Acute Kidney Injury

Acute kidney injury (AKI) is a loss in renal function which develops very suddenly and is usually reversible.

Functions of the Kidney

If you keep in mind these key functions of the kidney, understanding AKI is quite simple.

• Volume regulation: The kidneys regulate how much volume we have. If there is excess fluid to excrete, it is removed through urine. Alternatively, if there is a need to retain fluid, this is again done through the kidney.
   
• Removal of waste products: Urea, for example, is removed through the kidneys.
   
• Electrolyte balance: The kidneys regulate several electrolytes, particularly sodium and potassium.
   
• Acid-base balance

Classification

AKI can be classified based on the underlying cause. There are three main classifications:

• Pre-Renal: The problem is occurring before the kidneys
• Renal: A kidney problem
• Post-Renal: There’s a problem occurring after the kidney

Pre-Renal Causes

Pre-renal causes are those which decrease the blood flow to the kidney, which in turn reduces the glomerular filtration rate (GFR). Furthermore, this reduced perfusion can also result in injury to the cells, potentially causing acute tubular necrosis.

• Hypovolaemia
  • Haemorrhage
  • Burns
  • Pancreatitis
     
• Hypotension
  • Myocardial infarction resulting in decreased cardiac output meaning less perfusion to the kidney
  • Septic shock
     
• Selective hypoperfusion specifically to the kidneys
  • Renal artery stenosis
     
• Afferent and efferent control: Remember, to increase GFR, you can either vasodilate the afferent arteriole or vasoconstrict the efferent arteriole. However, anything that interferes with this can disrupt regulation of the lumen size for these vessels. For example:
   
  • Vasodilation of Afferent: NSAIDs can inhibit the vasodilatory response of renal prostaglandins which helps to dilate the afferent arteriole, resulting in ischaemia.
  • Vasoconstriction of Efferent: Both ACE inhibitors and ARBs block efferent arteriolar vasoconstriction
     
• Hepatorenal syndrome: This is a syndrome whereby AKI is seen in the context of advanced liver disease. The underlying mechanism is thought to be related to renal vasoconstriction:
  • Cirrhosis/portal hypertension: Causes release of vasodilators which results in systemic vasodilation
  • System vasodilation results in a drop of blood pressure activating compensatory systems including the renin-angiotensin-aldosterone system (RAAS).
  • This causes renal vasoconstriction. The cycle continues – more cirrhosis = further vasodilation = fall in systemic vascular resistance = activation of RAAS = renal hypoperfusion

Renal or Intrinsic Causes

This is where there is direct damage to the kidney tissue, meaning the kidney cannot carry out its usual functions. Causes include:

• Acute tubular necrosis (ATN): Descriptive term for when the renal tubular cells are damaged and die.
  • Happens either because of nephrotoxins or ischaemia
  • Ischaemic ATN: Can be preceded by a pre-renal issue e.g. hypovolaemia
  • Nephrotoxic ATN:
    • Exogenous toxin: Drugs such as aminoglycosides, radiological contrast or calcineurin inhibitors
    • Endogenous toxin: For example, myoglobin from rhabdomyolysis
       
• Acute interstitial nephritis: Inflammation of the renal interstitium although renal tubules can also be involved. There are three main causes:
  • Infections: This can be viral, bacterial, fungal etc
  • Drugs: NSAIDs, aminoglycosides cephalosporins, macrolides, penicillin, furosemide, allopurinol and more.
  • Autoimmune Conditions: For example, Sjögren’s syndrome
     
• Glomerulonephritis
   
• Intratubular obstruction e.g. multiple myeloma

Post-Renal Causes

Post-renal causes comprise of obstructions of the urinary tract, leading to high pressures that are transmitted to the nephrons. After time, this can result in a fall in GFR. Examples include:

• Renal stones
• Tumours
• Benign prostatic hypertrophy
• Urethral stricture

Risk Factors

• 65 and over
• Diabetes
• Hypertension
• CCF
• CKD
• Patients with renal transplant
• Sepsis
• Contrast agents
• Being on nephrotoxic drugs e.g.
• NSAIDs
• ACE inhibitors
• ARBs 

Clinical Features

AKI can be completely asymptomatic, which is why it’s important to consider the possibility of patients developing AKIs, particularly if they have risk factors or if they are in hospital. There are various different criteria to detect AKI. NICE recommends using the following criteria:

• Rise in serum creatinine of ≥26 micromol/L within 48 hours
   
• ≥50% rise in serum creatinine which is known or presumed to have been within a week
   
• Urine output falling to <0.5ml/kg/hour for more than 6 hours in adults, and 8 hours in children and young people
   
• ≥25% fall in eGFR in children and young people within the past week

Investigations

Bedside

• Observations: Is the patient hypotensive/hypovolaemic?
• History and examination
  • Is there pulmonary oedema?
  • Is there a palpable bladder?
• Fluid status: Are there signs of hypovolaemia? Are there signs of hypervolaemia?
  • Heart rate, blood pressure, capillary refill, quality of pulse (bounding, thready)
  • JVP
  • Skin turgor and mucous membranes
  • Peripheral oedema, pulmonary oedema, ascites
• Fluid balance/input-output charting: Monitor with a fluid chart
• Urine dipstick
  • Negative: Usually pre-renal cause
  • Blood and protein: Consider glomerular disease
  • Leucocytes: Consider allergic interstitial nephritis or infection
• Bladder scan: Quick and easy bedside test to assess the volume of the bladder. Useful to rule out urinary retention.
• ECG: Particularly if you are concerned about electrolyte abnormalities such as hyperkalaemia

Bloods

• Full blood count
• Urea and electrolytes: For monitoring electrolytes, especially hyperkalaemia, and renal function
• Liver function test: Looking for hepatorenal syndrome
• VBG: For assessment of pH
• Renal screen:
  • Immunoglobulins (IgG, IgA, IgM)
  • Serum electrophoresis: Multiple myeloma
  • Complement (C3 and C4): SLE
  • ANA: SLE, Sjogren’s, Scleroderma
  • ANCA: Granulomatosis with polyangiitis, Churg-Strauss, microscopic polyangiitis
  • Rheumatoid Factor

Imaging

• CXR: Looking for pulmonary oedema
• US Renal Tract: For assessment of obstruction
• Non-contrast CT Kidneys, Ureters, and Bladder (KUB): Giving contrast is usually contraindicated in AKI
• Magnetic resonance angiogram: To identify arterial disease

Management

Supportive

• Stop nephrotoxic drugs. Stop the DAMN drugs is a helpful mnemonic to remember which drugs are pertinent to stop:
  • Diuretics
  • ACE inhibitors/ARBs
  • Metformin
  • NSAIDs
• Monitor fluid balance: Fluid overload can occur if patients receive too much fluid despite not being able to excrete fluid, which can result in pulmonary oedema or dilutional hyponatraemia. Alternatively, if there is hypovolaemia, this may require fluids or blood depending on the cause
• Monitor electrolytes and treat any disturbances
• Renal replacement therapy: If people have any of the following which are not responding to medical treatment, they may require RRT.
  • Hyperkalaemia
  • Fluid overload
  • Pulmonary oedema
  • Metabolic acidosis
  • Uraemia: Consequences include pericarditis and encephalopathy
• Renal dosing: Ensure that the patient’s regular medications are at the correct doses given their renal function; for example, low-molecular weight heparins (renal prophylactic doses).

Definitive

Definitive management depends on treating the underlying cause. For example:

• Pre-renal: Rehydration with IV fluids
• Renal: Patient will likely require a biopsy and specialist treatment
• Post-renal: Relieving the obstruction (will require urological input). This may be done via a nephrostomy or a stent.

Complications

• Hyperkalaemia
• Metabolic acidosis: Protons can accumulate due to inability to excrete them through the kidney resulting in a metabolic acidosis
• Pulmonary oedema: Due to fluid overload
• Uraemia
• Fluid overload

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922664/

https://www.nice.org.uk/guidance/cg169/documents/acute-kidney-injury-nice-version2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034033/

https://www.karger.com/Article/Fulltext/351648

https://emedicine.medscape.com/article/238064-overview#a5

https://www.ncbi.nlm.nih.gov/books/NBK507815/

https://www.aafp.org/afp/2003/0615/p2527.html

https://www.ncbi.nlm.nih.gov/books/NBK482323/

https://cks.nice.org.uk/acute-kidney-injury#!scenario

https://www.ncbi.nlm.nih.gov/books/NBK430856/

https://cks.nice.org.uk/topics/acute-kidney-injury/management/management-of-acute-kidney-injury/