Acute Tubular Necrosis | AKI | Renal Tubular Necrosis

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Introduction

Acute tubular necrosis (ATN) is a form of intrinsic renal injury where damage occurs to the renal tubular epithelial cells.

ATN is the most common cause of acute kidney injury (AKI). The incidence of ATN is estimated at 88 cases per 100,000 adults and accounts for 76% of cases of AKI in intensive care.¹

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Aetiology

ATN can result in AKI, characterised by a sudden decrease in the glomerular filtration rate (GFR). Any form of pre-renal AKI that is not treated promptly may progress to ATN.

ATN can arise from ischaemic, septic, or nephrotoxic causes.²

Ischaemic

Ischaemia damages renal tubules by depriving them of oxygen and nutrients, leading to oxidative stress. Ischaemic causes of ATN can be split into local and systemic hypoperfusion.⁴

Local hypoperfusion

Causes of local hypoperfusion to the kidneys include:

Systemic hypoperfusion

Causes of intravascular volume depletion include:

• Diarrhoea
• Vomiting
• Poor oral intake
• Haemorrhage
• Burns
• Surgery
• Third spacing of fluid (e.g. ascites, bowel obstruction)

Other causes of systemic hypoperfusion include:

Sepsis

As well as causing systemic hypoperfusion and renal ischaemia, sepsis can also contribute to ATN through a systemic inflammatory response syndrome.²

Nephrotoxicity

Some medications or other toxins (including recreational drugs) can cause direct damage to tubular epithelial cells. This may be potentiated in the presence of other risk factors such as ischaemia or sepsis.⁵

Endogenous substances can also cause direct injury to tubular cells, such as myoglobin in rhabdomyolysis, or immunoglobulin components in myeloma.

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Clinical features

History

ATN presents very non-specifically with general symptoms of AKI, which can include:

• Oliguria or anuria
• Nausea and vomiting
• Confusion
• Lethargy
• Dyspnoea
• Peripheral oedema: due to fluid overload ²

Other important areas to cover in the history include:

• Reason for admission to hospital
• Past medical history (e.g. vascular disease, heart disease, diabetes mellitus, hypertension, underlying chronic kidney disease)
• Medication history (e.g. prescribed or over-the-counter medications, recreational drugs)
• Recent administration of iodinated radiological contrast media ²

Clinical examination

ATN does not lead to any specific clinical signs. As with history, examination should focus on the presence of risk factors for ATN or complications of AKI.²

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Differential diagnosis

Relevant differential diagnoses in suspected ATN include:

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Investigations

Suspected ATN (or other forms of AKI) should prompt testing of urea and electrolytes.

Further investigations should be considered to identify the cause of ATN or complications of AKI.

Bedside investigations

Relevant bedside investigations include:

• 12-lead ECG: may indicate features of hyperkalaemia
• Urine output: to identify oliguria or anuria
• Urinalysis: may show haematuria, proteinuria and high specific gravity

Laboratory investigations

Relevant laboratory investigations include:

• Full blood count: may show anaemia or thrombocytopenia
• Urea and electrolytes: typically elevated creatinine, urea, sodium, potassium and decreased bicarbonate 
• Bone profile: may show elevated phosphate and a low/normal calcium. Hypercalcaemia may be caused by myeloma or other malignancies.
• Blood gas: for evidence of metabolic acidosis
• Coagulation screen: identify hypercoagulability
• Creatine kinase: elevated in rhabdomyolysis 
• Urine toxicology screen: can identify drug/toxin exposure (e.g. cocaine, heroin).
• Urine microscopy: may show muddy brown casts (highly suggestive of ATN) or crystals that may be consistent with drug toxicity ^6-7

Imaging

Relevant imaging includes:

• Chest X-ray: if suspected pulmonary oedema
• Ultrasound kidneys, ureters and bladder (KUB): if post-renal obstructive cause is suspected ⁷

Special tests

• Renal biopsy: may be indicated where the diagnosis is unclear (particularly when there is suspicion of some other intrinsic renal cause of AKI, such as glomerulonephritis), or where recovery of suspected AKI has not occurred within an appropriate time frame.⁸

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Management

General management

Management of ATN involves treating the underlying cause, including:

• Fluid resuscitation: to increase intravascular volume
• Vasopressors: if fluid resuscitation is ineffective, to increase renal perfusion
• Treating heart or liver failure: optimising renal blood flow
• Treating sepsis: optimising renal blood flow and reducing nephrotoxic insult
• Discontinuing or minimising unnecessary medications: stopping or reducing nephrotoxic insult ¹

Renal replacement therapy

Renal replacement therapy (usually haemodialysis or haemofiltration) may be required with:

• Metabolic acidosis: pH <7.15 or worsening acidaemia 
• Electrolyte abnormalities: refractory to medical therapy (e.g. hyperkalaemia) 
• Presence of dialysable toxins (e.g. methanol, lithium, aspirin)
• Fluid overload: refractory to medical management
• Uraemia (e.g. encephalopathy and pericarditis)⁸

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Complications

Complications of ATN include: 

Prognosis

Uncomplicated ATN prognosis is favourable in healthy patients once the underlying insult is identified and managed.

Higher mortality is seen with male sex, increasing age, underlying comorbidities, malignancy, oliguria, sepsis, invasive ventilation, multi-organ failure, and advanced severity of illness.

5-year survival rate is approximately 55%, and around 5% of patients may require long-term RRT.⁹

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Reviewer

Dr Mahzuz Karim

Consultant in Renal Medicine

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Editor

Dr Jamie Scriven

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References

1. Gill N, Nally JV, Fatica RA. Renal failure secondary to acute tubular necrosis: epidemiology, diagnosis, and management. Chest. 2005. Available from: [LINK].
2. Hanif MO, Bali A, Ramphul K. Acute Renal Tubular Necrosis. StatPearls. 2023. Available from: [LINK].
3. Cenveo. Renal tubules. Licence: [CC BY 3.0 US]. Available from: [LINK].
4. Schrier RW, Shchekochikhin D, Ginès P. Renal failure in cirrhosis: prerenal azotemia, hepatorenal syndrome and acute tubular necrosis. Nephrology Dialysis Transplantation. 2012. Available from: [LINK].
5. Perazella MA, Wilson FP. Preventing acute kidney injury through nephrotoxin management. Nature Reviews Nephrology. 2016. Available from: [LINK].
6. Mohsenin V. Urine microscopy for analysis of urine sediments. Adapted by Geeky Medics. License: [CC BY 4.0]. Available from: [LINK].
7. Mohsenin, V. Practical approach to detection and management of acute kidney injury in critically ill patient. Journal of Intensive Care. 2017. Available from: [LINK].
8. Negi S, Koreeda D, Kobayashi S, et al. Renal replacement therapy for acute kidney injury. Renal Replacement Therapy. 2016. Available from: [LINK].
9. Brito GA, Balbi AL, Abrão JM, et al. Long-term outcome of patients followed by nephrologists after an acute tubular necrosis episode. International Journal of Nephrology. 2012. Available from: [LINK].

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