QuestionSBA
QuestionChoice
Acute interstitial nephritis is a hypersensitivity reaction causing inflammation of the interstitium of the kidneys. This presents with a delayed presentation of fever, rash and acute kidney injury. It is typically a drug reaction with common causes including penicillin antibiotics, NSAIDs and proton pump inhibitors. The urine dipstick results typically found in acute interstitial nephritis include pyuria, but not haematuria. As this patient has presented with a dipstick positive for blood in the context of a long lie, rhabdomyolysis is the more likely diagnosis
33632
e
Acute interstitial nephritis
QuestionChoice
Dehydration can be a cause of pre-renal acute kidney injury, particularly in those who are elderly or have other risk factors such as dementia. In this case, this patient presents with myalgia, a urine dipstick positive for blood and changes to the colour of their urine. These are not features of dehydration and suggest a different cause. Therefore, rhabdomyolysis is the more likely differential
33629
b
Dehydration
QuestionChoice
Glomerulonephritis is a diverse group of conditions that can be separated broadly into nephrotic syndrome and nephritic syndrome. Nephrotic presents differently to this case, typically with a triad of oedema, hypercholesterolaemia and hypoalbuminaemia. It is diagnosed based on a high protein level in the urine. Nephritic syndrome causes blood in the urine; however, like the vast majority of glomerular disorders, it will also cause proteinuria. This is because glomerular damage causes a leak of protein and blood. As this patient did not have a urine dipstick positive for protein, glomerulonephritis is unlikely to be the cause of this presentation
33631
d
Glomerulonephritis
QuestionChoice
Rhabdomyolysis is a condition characterised by skeletal muscle breakdown. There are several typical features of rhabdomyolysis in this question. This is an elderly patient presenting after a long lie, which is a typical cause of rhabdomyolysis. The patient is complaining of soreness in their arms and legs, which may be myalgia associated with rhabdomyolysis (the breakdown of muscle tissue). Breakdown of skeletal muscle tissue releases myoglobin into the systemic circulation, which is associated with renal complications, including acute kidney injury. This explains the colour of this patient's urine, with urine in rhabdomyolysis typically described as being "cola coloured". The 3+ blood is actually a false positive reading for haemoglobin, as it is actually myoglobin responsible for this result
33628
a
Rhabdomyolysis
QuestionChoice
Stones can present with a dipstick positive for blood. However, they will also probably present with colicky abdominal pain, whereas this patient presents with generalised pain affecting their arms and legs. These features, in combination with a long lie, make a diagnosis of rhabdomyolysis more likely
33630
c
Renal calculi
Concept
Chapter
# Summary

Rhabdomyolysis refers to the breakdown of skeletal muscle, causing release of intracellular contents (including electrolytes and myoglobin) into the circulation and extracellular space. It often occurs after trauma or a long lie; other causes include excessive exertion, status epilepticus, compartment syndrome and medications such as statins. Presentation is classically with myalgia, weakness and brown urine (due to myoglobinuria). It is diagnosed by confirming that serum creatine kinase (CK) is 5 times the upper limit of normal. Myoglobin causes significant nephrotoxicity leading to acute kidney injury in many cases. Management is supportive, with aggressive IV fluids, correction of hyperkalaemia and treatment of any underlying cause.

# Definition

Rhabdomyolysis is a potentially life-threatening condition that occurs when there is rapid breakdown of skeletal muscle. Intracellular contents of muscle cells are released, including creatine kinase, myoglobin and potassium.

# Aetiology

There are a wide variety of causes of rhabdomyolysis, including:

- Prolonged immobilisation (e.g. a long lie in elderly patients who have fallen) 
- Crush injuries
- Severe burns
- High-voltage electrical injury
- Prolonged seizures
- Compartment syndrome
- Excessive physical exertion
- Medications (e.g. statins, fibrates, neuroleptic malignant syndrome)
- Recreational drugs (e.g. ecstasy, cocaine)
- Toxins (e.g. snake venom)
- Heatstroke 
- Myositis (e.g. viral or autoimmune) 
- Delirium tremens (alcohol withdrawal)
- Ischaemic injuries
- Metabolic or genetic disorders (e.g. glycogen storage diseases, muscular dystrophies)
- Diabetic ketoacidosis
- Thyroid storm

# Signs and Symptoms

Symptoms include:

- Muscle pain
- Weakness
- Tea-coloured urine
- Malaise
- Fevers
- Anorexia
- Nausea and vomiting

Signs on examination include:

- Tender and swollen muscles (often disproportionate to the injury sustained)
- Altered mental state - agitation, delirium
- Oliguria or anuria

# Differential Diagnosis

- **Compartment syndrome** may cause or complicate rhabdomyolysis or occur alone
- Often occurs after injury, or due to a deep vein thrombosis or tight cast or splint
- Presents with severe pain in the affected limb disproportion to the injury
- Other features of acute limb ischaemia may develop, e.g. paralysis, paraesthesia, pulselessness and pallor
- **Acute kidney injury (AKI)** may occur in the absence of rhabdomyolysis
- For example a patient admitted after a long lie may develop a pre-renal AKI due to dehydration but without rhabdomyolysis 
- Presenting features may include oliguria or anuria, malaise and confusion
- **Myositis** may be complicated by rhabdomyolysis but this is rare
- Typically patients present with a more chronic onset of symptoms of myalgia, diffuse weakness and fatigue
- Pain and muscular tenderness are variable
- There is a wide range of causes, including autoimmune, infective and malignancy-associated myositis
- **Deep vein thrombosis** presents with swelling, pain, tenderness and erythema of the affected limb (rather than widespread muscle involvement)

# Investigations

**Bedside tests:**

- **Urine dipstick** is falsely positive for blood due to myoglobinuria
- **Urine microscopy** shows no red cells in the urine
- **Venous blood gas** to rapidly obtain serum potassium; may show a metabolic acidosis
- **ECG** may show changes due to hyperkalaemia or hypocalcaemia

**Blood tests:**

- **Creatine kinase** is the key diagnostic test - a CK > 5x the upper limit of normal is expected
- **U&Es** looking for renal impairment and hyperkalaemia; creatinine is raised out of proportion to urea
- **Full blood count** as a baseline; white cells may be raised if inflammation or infection is driving rhabdomyolysis
- **Coagulation screen** to monitor for disseminated intravascular coagulation
- **Bone profile** may show hypocalcaemia initially as calcium deposits in necrotic muscle tissue; this may later be released causing hypercalcaemia; phosphate may be high
- **Liver function tests** may show a liver injury; AST and ALT will be raised due to muscle damage
- **Urate**, **lactate dehydrogenase** and **aldolase** are raised (these are non-specific)

**Imaging:**

- Imaging is not routinely required
- **MRI** is the imaging modality of choice, and will show oedematous muscles with features of myonecrosis in severe cases

**Special tests:**

- In cases of diagnostic uncertainty, further investigations may be required to look for an underlying cause
- Examples include **acetyl carnitine profile**, **urine organic acids**, **HIV serology** and an **autoimmune screen**
- **Muscle biopsy** may also be considered; this should be delayed for at least a month after an acute episode of rhabdomyolysis

# Management

**Conservative management:**

- Close input-output monitoring is required, especially for patients at increased risk of fluid overload (e.g. frail elderly patients)
- Catheterisation should be considered 
- Stop any medications that may be possible triggers (e.g. statins)
- Identify the underlying cause and initiate treatment (e.g. cooling measures for hyperthermia)
- Renal function and acid-base status should be closely monitored
- Early referral for intensive care and renal input is advised in severe rhabdomyolysis

**Medical management:**

- IV fluid rehydration - large volumes may be required to meet a target urine output of 200-300ml/hour (or 3 ml/kg/hour) until CK normalises
- Hyperkalaemia should be managed as per usual emergency guidelines, with calcium gluconate for myocardial protection and iV insulin/dextrose
- In some cases, IV sodium bicarbonate may be considered to correct acidosis (although this may exacerbate hypocalcaemia and so is not routinely used)
- Complications may require additional medical treatment e.g. correction of disseminated intravascular coagulation

**Interventional management:**

- Intensive care admission for renal replacement therapy may be required in severe rhabdomyolysis e.g. in cases of refractory hyperkalaemia or metabolic acidosis
- Some causes of rhabdomyolysis may require surgical intervention e.g. fasciotomies for compartment syndrome

# Complications

- **Acute kidney injury** is the major complication, which may lead to acute renal failure; it occurs due to a combination of hypovolaemia leading to renal ischaemia, tubular obstruction with heme pigment casts and direct tubular injury
- **Arrhythmias** including cardiac arrest may occur due to hyperkalaemia and hypocalcaemia
- **Metabolic acidosis** is common, often with an increased anion gap
- **Disseminated intravascular coagulation** is a rare complication that may occur due to release of prothrombotic substances from damaged muscle
- **Compartment syndrome** may occur secondary to inflammation and oedema of damaged muscles, especially after fluid resuscitation
- **Hypercalcaemia** occurs after initial hypocalcaemia due to release of calcium from injured muscle
- **Liver injury** is seen in up to 25% of patients - this is typically reversible 

# Prognosis

- Prognosis varies significantly depending on the severity of rhabdomyolysis
- Some patients may be asymptomatic, whereas in others the condition is life-threatening
- Up to 65% of patients with rhabdomyolysis develop acute kidney injury (AKI) as a result
- Mortality in severe rhabdomyolysis is 20% 
- Some residual muscle weakness in those who recover is common

# References

[Patient UK - Rhabdomyolysis and myoglobinuria](https://patient.info/doctor/rhabdomyolysis-and-other-causes-of-myoglobinuria)

[RCEM Learning - Acute Rhabdomyolysis](https://www.rcemlearning.co.uk/reference/acute-rhabdomyolysis/)

[Faculty of Intensive Care Medicine - Rhabdomyolysis](https://www.ficm.ac.uk/documents/case-of-the-month-27-rhabdomyolysis/)

[National Genomics Education Programme - Rhabdomyolysis](https://www.genomicseducation.hee.nhs.uk/genotes/in-the-clinic/presentation-adult-with-rhabdomyolysis/)

[Radiopaedia - Rhabdomyolysis](https://radiopaedia.org/articles/rhabdomyolysis)
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Rhabdomyolysis
Topic
33
Nephrology
6726
A 77-year-old female presents to the emergency department after their daughter found them on the floor in their home. The patient is unsure how long she was on the floor, but she said her arms and legs feel sore. A urine dipstick is performed, which shows 3+ blood. Her urine is also dark brown in colour.

What is the most likely diagnosis?
a