vasculitis or interstitial nephritis. The following day an urgent renal biopsy was performed which showed interstitial nephritis with eosinophilic infiltration, likely secondary to antibiotic reaction and acute tubular necrosis.

She had already discontinued her antibiotics and her renal function began to improve with IV fluids. Treatment with steroids was not indicated.

Her renal function returned to a baseline creatinine of 73micromol/L after two weeks and she was discharged to her GP for follow up.

Section 6: Evidence Base
Clinical trials

This study looked at the epidemiology of AKI in the US and found it was associated with a prolonged hospital stay of two days and an adjusted odds ratio of 4.1 for hospital mortality. It illustrated the cost effects of AKI on the health service.

This meta-analysis of nine RCTs found that furosemide is not associated with any clinical benefits in the prevention and treatment of AKI, but increases the risk of ototoxicity.   


  • DoH. National service framework for renal services – part two: Chronic kidney disease acute renal failure and end of life care. DoH, London, 2010.
  • NICE. Acutely ill patients in hospital. CG50, NICE, London, 2007.
  • The Renal Association. Acute kidney injury. 2010.

Key text

  • Steddon S, Ashman N, Chesser A, et al. Oxford Handbook of nephrology and hypertension. Oxford University Press, 2007, Oxford.
  • Ronco C, Bellomo R, Kellum J. Acute kidney injury. Basal, Karger, 2007.


  • The National Confidential Enquiry into Patient Outcomes and Death. Adding insult to injury. 2009.

This report investigated the management of patients who died as result of AKI and highlighted the failings in their clinical care. The report inclu­ded recommendations for the early diagnosis, prevention and management of AKI.

KDIGO is a global foundation dedicated to improving the care and outcomes of kidney disease patients. It has five global clinical practice guidelines in nephrology under development.

  • Visit our GP Curriculum Centre for hundreds of articles linked to key topics in the RCGP curriculum.

Reflect on this article and add notes to your CPD Organiser on MIMS Learning

CPD IMPACT: Earn more credits

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Review all of your patients with CKD and identify risk factors for developing AKI.
  • Make a leaflet and poster highlighting high-risk drugs which should be avoided in CKD patients.
  • Hold a clinical meeting to discuss AKI, how it presents and how it should be managed in practice.

1. Bellomo R, Ronco C, Kellum JA, et al. Crit Care 2004; 8: R204–12.

2. Mehta RL, Kellum JA, Shah SV et al. Crit Care 2007; 11: R31.

3. Feest TG, Round A, Hamad S. BMJ 1993; 306: 481–3.

4. Stevens PE, Tamimi NA, Al Hasani MK, et al. QJM 2001; 94: 533–40.

5. Chertow GM, Burdick E, Honour M, et al. J Am Soc Nephrol 2005; 16: 3365–70.

6. Goldberg R, Dennen P. Adv Chronic Kidney Dis 2008; 15(3): 297–307.

7.Coca SG, Yusuf B, Shlipak MG, et al. Am J Kidney Dis 2009; 53: 961–73.

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