Investigations
1st investigations to order
basic metabolic profile (including urea and creatinine and liver function tests)
Test
Creatinine for AKI diagnosis
AKI is often asymptomatic so is easily missed.[75]
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][10][75]
Age ≥65 years (frail older people are at particular increased risk).[48][82]
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:
Any nephrotoxin (e.g., non-steroidal anti-inflammatory drug [NSAID], aminoglycoside antibiotic)
Iodinated contrast agent
Renin-angiotensin-system modifying agent (e.g., ACE inhibitor/angiotensin-II receptor antagonist) and/or diuretic, especially if hypovolaemic or hypotensive.
Symptoms or history of urological obstruction
Suspected or confirmed sepsis
Hypovolaemia (with or without hypotension) - may be related to dehydration or over-diuresis[10]
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 identified based on an acute rise in serum creatinine and/or a sustained reduction in urine output.[1]
Baseline serum creatinine corresponds to the level when a patient was most recently in a clinically stable condition; often this is considered the lowest creatinine reading within the last 3 months (the UK Royal College of Physicians also recommends using the lowest reading within the last 7 days, if available).[75]
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 thata 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.[14]
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:[10][75]
Hypocalcaemia
Hyperphosphataemia and hyperparathyroidism
Anaemia
Small kidneys on ultrasound (sometimes scarred) - suggestive of advanced CKD.
If the patient is acutely unwell or hypovolaemic, this points towards AKI.[10]
These features can be remembered using the ABCS mnemonic: Anaemia, Bone chemistry [abnormal], Clinical tolerance of uraemia, Small kidneys.
Repeat blood testing along with reference to historical creatinine values is the key to confirming or ruling out AKI.
Remember that pre-existing CKD is a risk factor for AKI.
Practical tip
Beware false positive rises in creatinine, for example:[1][10]
Recent use of trimethoprim can lead to a rise in serum creatinine that does not reflect any change in glomerular filtration rate (most commonly in patients with pre-existing CKD).
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][14]
A higher stage of AKI is associated with a greater risk of death as well as increased likelihood of needing renal replacement therapy (RRT).[14]
For any hospital inpatient with AKI, ensure daily monitoring of urea and electrolytes until the AKI has resolved, as indicated by:[14]
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. | |
More info: AKI stage and mortality
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.[10][11]
Even relatively minor changes in serum creatinine levels are associated with a significant increase in mortality.[75]
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.
LFTs
Often abnormal in clinical scenarios consistent with presence of AKI (e.g., circulatory failure causing pre-renal AKI and ischaemic hepatitis, infections, drug toxicity); concomitant AKI and liver disease confers a poor prognosis. Aids diagnosis of hepatorenal syndrome.[75]
Result
acutely elevated serum creatinine, high serum potassium, metabolic acidosis
confirm AKI if there is:[1][3][4]
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
serum potassium
Test
Ensure close monitoring of serum potassium.[75][94]
Hyperkalaemia is a common complication of AKI.
Urgent treatment is required if potassium >6.0 mmol/L and/or ECG changes are seen.
Result
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
FBC
Test
Leukocytosis may suggest infection.
High or low WBC can occur with sepsis.
If platelets are low, request a blood film and lactate dehydrogenase:[75]
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, or may occur in AKI secondary to the underlying cause (e.g., gastrointestinal haemorrhage).
Result
anaemia, leukocytosis, thrombocytopenia
bicarbonate
Test
Request bicarbonate if it is not part of the standard panel.[75][81][82]
Alternatively, if previously taken bloods indicate AKI and bicarbonate was not included, request a venous blood gas.
Venous blood gases can help with further evaluation of acidosis.
Result
low bicarbonate suggests metabolic acidosis
C-reactive protein
blood culture
urinalysis
Test
Perform urine dipstick testing for specific gravity, blood, protein, leucocytes, nitrites, and glucose as soon as AKI is suspected or confirmed.[3][75]
Use a clean-catch specimen.
Consider the possibility of intrinsic AKI especially 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][10][81]
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).
Result
RBCs, WBCs, cellular casts, proteinuria, positive nitrite, and leukocyte esterase
urine culture
Test
Send urine culture if clinical features of urinary tract infection are present and/or urinalysis is positive for blood, protein, leukocytes, or nitrites.[81]
Result
bacterial growth with antibiotic sensitivity
urine output monitoring
Test
Start urine output monitoring in any patient with AKI (hourly if catheterised, 4-hourly if not).[81]
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.[81]
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.
Result
confirm 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
fluid challenge
Test
A good response to a fluid challenge supports a diagnosis of pre-kidney AKI.
Result
kidney function improves rapidly in pre-kidney AKI
venous blood gases
Test
Can be requested to assess acid/base status.
An anion gap acidosis is seen in AKI due to impaired excretion of non-volatile acids.
Result
an anion gap acidosis occurs in a number of different scenarios
CXR
Test
Request a chest x-ray.[82] 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.
Result
may show signs of infection, fluid, cardiomegaly, or haemorrhage
ECG
Test
An ECG is important to assess for hyperkalaemia.
Hyperkalaemia is a common complication of AKI.
Result
ECG changes associated with hyperkalaemia: peaked T waves, increased PR interval, widened QRS, atrial arrest, and deterioration to a sine wave pattern
Investigations to consider
renal tract ultrasound
Test
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][14][81]
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][14]
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][81]
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).[14]
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.[75][14]
Be aware that an ultrasound finding consistent with CKD does not exclude the possibility of AKI on a background of CKD.[14]
Result
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
may demonstrate small (sometimes scarred) kidneys consistent with advanced CKD (such changes are unlikely to be seen in less severe CKD)
abdominal CT or MRI scan
Test
Consider requesting a CT or MRI If obstruction is suggested on ultrasound (e.g., possible masses or stones).[14]
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).
Result
image of mass or stone may be present
nuclear renal flow scan
Test
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.[14]
The scan is performed before and after a dose of loop diuretic.
Result
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
Test
Urine osmolality is rarely requested.[14]
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][98]
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.[98]
Result
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
urine sodium concentration
Test
In pre-kidney AKI the urinary sodium is typically low.[14]
This is dependent on preserved tubule function.
Urinary sodium is raised in intrinsic AKI when there is tubule damage, or in response to diuretics.
Result
urinary sodium <20 mmol/L suggests avid sodium retention in pre-kidney AKI
fractional excretion of sodium/urea
Test
Consider requesting urine electrolytes to measure fractional excretion of sodium or urea - but beware the potential pitfalls.[14]
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.
Low fractional excretion of sodium (FENa) 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 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.
The fractional excretion of urea is calculated as: 100% X (urine urea x plasma creatinine)/(plasma urea x urine creatinine).
Result
a fractional excretion of sodium (FENa) of <1% supports pre-kidney AKI, as long as tubular function remains intact [ Fractional Excretion of Sodium (SI units) Opens in new window ]
invalid if the patient has received diuretics
typically <0.2% in hepatorenal syndrome[97]
a fractional excretion of urea of <35% supports a diagnosis of pre-kidney AKI
urinary eosinophil count
Test
Urinary eosinophil counts may be of some use in patients with pyuria.[14][100]
The test is dependent on the expertise of the microscopist.
Eosinophiluria is not specific to interstitial nephritis and may be seen with atheroembolic disease as well.
Some guidelines (e.g., American Association for Clinical Chemistry) advise against the routine use of urinary eosinophils in the evaluation of AKI.[97]
serum creatine kinase
ANA (anti-nuclear antibodies)
anti-dsDNA
complement (C3, C4, CH50)
anti-glomerular basement membrane antibody
anti-neutrophil cytoplasmic antibodies (ANCA)
acute hepatitis profile
Test
Positive serology in active hepatitis B or C is associated with kidney conditions such as membranoproliferative glomerulonephritis and cryoglobulinaemia.
Result
positive or negative serology
HIV serology
Test
Relevant with regard to HIV-associated nephropathy and nephrotoxicity of some of the medications used to manage HIV.
Result
positive or negative
cryoglobulins
Test
The presence of cryoglobulins in a patient with AKI supports a diagnosis of cryoglobulin-associated glomerulonephritis.
Result
positive or negative serology
anti-streptolysin-O antibody
Test
An elevated titre supports but is not diagnostic of post-infectious glomerulonephritis as the cause of AKI.[14]
Result
normal or elevated
serum/urine electrophoresis
Test
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.[10][81][82]
Serum electrophoresis will show a paraprotein (monoclonal immunoglobulin), with monoclonal excess of light chains in serum or urine.[103]
Result
paraprotein identified on serum electrophoresis
serum free light chains (sFLC) or urinary Bence Jones detected
cystoscopy
Test
May be requested to identify cause of obstruction (e.g., ureteric stenosis, bladder tumour).
Result
direct visualisation and treatment of ureteral stenosis if present
kidney biopsy
Test
Kidney biopsy may be required to further investigate positive serological studies and confirm the cause of AKI.[14]
Result
changes associated with rarer forms of intrinsic AKI
Emerging tests
novel serum and urinary biomarkers
Use of this content is subject to our disclaimer