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Acute Kidney Injury

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Overview

Previously known as acute renal failure, acute kidney injury (AKI) describes a spectrum of disorders leading to reduced kidney function over hours to days. An AKI can lead to a failure to maintain fluid, electrolyte, or acid-base homeostasis.

An AKI may occur in patients with previously intact renal function or in patients with pre-existing renal disease (known as acute-on-chronic kidney disease).

Its causes can be divided into pre-renal, renal (intrinsic), and post-renal causes.

Epidemiology

  • AKI is very common in acute illness (e.g. sepsis)
  • The incidence of AKI is rising, which may be due to increasing numbers of elderly or at-risk people with multiple comorbidities, and better detection of AKI

Summary (Key Facts)

Overview

  • Oliguria is defined as a urine output less than 0.5 mL/kg/hr

Causes

  • Pre-renal causes include causes that decrease blood flow to the kidney such as:
    • Hypovolaemia (e.g. dehydration), decreased cardiac output (e.g. heart failure)
    • Drugs that cause renal hypoperfusion (e.g. ACE inhibitors, angiotensin II receptor blockers and diuretics)
  • Renal (intrinsic) causes include causes that directly damage renal tissue itself including:
  • Post-renal causes include causes of obstruction to urine outflow such as:

Initial tests

  • Urea and electrolytes (U&Es) – used to confirm a diagnosis of AKI:
    • Urea, creatinine, and potassium may be elevated
    • Creatinine tends to rise around 24 hours following the start of an AKI
  • Urea:creatinine ratio – can help determine if the cause is pre-renal, renal, or post-renal:
    • Calculated by dividing urea by creatinine, ensuring the units are the same
      • A ratio of >110:1 suggests a pre-renal cause
        • A disproportionate increase in urea suggests hypoperfusion
      • A ratio of <40:1 suggests a renal cause
        • Suggests decreased urea absorption due to intrinsic renal damage
      • A ratio of 40-110:1 suggests a normal result or post-renal cause
        • This suggests urea reabsorption is within normal limits
  • Urinalysis – dipstick testing for blood, protein, leukocytes, nitrites, and glucose should be performed in all patients with AKI:
    • May give clues to the underlying cause
    • All patients with suspected AKI should have urinalysis testing
  • Renal ultrasound:
    • If there is an AKI with no identifiable cause or those at risk of urinary tract obstruction
    • Performed within 24 hours of assessment

Other tests

  • Full blood count (FBC):
    • Leukocytosis may suggest infection (e.g. sepsis)
    • Eosinophilia may suggest acute interstitial nephritis
    • Thrombocytopenia with or without anaemia may suggest thrombotic microangiopathy (e.g. haemolytic uraemic syndrome) – if present, request a blood film and lactate dehydrogenase
  • Blood cultures – if sepsis is suspected
  • Liver function tests – if hepatorenal syndrome is suspected
  • Creatine kinase – if rhabdomyolysis is suspected
  • C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) – non-specific markers of inflammation
  • Calcium and phosphate – may be deranged in myeloma
  • Immunological tests (e.g. autoantibodies)
  • Virology tests – including hepatitis B and C, and HIV
  • Kidney biopsy – may be considered in some scenarios

Diagnosis

An AKI can be diagnosed if any of the following apply:

  • A rise in creatinine of ≥26 µmol/L in 48 hours or
  • A ≥50% rise in creatinine over 7 days or
  • A fall in urine output to <0.5 mL/kg/hr for >6 hours in adults or 8 hours in children or
  • A ≥25% fall in the estimated glomerular filtration rate (eGFR) in both children and young people over 7 days

Staging criteria

  • Stage 1 AKI:
    • An increase in creatinine to 1.5-1.9 times the baseline or
    • A reduction in urine output to <0.5 mL/kg/hr for ≥6 hours
  • Stage 2 AKI:
    • An increase in creatinine to 2.0-2.9 times the baseline or
    • A reduction in urine output to <0.5 mL/kg/hr for ≥12 hours
  • Stage 3 AKI:
    • An increase in creatinine to ≥3.0 times the baseline or
    • A reduction in urine output to <0.5 mL/kg/hr for ≥24 hours

AKI vs. CKD

Features supporting CKD:

  • Anaemia – due to anaemia of chronic disease and reduced erythropoietin release from the kidneys
  • Hypocalcaemia – due to reduced activation of vitamin D, which takes place in the kidneys
  • Increased phosphate also leads to the deposition of calcium in calcium phosphate, which is insoluble, and therefore removed from the circulation
  • Hyperphosphataemia – dysfunction of the kidneys leads to decreased phosphate excretion
  • Small kidneys on ultrasound – this may not always be seen:

Features supporting AKI:

  • Acutely unwell patients or hypovolaemia make CKD less likely and AKI more likely.

Management

STOP AKI:

  • Sepsis – screen for sepsis and treat
  • Toxins – stop and identify any nephrotoxic drugs/agents
  • Optimise blood pressure – correct hypovolaemia, withhold drugs that contribute to AKI, consider critical care escalation for vasopressors if patients are still hypotensive despite fluid resuscitation
  • Prevent harm – identify and treat reversible causes, treat complications, and review medications

Drugs in AKI

Drugs that are usually safe in AKI:

  • Paracetamol
  • Aspirin (at a cardioprotective dose)
  • Clopidogrel
  • Warfarin
  • Statins
  • Beta-blockers

Drugs that should be stopped as they can worsen an AKI:

  • NSAIDs (except low-dose cardioprotective aspirin)
  • ACE inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Aminoglycosides (e.g. gentamicin)
  • Diuretics

Drugs that may be stopped as an AKI can increase toxicity, but they do not usually worsen the AKI itself:

  • Metformin – due to increased risk of lactic acidosis
  • Lithium – due to increased risk of lithium toxicity
  • Digoxin – due to increased risk of digoxin toxicity

Indications for haemodialysis

  • Remembered with AEIOU:
  • Acidosis – Electrolytes (hyperkalaemia)
  • Ingestion or overdose of medications/drugs
  • Overload of fluid causing heart failure and pulmonary oedema
  • Uraemia leading to pericarditis or encephalopathy

Hyperkalaemia

Hyperkalaemia:

  • Mild (K+ of 5.5-5.9 mmol/L):
    • Identify and treat underlying cause
    • Consider cation exchange resin to remove K+ from body (e.g. calcium resonium)
  • Moderate (K+ of 6.0-6.4 mmol/L):
    • Perform ECG. If changes are present, treat as severe hyperkalaemia
    • If no ECG changes present:
      • IV insulin and glucose infusion – moves potassium intracellularly
  • Consider adjunct nebulised salbutamol – avoid if tachyarrhythmia present
    • Severe (K+ ≥6.5 mmol/L):
    • Seek advice from nephrology/intensive care and monitor in a high-dependency area
    • Immediate IV calcium gluconate or IV calcium chloride – for cardioprotection and prevents arrhythmia
    • Seek senior advice if the ECG does not normalise after one dose

Acidosis

Pulmonary oedema

  • Sit the patient upright – allows for better gas exchange as fluids settle in the lung bases
  • Give high-flow oxygen at 15 L/min via a reservoir mask
  • Consider IV glyceryl trinitrate if systolic blood pressure is >90 mmHg and there is no valvular heart disease
  • Loop diuretics may be considered by specialists if the patient is haemodynamically stable and not dehydrated
  • Seek senior support
  • Refer for renal replacement therapy

Uraemic encephalopathy or pericarditis

  • Refer for renal replacement therapy

Pre-renal causes

These are causes that decrease blood flow to the kidney. Pre-renal causes of AKI act in a similar way to reduced blood flow to the heart in myocardial ischaemia. Some causes include:

  • Hypovolaemia:
    • Dehydration
    • Haemorrhage
    • Gastrointestinal fluid losses (e.g. vomiting/diarrhoea or increased ostomy output)
    • Renal fluid losses
    • Burns
  • Decreased cardiac output:
    • Heart failure
    • Arrhythmia
  • Drugs causing renal hypoperfusion:
    • Angiotensin-converting enzyme (ACE) inhibitors
    • Angiotensin II receptor blockers (ARBs)
    • NSAIDs or selective cyclo-oxygenase-2 (COX-2) inhibitors
    • Diuretics
  • Other causes of renal hypoperfusion:

Renal (intrinsic) causes

These are causes where the disease process directly damages the kidney tissue itself. Some causes include:

  • Toxins and drugs:
    • Antibiotics (e.g. aminoglycosides such as gentamicin)
    • Radiocontrast media, particularly iodinated contrast
    • Chemotherapy drugs (e.g. tacrolimus)
  • Vascular disease:
  • Tubular disease:
    • Acute tubular necrosis
    • Rhabdomyolysis
    • Multiple myeloma
  • Interstitial disease:
    • Acute interstitial nephritis
    • Lymphoma infiltration
  • Glomerular diseases:
  • Other:
    • Eclampsia

Post-renal causes

These are causes where there is a mechanical obstruction of the urinary outflow tract (usually bladder outlet obstruction. It is important to note that the unaffected kidney may compensate for unilateral masses affecting kidney outflow. Causes include:

Risk factors

  • Aged ≥65 years
  • History of AKI
  • Chronic kidney disease (CKD)
  • Chronic conditions including heart failure, liver disease, and diabetes mellitus
  • Hypovolaemia
  • Disability leading to reliance on a carer, which may limit fluid intake
  • Sepsis
  • Oliguria (urine output <0.5 mL/kg/hr)
  • Nephrotoxic drug use within the past week
  • Exposure to iodinated contrast agents within the past week
  • Cancer and chemotherapy
  • Immunocompromised patients (e.g. HIV)

Presentation

The presentation depends on the underlying cause. Many patients may not experience clear symptoms, however, as urea and electrolytes become more deranged in AKI, symptoms may emerge such as:

  • Decreasing urine output with or without increasing serum creatinine
  • Nausea and vomiting
  • Arrhythmia – if hyperkalaemia develops
  • Dehydration
  • Confusion
  • Features of Uraemia

Investigations

Initial tests

Key investigations involve:

  • Urea and electrolytes (U&Es) – used to confirm a diagnosis of AKI:
    • Urea, creatinine, and potassium may be elevated
    • Creatinine tends to rise around 24 hours following the start of an AKI
  • Urea:creatinine ratio – can help determine if the cause is pre-renal, renal, or post-renal:
    • Calculated by dividing urea by creatinine, ensuring the units are the same
      • A ratio of >110:1 suggests a pre-renal cause
        • A disproportionate increase in urea suggests hypoperfusion
    • A ratio of <40:1 suggests a renal cause
      • Suggests decreased urea absorption due to intrinsic renal damage
    • A ratio of 40-110:1 suggests a normal result or post-renal cause
      • This suggests urea reabsorption is within normal limits
  • Urinalysis – dipstick testing for blood, protein, leukocytes, nitrites, and glucose should be performed in all patients with AKI:
    • May give clues to the underlying cause
  • Renal ultrasound:
    • If there is an AKI with no identifiable cause or those at risk of urinary tract obstruction
    • Performed within 24 hours of assessment

Other tests

Other tests can be performed to help with identifying the underlying cause:

  • Full blood count (FBC):
    • Leukocytosis may suggest infection (e.g. sepsis)
    • Eosinophilia may suggest acute interstitial nephritis
    • Thrombocytopenia with or without anaemia may suggest thrombotic microangiopathy (e.g. haemolytic uraemic syndrome) – if present, request a blood film and lactate dehydrogenase
  • Blood cultures – if sepsis is suspected
  • Liver function tests – if hepatorenal syndrome is suspected
  • Creatine kinase – if rhabdomyolysis is suspected
  • C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) – non-specific markers of inflammation
  • Calcium and phosphate – may be deranged in myeloma
  • Immunological tests:
    • Tests for multiple myeloma (serum immunoglobulins, serum protein electrophoresis, urine protein electrophoresis)
    • Anti-nuclear antibody (ANA) – screening test for autoimmune disease
    • Complement concentrations – may be low in some autoimmune diseases
    • Anti-glomerular basement membrane (anti-GBM) antibodies – for anti-GBM disease (Goodpasture’s syndrome)
    • Antineutrophil cytoplasmic antibody (ANCA) – associated with systemic vasculitis
  • Virology tests – including hepatitis B and C, and HIV
  • Kidney biopsy – may be considered in some scenarios

Differentiate Acute Kidney Injury and Chronic Kidney Disease (CKD)

It is essential to differentiate between AKI and CKD, as their management steps vary. This may be difficult if there are no baseline measurements of kidney function available. Some features that support the likelihood of CKD include:

  • Anaemia – due to anaemia of chronic disease and reduced erythropoietin release from the kidneys
  • Hypocalcaemia – due to reduced activation of vitamin D, which takes place in the kidneys
    • Increased phosphate also leads to the deposition of calcium in calcium phosphate, which is insoluble, and therefore removed from the circulation
  • Hyperphosphataemia – dysfunction of the kidneys leads to decreased phosphate excretion
  • Small kidneys on ultrasound – this may not always be seen:
    • E.g. in polycystic kidney disease, a cause of CKD, the kidneys may be enlarged

Acutely unwell patients or hypovolaemia make CKD less likely and AKI more likely.

Diagnostic Criteria and Staging

Diagnostic criteria (NICE)

An AKI can be diagnosed if any of the following apply:

  • A rise in creatinine of ≥26 µmol/L in 48 hours or
  • A ≥50% rise in creatinine over 7 days or
  • A fall in urine output to <0.5 mL/kg/hr for >6 hours in adults or 8 hours in children or
  • A ≥25% fall in the estimated glomerular filtration rate (eGFR) in both children and young people over 7 days

Staging criteria (Kidney Disease: Improving Global Outcomes (KDIGO))

AKI can be staged as:

  • Stage 1 AKI:
    • An increase in creatinine to 1.5-1.9 times the baseline or
    • An increase in creatinine by ≥26.5 µmol/L or
    • A reduction in urine output to <0.5 mL/kg/hr for ≥6 hours
  • Stage 2 AKI:
    • An increase in creatinine to 2.0-2.9 times the baseline or
    • A reduction in urine output to <0.5 mL/kg/hr for ≥12 hours
  • Stage 3 AKI:
    • An increase in creatinine to ≥3.0 times the baseline or
    • An increase in creatinine to ≥353.6 µmol/L or
    • A reduction in urine output to <0.5 mL/kg/hr for ≥24 hours or
    • The initiation of kidney replacement therapy (dialysis) or
    • In patients <18 years, a decrease in eGFR to <35 mL/min/1.73 m2

Management

Overview

Management is mainly supportive and depends on the underlying cause. The ‘STOP AKI’ acronym is useful in initial management:

  • Sepsis – screen for sepsis and initiate sepsis six if appropriate:
    • ‘BUFALO’ – blood cultures, urine output and U&Es, IV fluids, IV antibiotics, lactate and haemoglobin, high-flow oxygen)
  • Toxins – identify and stop any nephrotoxins
    • E.g. aminoglycosides (e.g. gentamicin), NSAIDs, and iodinated contrast media
  • Optimise blood pressure:
    • If hypovolaemia: immediate IV bolus of a crystalloid, unless hyperkalaemia is present, then use normal saline
    • Withhold drugs that can contribute to AKI
    • Escalate to critical care for consideration of vasopressors if the patient is still hypotensive despite adequate fluid resuscitation
  • Prevent harm:
    • Identify and treat reversible causes (e.g. urinary tract obstruction which may require a bladder catheter)
    • Treat life-threatening complications (e.g. hyperkalaemia and acidosis)
    • Review all medications and the patient’s fluid management plan and adjust accordingly

Drugs in Acute Kidney Injury

Some common drugs may be safe to continue or require stopping:

Drugs that are usually safe in AKI:

  • Paracetamol
  • Aspirin (at a cardioprotective dose)
  • Clopidogrel
  • Warfarin
  • Statins

Drugs that should be stopped as they can worsen an AKI:

  • NSAIDs (except low-dose cardioprotective aspirin)
  • ACE inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Aminoglycosides (e.g. gentamicin)
  • Diuretics

Drugs that may be stopped as an AKI can increase toxicity, but they do not usually worsen the AKI itself:

  • Metformin – due to increased risk of lactic acidosis
  • Lithium – due to increased risk of lithium toxicity
  • Digoxin – due to increased risk of digoxin toxicity

Urological obstruction

Refer to a urologist if any of the following apply, as urological obstruction may need relieving (e.g. via nephrostomy or stenting):

  • Pyelonephritis
  • An obstructed kidney
  • Bilateral upper urinary tract obstruction
  • Complications of an AKI due to urological obstruction

Renal replacement therapy (RRT, haemodialysis)

Refer to nephrology or critical care if they quality for RRT, which includes any of the following that is not responding to medical management (can be remembered using AEIOU):

  • Acidosis
  • Electrolytes (hyperkalaemia)
  • Ingestion or overdose of medications/drugs
  • Overload of fluid causing heart failure and pulmonary oedema
  • Uraemia leading to pericarditis or encephalopathy

Referral to nephrology

  • Patients with an eGFR of 30 ml/min/1.73 m2 or less should be referred to a nephrologist.
  • Discussing the management of AKI with a nephrologist if any of the following apply:
  • A possible diagnosis that may require specialist treatment (e.g. vasculitis, glomerulonephritis, multiple myeloma, or tubulointerstitial nephritis)
  • An AKI with no clear cause
  • An inadequate response to treatment
  • The presence of complications associated with AKI
  • Stage 3 AKI
  • Patients with a renal transplant
  • Patients with CKD

Complications

Hyperkalaemia

Treatment depends on severity. Perform an ECG in all patients with hyperkalaemia:

  • Mild hyperkalaemia (K+ of 5.5-5.9 mmol/L):
    • Identify and treat underlying causes such as medication
    • Consider cation-exchange resin (e.g. calcium resonium) to remove K+ from the body
  • Moderate hyperkalaemia (K+ 6.0-6.4 mmol/L):
    • ECG changes present – manage as severe hyperkalaemia
    • If no ECG changes are present:
      • IV insulin and glucose infusion – moves potassium intracellularly
      • Consider adjunct nebulised salbutamol – avoid if tachyarrhythmia present
  • Severe hyperkalaemia (K+ ≥6.5 mmol/L):
    • ECG changes present – seek advice from nephrology/intensive care and monitor in a high-dependency area
    • Immediate IV calcium gluconate or IV calcium chloride – for cardioprotection and prevents arrhythmia
    • Seek senior advice if the ECG does not normalise after one dose

Acidosis

  • Seek expert advice as IV sodium bicarbonate may be needed due to the risk of volume overload and/or hypernatraemia
  • IV sodium bicarbonate is indicated if the pH <7.20 (severe acidosis)
  • Consider referring to intensive care
  • Refer for RRT as mentioned above

Pulmonary oedema

This may occur due to the underlying cause of AKI (e.g. heart failure, renal artery stenosis) or due to excessive IV fluid resuscitation:

  • Sit the patient upright – allows for better gas exchange as fluids settle in the lung bases
  • Give high-flow oxygen at 15 L/min via a reservoir mask
  • Consider IV glyceryl trinitrate if systolic blood pressure is >90 mmHg and there is no valvular heart disease
  • Loop diuretics may be considered by specialists if the patient is haemodynamically stable and not dehydrated
  • Seek senior support
  • Refer for RRT as mentioned above

Uraemic encephalopathy or pericarditis

Prognosis

  • The prognosis depends on the clinical setting, underlying causes, and comorbidities
  • Early detection of AKI is associated with better outcomes
  • The risk of mortality increases with the stage of AKI
  • Patients who have had an AKI are at increased risk of developing CKD

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