Investigations
Creatinine for AKI diagnosis
AKI is often asymptomatic so is easily missed.[62]
An acutely rising creatinine may be the only sign.
Rises in creatinine are delayed for approximately 24 hours following kidney injury.
Measure serum creatinine to check for AKI whenever an acutely ill patient meets one or more of the following criteria:[3][9][62]
Age ≥65 years
History of any one or more of chronic kidney disease (CKD), heart failure, liver disease, diabetes, dementia
Previous AKI episode
Exposure within the previous week to:
Iodinated contrast agent
Any other nephrotoxin (e.g., non-steroidal anti-inflammatory drug [NSAID], aminoglycoside antibiotic)
Renin-angiotensin-system modifying agent (e.g., ACE inhibitor/angiotensin-II receptor antagonist)
Diuretic.
Symptoms or history of urological obstruction
Suspected or confirmed sepsis
Hypovolaemia (with or without hypotension) - may be related to dehydration or over-diuresis[9]
Hypotension (SBP <90 mmHg or a fall of >40mmHg from baseline BP)
Oliguria (urine output <0.5ml/kg/hour)
Acute rise in early warning score (e.g., NEWS2 >5).
AKI is diagnosed based on an acute rise in serum creatinine and/or a sustained reduction in urine output.[1]
Baseline serum creatinine is best considered clinically as the lowest value over the previous 3 months.[62]
If no recent creatinine value is available, provided the patient does not have CKD it is reasonable to assume that creatinine levels will have been stable for some time, so that a measurement from 6 months or even 1 year ago can be used as the baseline.[1]
If there is no previous serum creatinine within the previous year, and AKI is suspected, consider repeating the creatinine within 12 hours - and certainly within 24 hours.[13]
Practical tip
It is important to differentiate AKI from a progression of CKD at initial presentation.
This can be difficult if there are no recent comparison creatinine values. The clinical context will be important in helping you assess whether a rise in serum creatinine has been acute or occurred over a longer period.
Features that favour a diagnosis of CKD (although do not exclude AKI) include:[9][62]
Hypocalcaemia
Hyperphosphataemia
Anaemia
Small kidneys on ultrasound (sometimes scarred) - suggestive of advanced CKD.
If the patient is acutely unwell or hypovolaemic, this points towards AKI.[9]
Remember that pre-existing CKD is a risk factor for AKI.
Repeat blood testing along with reference to historical creatinine values is the key to confirming or ruling out AKI.
Practical tip
Beware false positive rises in creatinine, for example:[1][9]
Recent use of trimethoprim can lead to a rise in serum creatinine that does not reflect any change in glomerular filtration rate.
Serum creatinine falls during pregnancy so a rise in creatinine after recent delivery may be a false positive.
Creatinine for AKI staging
Stage the AKI using whichever one of serum creatinine or urine output gives the higher stage.[1][13]
A higher stage of AKI is associated with a greater risk of death as well as increased likelihood of needing renal replacement therapy (RRT).[13]
For any hospital inpatient with AKI, ensure daily monitoring of urea and electrolyes until the AKI has resolved, as indicated by:[13]
A return to actual or presumed baseline kidney function
or
The establishment of steady state kidney function.
Serum creatinine (SCr) criteria* | |
|---|---|
Stage 1 |
|
Stage 2 |
|
Stage 3 |
|
*Baseline SCr is the lowest level in the last 7 days or, if not available, the lowest within the previous 3 months. | |
Practical tip
Even relatively minor changes in serum creatinine levels are associated with a significant increase in mortality.[62]
In a person with normal kidney function, a rise of creatinine above the normal range reflects a loss of more than 50% of function and a significant loss in kidney reserve.
Mortality rises sharply with increasing stage of AKI
AKI during hospital admission is associated with an overall mortality of greater than 20%, whereas stage 3 AKI is associated with >35% mortality.[3][9][68]
A comparison of the RIFLE, AKIN, and KDIGO staging systems found they were all good predictors of mortality.[71] Whichever system was used, the key message was that mortality increases with severity as determined by rising serum creatinine.
One study of more than 20,000 patients showed a nearly linear increase in in-hospital mortality with increasing RIFLE stage.[72]
Patients at Risk (R) had triple the mortality rate of patients without AKI.
Patients with Injury (I) had close to twice the mortality of R.
Patients with Failure (F) had 10 times the mortality rate of inpatients without AKI.
The RIFLE and KDIGO criteria map to each other approximately as:
R = KDIGO stage 1
I = KDIGO stage 2
F = KDIGO stage 3
KDIGO diagnostic and staging criteria
The international KDIGO guideline group harmonised the previous definitions and staging criteria for AKI to produce a widely accepted consensus.[1]
Prior to the 2012 KDIGO definitions, there were a large number of different definitions of AKI.
In one study of 50,000 patients that compared the incidence of AKI using the RIFLE, AKIN, and KDIGO criteria, 11.6% of hospitalised patients were diagnosed as having AKI with the KDIGO criteria and 11.0% with the RIFLE criteria, whereas only 4.8% were classified as having AKI under the AKIN criteria.[74]
A comparison of the RIFLE definition with the modified AKIN definition demonstrated that there were subsets of patients defined as having AKI by each definition that were not detected by the other.[75]
The RIFLE criteria failed to detect 9% of cases that were detected by AKIN criteria.
The AKIN criteria missed 26.9% of cases detected by RIFLE.
The advent of agreed AKI definitions has allowed a better understanding of the incidence and outcomes of patients with AKI. This has in turn stimulated the development of new potential therapeutic interventions for AKI.[13]
LFTs
Will aid diagnosis of hepatorenal syndrome.[62]
acutely elevated serum creatinine, high serum potassium, metabolic acidosis
confirm the diagnosis of AKI if there is:[4][1][3]
a rise in serum creatinine of ≥26 micromol/L (≥0.3 mg/dL) within 48 hours
OR
a rise in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the past 7 days
LFTs will be deranged in hepatorenal syndrome
Ensure close monitoring of serum potassium.[62][80]
Hyperkalaemia is a common complication of AKI.
Urgent treatment is required if potassium >6.0 mmol/L and/or ECG changes are seen.
elevated in hyperkalaemia
5.5 to 5.9 mmol/L indicates mild hyperkalaemia
6.0 to 6.4 mmol/L indicates moderate hyperkalaemia
≥6.5 mmol/L indicates severe hyperkalaemia
Leukocytosis may suggest infection.
High or low WBC can occur with sepsis.
If platelets are low, request a blood film and lactate dehydrogenase:[62]
Use to check for rare disorders such as haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, cryoglobulinaemia.[1]
Anaemia can occur in AKI secondary to haemolytic uraemic syndrome, myeloma, or vasculitis.
anaemia, leukocytosis, thrombocytopenia
Perform urine dipstick testing for specific gravity, blood, protein, leucocytes, nitrites, and glucose as soon as AKI is suspected or diagnosed.[3][62]
Use a clean-catch specimen.
Consider the possibility of intrinsic AKI if urinalysis is positive for both blood and protein in the absence of an obvious alternative cause (e.g., urinary tract infection [UTI] or trauma from urinary catheterisation).[3][9][64]
Proteinuria together with haematuria may indicate an active urinary sediment due to glomerular disease.
Patients with glomerular disease typically present with proteinuria and haematuria with hypertension and oedema. An early referral to nephrology is indicated.[3]
However, there remains a wide differential diagnosis for blood and protein on dipstick (e.g., infection, trauma, papillary necrosis).
Careful microscopy of freshly collected, freshly spun urine for the presence of red cell casts can confirm glomerular origin haematuria, but if this is not available then the absence of catheter trauma or UTI should raise concerns about glomerular disease.
Other causes of an active urinary sediment (dysmorphic red cells and red cell casts) include infection, tumours, calculi, venous thrombosis, myoglobinuria (rhabdomyolysis).
RBCs, WBCs, cellular casts, proteinuria, positive nitrite, and leukocyte esterase
Send urine culture if clinical features of urinary tract infection are present and/or urinalysis is positive for blood, protein, leukocytes, or nitrites.[64]
bacterial growth with antibiotic sensitivity
Start urine output monitoring in any patient diagnosed with AKI (hourly if catheterised, 4-hourly if not).[64]
In practice, accurate monitoring can be difficult if the patient is not catheterised.
Routine urinary catheterisation is not appropriate in patients with AKI. Carefully weigh up the benefits against the risks for the individual patient.[64]
Potential benefits:
A sustained fall in urine output is one of the diagnostic criteria for confirming AKI, but urine output is difficult to measure accurately without catheterisation[1]
Urinalysis can be performed on a sample obtained following catheterisation (but be aware that any proteinuria/haematuria might have resulted from catheter-related trauma)
Hourly urinary output monitoring aids assessment of the patient’s response to treatment
Catheterisation can be both diagnostic and therapeutic for bladder neck obstruction.
Potential risks:
Infection
Trauma
Falls risk.
Catheterisation is indicated:
In any case where fluid balance management is crucial
If the patient is too ill to use a bottle or commode
If bladder neck obstruction is suspected and cannot be quickly ruled out by ultrasound.
confirm a diagnosis of AKI if urine output <0.5 ml/kg/hour for at least 6 consecutive hours (at least 8 hours in children/young people)
if catheterisation is considered appropriate:
significant urine volume released after catheter placement points to bladder outlet obstruction
minimal residual urine after catheter placement suggests a non-obstructive cause of AKI or higher level urinary tract obstruction
A good response to a fluid challenge supports a diagnosis of pre-kidney AKI.
kidney function improves rapidly in pre-kidney AKI
Can be requested to assess acid/base status.[64]
An anion gap acidosis is seen in AKI due to impaired excretion of non-volatile acids.
an anion gap acidosis occurs in a number of different scenarios
Request a chest x-ray.[65] It may demonstrate signs of:
Infection
Pulmonary oedema
Haemorrhage (e.g., ANCA-associated vasculitis, Goodpasture syndrome [pulmonary haemorrhage, rapidly progressive glomerulonephritis, and anti-glomerular basement membrane antibodies])
Cardiomegaly.
may show signs of infection, fluid, cardiomegaly, or haemorrhage
An ECG is important to assess for hyperkalaemia.
Hyperkalaemia is a common complication of AKI.
ECG changes associated with hyperkalaemia: peaked T waves, increased PR interval, widened QRS, atrial arrest, and deterioration to a sine wave pattern
If pyonephrosis (an infected/obstructed renal tract) is suspected, ensure the patient has an ultrasound - and if indicated a nephrostomy - within 6 hours due to the risk of septic shock.[3][13][64]
Renal tract ultrasound is not routinely required. Only request it if no obvious cause for the AKI can be found or if obstruction, pyelonephritis, or pyonephrosis is suspected.[3][13]
Ensure the ultrasound is performed within 24 hours if no obvious cause for the AKI can be identified or a urinary tract obstruction is suspected.[3][64]
Ultrasound has high sensitivity (90%-98%) but lower specificity (65%-84%) for diagnosing upper tract obstruction, although this may not be the case in the early stages (first 8 hours).[13]
Repeat the ultrasound after 24 hours if:
There is a high index of suspicion for hydronephrosis (as it may take several hours for this to develop due to initial non-compliance of the pelvi-caliceal system)
The patient has oliguric acute tubular necrosis with superimposed obstruction (because urine is needed to dilate the kidneys).
If prior creatinine values are not available to give a baseline, ultrasound can sometimes be helpful in distinguishing AKI from CKD.[62][13]
Ultrasound may demonstrate small (sometimes scarred) kidneys consistent with advanced CKD (such changes are unlikely to be seen in less severe CKD).
Be aware that an ultrasound finding consistent with CKD does not exclude the possibility of AKI on a background of CKD.[13]
presence of dilated renal calyces suggests obstruction and hydronephrosis
normal kidney size in the setting of AKI and unclear cause and positive serology suggests a rarer cause
reduced corticomedullary differentiation and/or small and scarred kidneys is consistent with CKD
Consider requesting a CT or MRI If obstruction is suggested on ultrasound (e.g., possible masses or stones).[13]
These are not routinely needed - the decision will depend on the degree of obstruction.
Be cautious with intravenous iodinated contrast CT scans in patients with AKI. MRI is preferred (although note that gadolinium may be needed for MRI enhancement).
image of mass or stone may be present
Nuclear renal flow scans can sometimes be useful to evaluate for obstruction in cases of mild hydronephrosis, when the diagnosis of mechanical obstruction is uncertain.[13]
The scan is performed before and after a dose of loop diuretic.
normal scan reveals appropriate kidney perfusion, tracer uptake, and excretion
abnormal scan may demonstrate:
impaired tracer excretion (supportive of acute tubular necrosis)
poor blood flow (supportive of obstruction of blood supply)
normal blood flow and tracer excretion with tracer accumulation in the collecting system (supportive of obstruction of the urine outflow tract)
Urine osmolality is rarely requested.[13]
Urine osmolality is the number of moles of solute per kg of solvent and it depends on tubule response to anti-diuretic hormone (ADH).
High urine osmolality suggests pre-kidney AKI with preservation of tubule function (assuming no recent administration of iodinated contrast).[1][83]
However this should not be interpreted as confirming pre-kidney AKI because intact tubule function (particularly in the early stages) may be seen in various forms of kidney disease (e.g., glomerulonephritis).[1]
Low urine osmolality suggests tubule damage (intrinsic AKI) as urinary concentration is impaired.[83]
urine osmolality >500 mOsm/kg (in the absence of recent administration of iodinated contrast) suggests pre-kidney AKI with preservation of tubule function
urine osmolality <300 mOsm/kg suggests tubule damage
In pre-kidney AKI the urinary sodium is typically low (<20 mmol/L).[13]
This is dependent on preserved tubule function.
Urinary sodium is raised in intrinsic AKI when there is tubule damage, or in response to diuretics.
urinary sodium <20 mmol/L suggests avid sodium retention in pre-kidney AKI
Consider requesting urine electrolytes to measure fractional excretion of sodium or urea - but beware the potential pitfalls.[13]
In principle, calculation of fractional excretion of sodium (FENa) may be helpful in distinguishing pre-kidney from intrinsic AKI. In practice it is rarely performed and results are often difficult to interpret, particularly if loop diuretics have been used within the last 24 hours.
Fractional excretion of sodium (FENa) of <1% suggests pre-kidney AKI but may also be seen in glomerulonephritis, hepatorenal syndrome, some cases of obstruction, and even acute tubular necrosis (if tubular function remains intact).[ Fractional Excretion of Sodium (SI units) ]
Fractional excretion of urea (FEUr) is more useful if the patient has received loop diuretics - although results are also difficult to interpret so the test is rarely performed in clinical practice.
Urea excretion is not significantly affected by diuretics.
A fractional excretion of urea <35% supports a diagnosis of pre-kidney AKI.
The fractional excretion of urea is calculated as: 100% X (urine urea x plasma creatinine)/(plasma urea x urine creatinine).
a fractional excretion of sodium (FENa) of <1% supports pre-kidney AKI, as long as tubular function remains intact
invalid if the patient has received diuretics
a fractional excretion of urea of <35% supports a diagnosis of pre-kidney AKI
may be helpful if the patient has had diuretic exposure
Urinary eosinophil counts may be of some use in patients with pyuria.[85][13][64]
A result above 5% to 7% supports a diagnosis of acute allergic interstitial nephritis but is not diagnostic because of low sensitivity and specificity.[85] The test is dependent on the expertise of the microscopist.
It has a negative predictive value of >90% among patients with AKI and may be useful in excluding the disease process.[86]
Eosinophiluria may be seen with atheroembolic disease as well.
Positive serology in active hepatitis B or C is associated with kidney conditions such as membranoproliferative glomerulonephritis and cryoglobulinaemia.
positive or negative serology
Relevant with regard to HIV-associated nephropathy and nephrotoxicity of some of the medications used to manage HIV.
positive or negative
The presence of cryoglobulins in a patient with AKI supports a diagnosis of cryoglobulin-associated glomerulonephritis.
positive or negative serology
An elevated titre supports but is not diagnostic of post-streptococcal glomerulonephritis as the cause of AKI.[13]
normal or elevated
Myeloma is an important potential cause of AKI and should be considered in a patient aged >40 years who presents with hypercalcaemia, hyperuricaemia, or pathological fracture.[9][64][65]
Serum electrophoresis will show a paraprotein (monoclonal immunoglobulin).
Urine electrophoresis will detect Bence Jones proteins (free light chains) which are not detected on urinalysis.
paraprotein identified on serum electrophoresis
Bence Jones protein detected on urine electrophoresis
May be requested to identify cause of obstruction (e.g., ureteric stenosis, bladder tumour).
direct visualisation and treatment of ureteral stenosis if present
Kidney biopsy may be required to further investigate positive serological studies and confirm the cause of AKI.[13]
changes associated with rarer forms of intrinsic AKI
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