QuestionSBA
QuestionChoice
Pre-renal uraemia is a very common cause of acute kidney injury in hospitals. The creatinine and urea can rise to these levels if the kidneys are very poorly perfused, either from shock or severe dehydration, although the kidneys would hold on to electrolytes with very concentrated urine. Urinary sodium would be <10mmol/L in this case, and so makes this a less likely cause for this patient's symptoms
33071
d
Pre-renal uraemia triggered by sepsis
QuestionChoice
Post-infectious glomerulonephritis can occur after almost any infection, but typically occurs 1-4 weeks following infection. Classically it presents following pharyngeal infection with Streptococcus pyogenes. While it can present with acute kidney injury and frank haematuria/dark brown urine, it would usually also present with generalised oedema and hypertension due to salt retention
33072
e
Post-infectious glomerulonephritis
QuestionChoice
This patient has had an infection followed by 5 days of intravenous gentamicin - a nephrotoxic medication. Worsening renal function with dark brown urine should raise suspicion of acute tubular necrosis. This is confirmed with a raised urinary sodium, implying less tubular modification of the glomerular filtrate with increased urinary electrolyte losses
33068
a
Acute tubular necrosis
QuestionChoice
Renal vein thrombosis can rarely occur following deep vein thrombosis in the legs - a common complication following knee surgery. It would unlikely present in an otherwise well adult unless there were severe dehydration or increased hypercoagulable state. If it were to cause such a severe acute kidney injury, it would present with haematuria and flank pain - opposed to dark brown urine with raised urinary sodium
33070
c
Renal vein thrombosis
QuestionChoice
Acute interstitial nephritis (AIN) is most commonly caused by medications (70-75% of cases), predominantly beta-lactam antibiotics, NSAIDs, rifampicin, ciprofloxacin, and diuretics. Classically patients with drug-induced AIN present with rash, pyrexia, and eosinophilia. They would also unlikely present with dark brown urine and more often present with urinary sediment of white cells, red cells, and white cell casts. Gross haematuria would also be distinctly unusual in AIN
33069
b
Acute interstitial nephritis
Concept
Chapter
# Summary

Acute Tubular Necrosis (ATN) is the most prevalent cause of intrinsic acute kidney injury (AKI), characterised by parenchymal damage that may be caused by an ischaemic, nephrotoxic or inflammatory insult. Signs and symptoms are not specific to ATN as a cause of AKI, and include oliguria, fatigue and nausea. Evidence of an underlying cause should be sought, for example hypovolaemia (e.g. severe diarrhoea and vomiting, burns), exposure to nephrotoxic drugs, rhabdomyolysis or sepsis. Investigations include urinalysis, urinary sodium, urinary osmolality and U&Es. Management is supportive and involves correcting the underlying cause, 
optimising volume status with IV fluids and considering dialysis in severe cases.

# Definition

Acute Tubular Necrosis (ATN) is a common cause of acute kidney injury (AKI), where renal tubular epithelial cells are damaged either due to a nephrotoxic agent or ischaemic insult. Despite the name, necrosis is not seen in the majority of cases - as such, ATN is sometimes referred to as "acute tubular injury".

In ischaemic ATN, injury to renal tubular endothelial cells is followed by epithelial cell injury, whereas nephrotoxic agents directly damage epithelial cells. Tubular cells apoptose and slough off to form casts that obstruct the tubular lumen, causing renal impairment and oliguria.

# Epidemiology

- ATN is the leading cause of intrinsic AKI
- It is often seen in acutely unwell inpatients and is a poor prognostic factor
- It is responsible for the majority of cases of AKI in patients admitted to intensive care
- The majority of cases are due to ischaemia
- Risk factors include:
- Hypovolaemia
- Older age
- Chronic kidney disease
- Recent use of nephrotoxic drugs

# Aetiology 

**Ischaemic causes** - usually due to prolonged hypotension

- Hypovolaemia
- Diarrhoea and/or vomiting
- Haemorrhage
- Dehydration
- Burns
- Renal losses (diuretics, osmotic diuresis)
- Third-spacing (e.g. severe pancreatitis)
- Systemic vasodilation
- Anaphylaxis
- Septic shock (also has toxic effects on the kidneys)
- Surgery, due to a combination of:
- Fluid losses
- Haemodynamic changes under anaesthesia
- Interruption of renal perfusion e.g. supra-aortic clamping in abdominal aortic aneurysm surgery

**Nephrotoxic causes**

- Medications, for example:
- Aminoglycoside antibiotics (e.g. gentamicin)
- Antifungals (e.g. amphotericin)
- Chemotherapy agents (e.g. cisplatin)
- Antivirals (e.g. tenofovir)
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Contrast agents
- Myoglobin (rhabdomyolysis)
- Haemoglobin (intravascular haemolysis, e.g. transfusion reactions, autoimmune haemolytic anaemia)

# Signs and Symptoms

There may be signs and symptoms of the cause of ATN (e.g. dehydration, nausea and vomiting)

Non-specific presenting features of AKI may be present, including:

- Lethargy and malaise
- Nausea and vomiting
- Oliguria or anuria (polyuria may be seen in the recovery phase)
- Confusion
- Drowsiness
- Peripheral oedema

# Differential Diagnosis

- **Pre-renal AKI** occurs when reduced renal perfusion and/or hypotension cause renal impairment; patients are often dehydrated but improve rapidly with treatment (unlike in ATN)
- **Acute interstitial nephritis** often occurs as a hypersensitivity reaction to a medication (but may also be triggered by autoimmune disease or infections); the classic triad is of a rash, fever and eosinophilia
- **Post-renal AKI** occurs due to urinary tract obstruction, for example renal stones, prostatic enlargement or a blocked catheter; symptoms of obstruction such as pain are often present and there may be hydronephrosis on imaging

# Investigations

**Bedside:**

- **Urine microscopy** shows muddy brown granular casts and renal tubular epithelial cells 
- **Urinary sodium** is key to differentiating pre-renal AKI from ATN - sodium is low in pre-renal AKI and high in ATN (usually > 40 mmol/L)
- **Urine osmolality** is low as urine concentrating capacity is impaired (< 450 mOsmol/kg)
- **Urine dip** may be falsely positive for blood if there is myoglobinuria or haemoglobinuria
- **Blood gas** to assess for acidosis and hyperkalaemia that may complicate AKI
- **ECG** looking for hyperkalaemic changes

**Bloods:**

- **U&Es** to confirm renal impairment and assess electrolytes
- **Urea:creatinine ratio** is low in ATN as water, sodium and urea are not retained unlike in pre-renal AKI
- **Full blood count** may show anaemia in some causes of ATN (e.g. haemorrhage, haemolysis); there may be a leukocytosis in sepsis
- **Creatine kinase** if rhabdomyolysis is suspected
- **Liver function tests** may show a concurrent ischaemic liver injury 
- **Bone profile** may be abnormal e.g. hypercalcaemia causing dehydration
- **CRP** may be raised in some causes of ATN e.g. sepsis
- **Blood cultures** should be sent in suspected sepsis
- **Coagulation screen** may show a prolonged aPTT due to platelet dysfunction secondary to uraemia

**Imaging:**

- **Ultrasound KUB (kidneys, ureters and bladder)** to rule out obstructive causes and assess renal size and structure - usually normal in ATN

**Special tests:**

- **Renal biopsy** is not required unless there is suspicion of a primary renal disease - in ATN histology shows loss of tubular epithelial cells with exposed areas of basement membrane

# Management

**Conservative:**

- Identify and treat the underlying cause (e.g. haemorrhage)
- Avoid giving further nephrotoxic medications (e.g. NSAIDs, ACE-inhibitors)
- Fluid balance monitoring and consider catheterisation

**Medical:**

- IV fluids to correct hypovolaemia and/or hypotension
- Blood products are preferred in haemorrhage
- Medical management may be required for the underlying cause (e.g. antibiotics in sepsis)
- Vasopressors may be used with fluids in patients with shock

**Interventional:**

- Consider dialysis in AKI with complications (e.g. refractory fluid overload or uraemia)

# Prognosis

- ATN is a poor prognostic factor, with a mortality of approximately 50%
- Patients who are septic or require dialysis have mortality rates of up to 80%
- Survivors tend to have favourable outcomes, with around 5% going on to require renal replacement therapy 
- Complications are those of any AKI (see Acute Kidney Injury chapter for details)

# NICE Guidelines

[NICE CKS - Acute Kidney Injury](https://cks.nice.org.uk/topics/acute-kidney-injury/)

# References 

[StatPearls - Acute Renal Tubular Necrosis](https://www.ncbi.nlm.nih.gov/books/NBK507815/)

[Pathology Outlines - Acute tubular necrosis](https://www.pathologyoutlines.com/topic/kidneyatn.html)

[International Journal of Nephrology - Long-Term Outcome of Patients Followed by Nephrologists after an Acute Tubular Necrosis Episode](https://onlinelibrary.wiley.com/doi/10.1155/2012/361528)
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Acute Tubular Necrosis
Topic
33
Nephrology
6614
Acute tubular necrosis can occur following the use of nephrotoxic medications such as certain antibiotics, contrast agents, or chemotherapy drugs, leading to impaired kidney function, elevated creatinine levels, and dark brown urine due to the presence of damaged tubular cells and myoglobin.
A 71-year-old man has been admitted for an elective right total knee replacement. He suffers from a post-operative urinary tract infection and is given 5 days of gentamicin.


Following this, his condition deteriorates with worsening acute kidney injury and dark brown urine. His blood tests show:

||||
|---------------------------|:-------:|--------------------|
|Urea|14.1 mmol/L|2.5 - 7.8|
|Creatinine|678 µmol/L|60 - 120|
|Urinary Sodium (24hr)|350 mmol/24hrs|75 - 300|


Which of the following is the most likely cause of this patient's acute kidney injury?
a