Tubular Necrosis

Question 1

What is acute tubular necrosis?

Answer 1

• Abrupt and sustained decline in GFR within minutes to days after ischaemic / nephrotoxic insult.
• It leads to an abrupt rise in urea and creatinine.

Question 2

What are the risk factors for acute tubular necrosis?

Answer 2

• Pre-existing CKD
• CVD
• ECF volume depletion
• Multiple renal insults

Question 3

What are the complications of acute tubular necrosis?

Answer 3

• Hyperkalaemia
• Metabolic acidosis
• Decreased Ca²⁺
• Increased PO₄^3-
• Hypoalbuminaemia

Question 4

Describe the pathophysiology of acute tubular necrosis.

Answer 4

• Tubular injury due to ischaemic or toxic insult.
• Initially, it results in focal loss of tubular epithelial cells.
• Later, tubules go through a recovery phase where there is regeneration of tubular cells.
• This leads to urine which has high fractional excretion of sodium and the excretion of pigmented-granular casts or muddy brown casts.
  
  • This is how ATN is distinguished from acute interstitial nephritis or glomerular nephritis.

Question 5

What are the 2 causes of acute tubular necrosis?

Answer 5

• Ischaemia
• Nephrotoxin

Question 6

What are the toxic causes of acute tubular necrosis?

Answer 6

• Exogenous
  
  • Antibiotics such as aminoglycosides, cephalosporins and amphotericin B.
  • Antivirals
  • Antineoplastics such as cisplastin and methotrexate.
  • Contrast medium
    
    • Leads to contrast-induced nephropathy.
    • Can also cause vasoconstriction – so it can cause a nephrotoxic injury and an ischaemic injury.
  • Heavy metals
  • Ethylene Glycol
• Endogenous
  
  • Bacterial endotoxins
  • Myoglobin
    
    • From Rhabdomyolysis – if a patient has severe injury where skeletal muscle is damaged, myoglobin can be liberated into the bloodstream and damage renal tubules
  • Haemoglobin

Question 7

What are the ischaemic causes of acute tubular necrosis?

Answer 7

• Hypotension
• Shock
• Decreased circulating blood volume (has the same effect as hypotension)
  
  • Haemorrhage
  • Fluid losses – skin losses or GI losses
• Decreased effective circulating blood volume
  
  • Heart failure
  • MI
  • Liver failure – patient has the fluid but it is not being delivered to the kidneys.
  • Anaphylaxis (can lead to decrease in systemic vascular resistance, in effect leading to decreased effective circulating volume to the kidneys).
  • Vessel occlusion – blocks delivery of blood to the kidney (renal artery stenosis can be a cause of this).

Question 8

Describe the treatment for acute tubular necrosis.

Answer 8

• Correct the underlying problem.
  
  • Identify the nephrotoxic agent and stop it.
  • If injury – correct the rhabdomyolysis.
  • If infection is causing circulation of bacterial endotoxins and this is causing injury the infection should be treated.
  • If the cause is ischaemic, try to improve BP and if fluid is depleted that should be corrected.
  • Once these things have been done, treatment is supportive.
  • If the ATN is severe or rapidly progressing, early dialysis should be considered.

Question 9

How can acute tubular necrosis be prevented?

Answer 9

• Identify high risk patients and avoid using nephrotoxins if possible.
• If imaging is absolutely necessary and the patient needs contrast, patient can be given N-Acetylcystein (600-1200mg PO bid day) – before and after radiographic contrast. Also give IV fluid.
• Before contrast procedure, avoid use of diuretics, ACE-inhibitors and cyclosporine.