Intended for healthcare professionals

Practice Rational Testing

Investigating raised creatine kinase

BMJ 2021; 373 doi: https://doi.org/10.1136/bmj.n1486 (Published 23 June 2021) Cite this as: BMJ 2021;373:n1486
  1. Eun Ji Kim, specialist registrar,
  2. Anthony S Wierzbicki, consultant
  1. Department of Metabolic Medicine/Chemical Pathology, Guy’s & St Thomas’ Hospitals, London, UK
  1. Correspondence to AS Wierzbicki Anthony.wierzbicki{at}kcl.ac.uk
  • What you need to know

  • Most elevations in creatine kinase are physiological or secondary to exercise and do not require further investigation unless likely to be secondary to newly prescribed drug therapies

  • Persistent symptomatic changes in creatine kinase warrant investigation for underlying secondary causes including endocrine, autoimmune, and genetic disorders

  • Measure creatine kinase if a patient on statin therapy develops muscle pain

A 76 year old man with hypercholesterolaemia is referred to the lipid clinic because of persistently raised creatine kinase activity of 1000 IU/L or above (reference range 40-320 IU/L) after trying multiple statins. He describes no significant myalgia but had some proximal muscle weakness, which is demonstrated when he stands up from a seated position and when walking upstairs.

Creatine kinase (known previously as creatine phosphokinase or CPK) is distinct from creatinine and is a biomarker of muscle damage. The reference range for normal creatine kinase is 40‐320 IU/L for men and 25‐200 IU/L for women, though this may vary across laboratories and assays. Creatine kinase levels are dependent on age, sex, and muscle mass: the upper limit of normal (ULN) for men is higher than in women, and ageing is associated with reduced muscle mass, so minor increases in creatine kinase may indicate a greater extent of muscle damage in older adults.1 Pathologies involving muscle include myalgia (muscle pain with no creatine kinase rise), myopathy (muscle pain with creatine kinase rise), and rhabdomyolysis (muscle pain, weakness, and/or swelling with myoglobinuria and elevated creatine kinase). Creatine kinase can also be elevated without any muscle symptoms.2 Moreover, no clear correlation exists between creatine kinase activity and the extent of actual muscle injury. That said, creatine kinase >5000 IU/L (10-50 times the upper limit of normal) should prompt consideration of rhabdomyolysis.

What can cause an elevated creatine kinase?

Most cases of raised creatine kinase can …

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