From the Guidelines
Yes, Creatine Phosphokinase (CPK) can be normal in cases of myoglobinuria, as evidenced by the complex pathophysiological background of muscle damage and biomarker clearance. Typically, myoglobinuria occurs when muscle damage releases myoglobin into the bloodstream, which is then filtered by the kidneys, and this muscle damage usually also releases CPK, causing elevated serum levels 1. However, in some situations, myoglobinuria may occur with normal CPK levels, particularly if blood sampling occurs after CPK has normalized but while myoglobin is still being cleared, as CPK has a different clearance rate than myoglobin 1.
The timing of testing is crucial, as CPK typically peaks 24-36 hours after muscle injury, while myoglobin appears earlier and clears faster 1. Other markers like urine myoglobin, serum creatinine, and clinical symptoms should be assessed alongside CPK for a complete diagnostic picture. It is also important to consider that the measurement of plasma myoglobin may be more sensitive and specific than CPKs in identifying the risk of acute kidney injury, which is correlated with increased mortality 1.
Some studies suggest that the lymphatic transport of CK from the interstitial fluid is responsible for the delay from the damaging exercise and its detectability in the blood, which can lead to difficulties in interpreting enzyme activity in blood 1. Additionally, the proportion of inactivation of CK can vary intra- or inter-individually, resulting in varying degrees of underestimation of the actual muscle damage.
Given the complexity of muscle damage and biomarker clearance, it is essential to consider multiple factors and markers when evaluating suspected muscle injury, rather than relying solely on CPK levels. The most recent and highest quality study 1 highlights the importance of considering the pathophysiological background and timing of testing when interpreting CPK levels and other biomarkers.
Key points to consider:
- CPK can be normal in cases of myoglobinuria due to differences in clearance rates and timing of testing
- Myoglobin appears earlier and clears faster than CPK
- Other markers like urine myoglobin, serum creatinine, and clinical symptoms should be assessed alongside CPK
- The measurement of plasma myoglobin may be more sensitive and specific than CPKs in identifying the risk of acute kidney injury
- Lymphatic transport and inactivation of CK can lead to difficulties in interpreting enzyme activity in blood.
From the Research
CPK and Myoglobinuria
- CPK (Creatine Phosphokinase) is an enzyme found in the body, and its levels can rise when there is muscle damage, such as in the case of rhabdomyolysis, which can lead to myoglobinuria [(2,3,4,5,6)].
- Myoglobinuria is a condition where myoglobin is present in the urine, often as a result of muscle breakdown [(2,3,4,5)].
Normal CPK with Myoglobinuria
- A study published in 2018 reported a case of rhabdomyolysis with severe acute kidney injury (AKI) and normal CPK levels at presentation 3.
- This suggests that CPK alone may not be a sensitive marker for rhabdomyolysis-induced AKI in some cases 3.
- Another study found that myoglobin levels above 15 mg/L were most significantly related to the development of AKI and the need for hemodialysis 4.
Relationship between CPK and Myoglobinuria
- Elevated serum CPK levels are associated with mortality and inotropic requirement in critically injured adults 6.
- A linear correlation was demonstrated between the level of serum myoglobin and the serum concentrations of urate, CPK, aspartate transaminase (AST), and lactic dehydrogenase (LDH) in marathon runners 5.
- Myoglobin itself and the increased concentration of urate may contribute to acute renal failure 5.