CKing Precision in the Interpretation of Diagnostic Biomarkers.

Creatine kinase (CK) is a dimeric globular protein that includes 2 subunits.1 The different combinations of the 2 subunits of the CK dimer, CK-M and CK-B, lead to 3 isoforms of the cytoplasmic enzyme.2 CK-MM is primarily expressed in skeletal muscles and represents the greater part of serum CK. Two isoenzymes also exist in mitochondria.1 From a physiological perspective, CK is vital to catalyze the reversible exchange of high-energy phosphate bonds, which is crucial for energy buffering in tissues with variable energy demand, such as skeletal muscles.1 From a clinical perspective, the measurement of CK, a biomarker of muscle damage,3 is a routine part of the assessment of patients with several conditions. See Article by Siddiqui et al A frequent use of CK as a biomarker is in the assessment of patients with muscle pain or weakness while being treated with a statin, which is now broadly referred to as statin-associated muscle symptoms (SAMS).4,5 Because muscle aches and pains are unspecific, subjective, and frequently observed with multiple common conditions, CK measurement is a key component in the evaluation of patients reporting SAMS to identify those at risk of more severe muscle problems, such as myopathy or rhabdomyolysis (severe myopathy in the presence of myoglobinemia or myoglobinuria and renal impairment/failure).5 Fortunately, severe SAMS accompanied with CK elevation >10× the upper reference limit (URL) are extremely rare, occurring in 1 per 1000 to 1 per 10 000 patients per year.5 For the clinician, muscle symptoms in the presence of no or only minor to modest CK elevations represent a particular challenge to discriminate SAMS from other secondary causes (hypothyroidism, other drugs). In the case the former is suspected, this often leads to a laborious exercise, for both the patient and the clinician, that …