In which patients do we see elevated creatinine kinase (CK) levels?

Elevated Creatine Kinase: Clinical Contexts and Patient Populations

Elevated creatine kinase (CK) levels occur across a broad spectrum of clinical conditions, most commonly in patients with muscle injury, myopathies, statin therapy, rhabdomyolysis, and certain genetic disorders.

Trauma and Rhabdomyolysis

Severe limb trauma and crush injuries are major causes of markedly elevated CK levels, with values above 5 times normal (approximately 1000 IU/L) indicating rhabdomyolysis. 1

• In crush syndrome patients, CK levels exceeding 75,000 IU/L are associated with over 80% incidence of acute kidney injury. 1
• Young males with severe injury are more likely to have peak CK levels >5000 U/L, with median time to peak CK occurring at 17 hours post-admission. 2
• Older patients paradoxically develop acute kidney injury at lower CK thresholds despite having lower peak CK levels (1,637 U/L vs 2,604 U/L in younger patients). 2
• Electrical burns and trauma patients frequently develop rhabdomyolysis, with 93.33% of those developing acute renal failure showing CK levels >1250 U/L at admission. 3
• CK levels in rhabdomyolysis can range from 10,000 to 200,000 U/L or higher, with documented cases reaching nearly 1 million U/L in multicausal scenarios. 4

Statin-Associated Muscle Symptoms

Patients on statin therapy represent a common population with elevated CK, though most elevations are mild and non-specific. 1

• Non-specific muscle aches occur in approximately 5% of statin users in clinical practice (versus 1-5% in randomized trials), typically without significant CK elevation. 1
• Severe myositis with CK levels >10 times upper limit of normal is rare but requires immediate statin cessation. 1
• Rhabdomyolysis from statins is exceedingly rare (<1 death per million prescriptions), occurring most frequently with drug interactions involving CYP3A4 inhibitors, fibrates (especially gemfibrozil), macrolide antibiotics, and cyclosporine. 1
• Predisposing factors include: advanced age, female sex, low body mass index, Asian ancestry, renal or liver disease, hypothyroidism, and high levels of physical activity. 1

Genetic Myopathies

Pompe disease patients consistently demonstrate elevated CK, with infantile-onset cases showing the highest elevations (up to 2000 IU/L). 1

• Approximately 95% of late-onset Pompe disease patients have elevated CK, though some adults may have normal levels. 1
• CK elevation serves as a sensitive but non-specific marker requiring confirmation with acid alpha-glucosidase enzyme testing. 1

Idiopathic inflammatory myopathies (dermatomyositis, polymyositis, inclusion body myositis) present with elevated CK alongside proximal muscle weakness. 1

• Immune-mediated necrotizing myopathy shows particularly high CK elevations (>10 times upper limit of normal), especially in statin-induced cases associated with anti-HMGCR antibodies. 1
• Sporadic inclusion body myositis typically shows only minimal CK elevation despite significant muscle weakness. 1

Malignant Hyperthermia Susceptibility

Patients with malignant hyperthermia susceptibility may present with persistently elevated CK (idiopathic hyperCKemia) or recurrent rhabdomyolysis triggered by exercise or anesthesia. 1

• Investigation for malignant hyperthermia susceptibility is warranted in patients with idiopathic hyperCKemia after full neurological evaluation excludes other causes. 1
• These patients require genetic testing of RYR1 and CACNA1S genes alongside in vitro contracture testing. 1

Athletic Populations

Athletes, particularly those engaged in eccentric exercise or high-intensity training, commonly show elevated CK levels. 1

• Black individuals demonstrate higher baseline CK levels than South Asian or white individuals, related to larger muscle mass and higher tissue CK activity. 1
• Impact trauma (body checks, collisions) can drastically increase CK without reflecting internal muscle stress. 1
• CK peaks between 24-120 hours post-exercise depending on modality, with highly individual kinetics based on ethnicity, body composition, and exercise intensity. 1

Important Clinical Caveats

CK-MB elevation can occur in skeletal muscle trauma without myocardial injury—8.6% of severe skeletal trauma patients show CK-MB >5.0 EU/L with normal electrocardiograms and LD isoenzymes. 5

• Myoglobin measurement may be more sensitive than CK for early identification of acute kidney injury risk, with earlier peak plasma concentrations. 1
• In acute kidney injury settings, creatinine production falls due to reduced hepatic creatine synthesis, while muscle injury increases creatinine release, complicating interpretation. 1
• For myocardial infarction diagnosis, troponin has replaced CK-MB as the primary marker, with CK-MB now reserved for detecting reinfarction or periprocedural MI. 1