Why is Creatine Phosphokinase (CPK) elevated in rhabdomyolysis?

From the Guidelines

CPK is elevated in rhabdomyolysis because it is released from damaged skeletal muscle cells into the bloodstream, as evidenced by studies showing that raising CPK levels above five times normal is a sign of rhabdomyolysis 1. Rhabdomyolysis is a condition characterized by the breakdown of skeletal muscle fibers, resulting in the leakage of muscle cell contents into circulation. CPK, also known as creatine kinase (CK), is primarily found in muscle tissues where it catalyzes the conversion of creatine to phosphocreatine, playing a crucial role in cellular energy storage and utilization. When muscle damage occurs due to trauma, excessive exercise, medications (such as statins), toxins, infections, or metabolic disorders, the integrity of muscle cell membranes is compromised, allowing intracellular contents including CPK to escape into the bloodstream. Some key points to consider in the management of rhabdomyolysis include:

• CPK levels can rise dramatically in rhabdomyolysis, often exceeding 5,000-10,000 U/L and sometimes reaching 100,000 U/L or higher (normal range is typically 20-200 U/L) 1.
• The magnitude of CPK elevation generally correlates with the extent of muscle damage and can help guide treatment decisions, including the aggressiveness of fluid resuscitation needed to prevent acute kidney injury from myoglobin toxicity, which is another muscle protein released during rhabdomyolysis.
• It is probably recommended to perform a repeated bio-assessment combining plasma myoglobin, plasma creatine phosphokinase (CPK) and kalaemia measurements to detect acute kidney injury in patients suffering from post-traumatic acute rhabdomyolysis after limb traumatic injury 1. The goal of treatment is to reduce morbidity and mortality associated with rhabdomyolysis, and CPK levels can serve as a useful marker for monitoring the effectiveness of treatment and guiding clinical decision-making 1.

From the Research

CPK Elevation in Rhabdomyolysis

• CPK (Creatine Phosphokinase) is an enzyme found in the heart, brain, and skeletal muscle, and its elevation is a key diagnostic marker for rhabdomyolysis, a condition characterized by the breakdown of skeletal muscle 2.
• In rhabdomyolysis, the breakdown of skeletal muscle leads to the release of CPK and other intracellular contents into the bloodstream, resulting in elevated CPK levels 2.
• A CPK level of at least 5 times the upper limit of normal is considered an important diagnostic marker for rhabdomyolysis 2.
• However, CPK alone may not be a sensitive marker for rhabdomyolysis-induced acute kidney injury (AKI) in some cases, as seen in a study where a patient presented with severe AKI and normal CPK levels 2.

Mechanism of CPK Elevation

• The breakdown of skeletal muscle in rhabdomyolysis leads to the release of CPK into the bloodstream, resulting in elevated CPK levels 3.
• The extent of CPK elevation can be correlated with the severity of muscle damage, with higher levels indicating more extensive muscle breakdown 4.
• Peak CPK levels are often reached within 3 days of muscle injury, and a peak CPK level of at least 5000 U/L has been shown to be 55% specific and 83% sensitive for the prediction of AKI requiring renal replacement therapy 4.

Clinical Implications

• Elevated CPK levels are a key diagnostic marker for rhabdomyolysis, and their measurement is essential for the diagnosis and management of this condition 5.
• However, the use of bicarbonate therapy, which has traditionally been used to treat patients with rhabdomyolysis, has been shown to have limited benefits in reducing AKI or improving mortality 5.
• Alternative biomarkers, such as aspartate aminotransferase (AST), have been proposed as potential markers for the diagnosis and monitoring of rhabdomyolysis in the absence of CPK testing 6.
• A threshold concentration of AST ≥110 U/L has been shown to have excellent sensitivity for detecting CPK concentration ≥5,000 U/L on day of admission in patients with rhabdomyolysis 6.