23rd June 2023

Investigation of acute kidney injury

History and examination

A thorough history and examination of the patient will often provide some clues regarding diagnosis. Some example question and examination points to include below:

History

• Pre-renal – increased fluid losses/decreased fluid intake, cardiac issues, infection +/- sepsis.
• Intrinsic – symptoms of systemic connective tissue disease or vasculitis, full drug history, infections, malignancy, periods of prolonged immobility/trauma/limb ischaemia, source of emboli, cardiovascular disease or endovascular intervention
• Post-renal – abdominal pain, haematuria, lower urinary tract symptoms, history of prostatic symptoms

Examination

• Pre-renal – volume status assessment, urine output
• Intrinsic – signs of cardiovascular/peripheral vascular disease, rash, synovitis, mouth ulcers, uveitis, nail changes, epistaxis, pulmonary haemorrhage, signs of connective tissue disease
• Post-renal – palpable bladder, enlarged prostate, abdominal masses

Further investigations

Urinalysis

Urine dip

• If haematoproteinuria is present (and is not related to catheterisation or infection), it may indicate an active glomerulonephritis, vasculitis, or myeloma. It is useful to quantify this further with a urinary protein:creatinine ratio and sending an acute renal screen (see below).
• A ‘bland’ urine dip (i.e. no blood or protein) is more suggestive of a pre-renal AKI, post-renal AKI, interstitial nephritis or atheroembolic disease.
• Myoglobinuria will give a urine dip positive for blood.

Microscopy

• Red cells – cells can be dysmorphic in glomerular sources of bleeding
• White cells – infection, interstitial nephritis, atheroembolic disease
• Casts – various components: red cells (glomerulonephritis); white cells (pyelonephritis, interstitial nephritis); tubular cells (acute tubular necrosis); myoglobin
• Crystals (this requires examination under polarised light)

Urine biochemistry

• This is rarely performed in clinical practice. However, its role in recognising tubular function and differentiating ATN from pre-renal AKI remains a popular exam topic.
• In a pre-renal AKI, the concentrating ability of the renal tubules is maintained, and they act to retain salt, leading to a low urinary sodium or a fractional sodium excretion percentage (ratio of sodium clearance to creatinine clearance) of <1%.
• In ATN, the normal concentrating function of the tubules is lost, and the kidneys will not be able to concentrate urine, leading to a high urinary sodium or a fractional sodium excretion percentage of >2%. This can be affected by diuretics and other clinical states, such as hepatorenal syndrome, which will result in biochemistry in keeping with a pre-renal state.

Bloods

The choice of which investigations to send depends on the clinical scenario. Blood tests may help assess the severity of the AKI and identify serious/life-threatening problems or to identify the underlying cause.

Point of care testing

• A venous or arterial blood gas will quickly identify emergencies such as hyperkalaemia or severe acidosis.

Haematology

• Full blood count – anaemia (check for signs of haemolysis), thrombocytopenia (consider thrombotic microangiopathies (TMA), disseminated intravascular coagulation), raised white cell count (infection/sepsis, interstitial nephritis), bone marrow infiltration.
• Blood film – red cell fragments, thrombocytopenia (consider TMA).

Biochemistry

• Urea and electrolytes
• Liver function tests – raised bilirubin in conditions associated with haemolysis; raised transaminases may be from a muscle rather than a hepatic source, e.g. rhabdomyolysis.
• Bone profile – generally low calcium and high phosphate, but hypercalcaemia can be associated with specific causes, e.g. myeloma.
• Creatine kinase if suspected rhabdomyolysis; consider in cases of extreme exertion, crush injuries, compartment syndrome, and fall with a long lie.
• Others, e.g. CRP, urate

Renal screen

• Antinuclear antibodies (ANA) – specific subtypes include anti-double stranded DNA (anti-dsDNA)
• Anti-neutrophil cytoplasmic antibodies (ANCA) – two main patterns: cytoplasmic (c-ANCA, typically anti-proteinase 3) or perinuclear (p-ANCA, typically anti-myeloperoxidase)
• Anti-glomerular basement membrane antibody (anti-GBM)
• Antistreptolysin O titres – post-streptococcal glomerulonephritis
• Serum and urine protein electrophoresis – myeloma screen
• Immunoglobulins (IgG, IgA, IgM)
• Rheumatoid factor (RhF)– positive in vasculitis associated with rheumatoid arthritis, cryoglobulinaemia
• Complement levels – C3 and C4
• Cryoglobulins – consider only if suspicious clinical syndrome and/or risk factors such as hepatitis C
• Blood-borne virus screen – hepatitis B and C, and HIV can be associated with various forms of renal impairment. It is also useful to know status if haemodialysis is required as patients may need an isolated machine.

Imaging/tissue/other

Imaging

• Imaging of the renal tract (most easily performed via ultrasound) should be performed urgently, primarily for the purpose of ruling out obstruction. Another useful finding is kidney size; chronic renal impairment is suggested by kidneys that appear scarred and shrunken.
• Chest radiograph – consider if there is clinical suspicion of complications such as pulmonary oedema or pulmonary haemorrhage.
• Echocardiogram – to assist fluid status assessment and to assess for complications such as pericardial effusion secondary to uraemia.

Tissue

• A renal biopsy can be considered in cases of intrinsic AKI of unclear cause or where there is suspicion of a condition requiring specific treatment, e.g. a glomerulonephritis, thrombotic microangiopathy or tubulointerstitial nephritis. However, it is important to recognise that this is an invasive procedure, and risks/benefits need to be balanced carefully.

ECG

• An ECG in cases of hyperkalaemia is essential to rule out life-threatening arrythmias.