Rhabdomyolysis and myoglobinuria
Peer reviewed by Dr Hayley Willacy, FRCGP Last updated by Dr Colin Tidy, MRCGPLast updated 28 Apr 2025
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What is rhabdomyolysis?1
Rhabdomyolysis (lysis of skeletal muscle cells) is a clinical syndrome of acute or subacute localised or generalised myalgia and weakness, associated with a rapid rise in the serum creatine kinase (CK) level:
In isolation, the clinical symptoms combined with a CK cut-off value of above 1000 IU/L or CK more than 5 times upper limit of normal represents mild rhabdomyolysis.
Additional myoglobinuria and acute kidney injury indicate severe rhabdomyolysis.
This definition holds true after exclusion of elevated CK due to other aetiologies such as myocardial infarction, status epilepticus or chronic neuromuscular disease. The coexistence of rhabdomyolysis in these aetiologies is also a possibility with acute elevation of CK.
What is myoglobinuria?1
Myoglobin is normally bound to plasma globulins, and has a rapid renal clearance with a half-life of 2-3 hours. A small quantity of filtered myoglobin (0.01-5%) is normally excreted with urine. The normal concentration of myoglobin in the serum is below 5.7nmol/L (100 μg/L) and in urine below 0.57nmol/L (10 μg/L).
After the occurrence of muscle damage, the circulating myoglobin levels exceed the plasma protein binding capacity, reach the glomeruli and are eventually excreted in the urine. Before the urine becomes discoloured (dirty-brown) by myoglobin, the level of myoglobin in the urine must exceed 57000 nmol/L (100 mg/ dl).
In rhabdomyolysis, the level of myoglobin in the serum increases within 1–3 hours, reaches its peak in 8–12 hours, and then returns to normal within 24 hours after the onset of the injury. The detection of myoglobin in the blood or urine is pathognomonic for the diagnosis of rhabdomyolysis, provided that it is made in the initial phases of the syndrome (within the first 24 hours). Myoglobinuria is detected in 17% of the patients with rhabdomyolysis.
Pathophysiology of rhabdomyolysis
Myocyte function under normal circumstances is maintained by adenosine triphosphate-dependent channels which ensure effective cell ion levels and play a role in calcium efflux from myocytes.2 Damage to the myocyte membrane (for example, due to trauma or lack of energy for the cell membrane channels) causes an increase in the amount of calcium in the cell, which leads to apoptosis through various proteolytic enzymes.3 This leads to the muscle necrosis and the release of various substances into the circulation - for example, myoglobin, potassium, phosphate, creatine kinase (CK) and urate.4
The process is self-perpetuating in that damage to muscle cells releases further calcium which can then be taken up by the surrounding myocytes, causing further muscle necrosis and further leakage of ions and proteins into the circulation.5
Myoglobin is a skeletal muscle protein involved in metabolism, and myoglobinaemia usually occurs before a rise in creatine kinase (CK) in rhabdomyolysis. Any myoglobin that reaches the circulation will be filtered by the kidneys and can lead to acute kidney injury through either direct toxicity or precipitation, or both.6 This process is facilitated by an acidotic environment and hypovolaemia.6 Myoglobin can appear in the urine (myoglobinuria) causing 'tea-coloured' urine with a positive urine dipstick for blood. The latter can cause confusion with haematuria and haemoglobinuria.
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How common is rhabdomyolysis? (Epidemiology)7
About 25,000 cases of rhabdomyolysis are reported each year in the USA. The prevalence of acute kidney injury in rhabdomyolysis is about 5-30%. It can occur at any age but most cases are seen in adults. It is more common in men. African-American race, obesity, and age over 60, are factors that demonstrate a higher incidence of rhabdomyolysis. In children, infection is the most common cause.
High incidences occur during calamities such as earthquakes and war due to the occurrence of crush syndrome. .
Causes of rhabdomyolysis (aetiology)5 7
Any process which leads to muscle necrosis can lead to myoglobinuria and therefore an increased risk of rhabdomyolysis. For example:
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Alcohol misuse. Over-exertion. Trauma, burns and compartment syndromes (including major disasters (for example, earthquakes) where a significant amount of muscle injury is likely to occur). Drugs.8 For example: statins, erythromycin, corticosteroids, ecstasy,9 heroin, cocaine, atropine,10 ingestion of ethylene glycol and amphetamines (likely to cause muscle necrosis through a number of mechanisms such as, vasospasm). Neuroleptic malignant syndrome. Myositis and myocarditis. Infections, such as influenza virus, Epstein-Barr virus (EBV), streptococcus, legionella and malaria.11 Snake bites - for example, a bite from the sea snake.12 Acute tumour lysis - massive tumour lysis which occurs after starting chemotherapy.13 Hypothyroidism and hyperthyroidism . Meyer-Betz disease - muscle pain, weakness and myoglobinuria following strenuous exercise.14 Genetic disorders - for example, abnormalities of lipid metabolism (for example, carnitine deficiency) or abnormalities of carbohydrate metabolism (for example, phosphofructokinase deficiency). |
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Symptoms of rhabdomyolysis (presentation)7
Many features are nonspecific and therefore a high index of clinical suspicion is required - for example, elderly patients, history of trauma, history of a fall followed by long duration of lying on the floor.
There may be features relating to the underlying cause - for example, swollen and painful muscles, paraesthesia of limbs in compartment syndrome or muscle tenderness.
Nonspecific symptoms - for example, fever, malaise, anorexia, nausea and vomiting.
Elderly patients may present with confusion, agitation and delirium.
Patients may be anuric and clinically dehydrated.
Myalgia and muscle weakness.
'Tea-coloured' urine may be present.
Presenting features may also relate to the release of the intracellular electrolytes, which may be fatal:
Increased potassium ions - heart block, ventricular tachycardia, asystole.
Decreased calcium ions - may also be associated with arrhythmias and tetany.
Disseminated intravascular coagulation.
Diagnosis of rhabdomyolysis7
This is based on clinical grounds - for example, the supportive case history.
CK levels are persistently raised.
Urine - 'tea-coloured' and positive for blood on dipstick testing. Haemoglobinuria will look similar macroscopically and both will change the common urinalysis dipstick reagent even when there are no RBCs on the microscopy. They can be distinguished by using electrophoresis, spectrophotometry, or other techniques. There are also direct tests for myoglobinuria, such as immunoassays, but as the time course suggests myoglobinuria is present very early, their usefulness may be limited.
Electrolytes - high potassium, low calcium, high phosphate.
Bone scintigraphy, MRI, CT scan or ultrasound may be helpful in some cases.
Investigations to delineate the underlying cause may be indicated - for example, muscle biopsy and genetic testing in recurrent cases.
Complications of rhabdomyolysis7
The complications of rhabdomyolysis are the cause of mortality and morbidity in these patients. These include:
Hyperkalaemia causing arrhythmias and cardiac arrest.
Hypocalcaemia (worsened by hyperphosphataemia).
Hepatic abnormalities - but AST may be high representing muscle AST.
Acute kidney injury from precipitation and obstruction of renal tubules by myoglobinuria and hypovolaemia.
Pooling of fluid in the damaged muscle which adds to hypovolaemia and can lead to a compartment syndrome.
There may also be complications resulting from the original insult - for example, burns associated with sepsis. The presence of hyperkalaemia, metabolic acidosis and acute kidney injury are most likely to be associated with higher morbidity and mortality.
Treatment for rhabdomyolysis7
Fluid rehydration - needs to be prompt; this is the most important aspect of treatment, as it will lead to less precipitation and toxicity of myoglobin at the kidneys and dilute nephrotoxins.
Treat hyperkalaemia - calcium gluconate (if indicated) and dextrose-insulin infusions.
Diuretics - loop diuretics have been used but their use is controversial and the benefits appear to be marginal.
Alkaline diuresis - alkalinisation of the urine with bicarbonate can reduce the risk of acute kidney injury. Acetazolamide administration might prove useful, as it enhances urine alkalinisation.
If renal function fails to improve, patients are at risk of acute tubular necrosis, in which case haemodialysis may be necessary.
Hypocalcaemia and hyperphosphataemia need not be corrected unless dangerously low - they improve as CK falls.
Treat the underlying cause if needed.
Statins and myotoxicity15
Statins are widely used and their use has been associated with a reduction in mortality and morbidity in coronary heart disease and cerebrovascular disease.
They are associated with muscle aches and pains and can cause myositis and rhabdomyolysis which can be fatal.
Cerivastatin was the most frequently used statin with associated rhabdomyolysis and was subsequently withdrawn.
The risk of rhabdomyolysis with statins is increased in the elderly, with use of interacting medications (for example, fibrates) and hypothyroidism.
If patients on statins develop myositis (muscle pain, muscle tenderness and weakness) or myalgia then the statin should be stopped and CK checked urgently. If CK level is normal, consider changing to another member or restart at a lower dose with cautious monitoring. Presence of rhabdomyolysis will require termination of treatment, and management as described above.
Further reading and references
- Aleckovic-Halilovic M, Pjanic M, Mesic E, et al; From quail to earthquakes and human conflict: a historical perspective of rhabdomyolysis. Clin Kidney J. 2020 May 22;14(4):1088-1096. doi: 10.1093/ckj/sfaa075. eCollection 2021 Apr.
- Anwar H, Al Lawati A; Adolescent COVID-19-Associated Fatal Rhabdomyolysis. J Prim Care Community Health. 2020 Jan-Dec;11:2150132720985641. doi: 10.1177/2150132720985641.
- Gupta A, Thorson P, Penmatsa KR, et al; Rhabdomyolysis: Revisited. Ulster Med J. 2021 May;90(2):61-69. Epub 2021 Jul 8.
- Braithwaite JP, Al Khalili Y; Physiology, Muscle Myocyte. StatPearls, January 2025.
- Del Re DP, Matsuda T, Zhai P, et al; Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL. Mol Cell. 2014 May 22;54(4):639-50. doi: 10.1016/j.molcel.2014.04.007. Epub 2014 May 8.
- Beetham R; Biochemical investigation of suspected rhabdomyolysis. Ann Clin Biochem. 2000 Sep;37 ( Pt 5):581-7.
- Keltz E, Khan FY, Mann G; Rhabdomyolysis. The role of diagnostic and prognostic factors. Muscles Ligaments Tendons J. 2014 Feb 24;3(4):303-12. eCollection 2013 Oct.
- Torres PA, Helmstetter JA, Kaye AM, et al; Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Ochsner J. 2015 Spring;15(1):58-69.
- Stanley M, Chippa V, Aeddula NR, et al; Rhabdomyolysis. StatPearls, January 2025.
- Valiyil R, Christopher-Stine L; Drug-related myopathies of which the clinician should be aware. Curr Rheumatol Rep. 2010 Jun;12(3):213-20.
- Liechti ME, Kunz I, Kupferschmidt H; Acute medical problems due to Ecstasy use. Case-series of emergency department visits. Swiss Med Wkly. 2005 Oct 29;135(43-44):652-7.
- Akhtar S, Rai MK, Dutta TK, et al; Atropine-induced rhabdomyolysis: an uncommon and potentially fatal adverse drug J Postgrad Med. 2010 Jan-Mar;56(1):42-3.
- Mishra SK, Pati SS, Mahanta KC, et al; Rhabdomyolysis in falciparum malaria--a series of twelve cases (five children and seven adults. Trop Doct. 2010 Apr;40(2):87-8.
- Kularatne SA, Hettiarachchi R, Dalpathadu J, et al; Enhydrina schistosa (Elapidae: Hydrophiinae) the most dangerous sea snake in Sri Lanka: three case studies of severe envenoming. Toxicon. 2014 Jan;77:78-86. doi: 10.1016/j.toxicon.2013.10.031. Epub 2013 Nov 12.
- Adeyinka A, Bashir K; Tumor Lysis Syndrome. StatPearls, January 2025.
- Kasap B, Soylu A, Turkmen M, et al; An adolescent girl with Meyer-Betz syndrome. Clin Rheumatol. 2006 Nov;25(6):904-6. doi: 10.1007/s10067-005-0091-3. Epub 2005 Nov 19.
- Camerino GM, Tarantino N, Canfora I, et al; Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence. Int J Mol Sci. 2021 Feb 19;22(4). pii: ijms22042070. doi: 10.3390/ijms22042070.
Article history
The information on this page is written and peer reviewed by qualified clinicians.
Next review due: 27 Apr 2028
28 Apr 2025 | Latest version

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