Comparative Neuromuscular Laboratory

Why the serum creatine kinase (CK) activity should not be ignored!

Contributed by Dr. G. Diane Shelton
Comparative Neuromuscular Laboratory,  University of California, San Diego

Measurement of serum creatine kinase (CK) activity is essential in the evaluation of suspected neuromuscular disease. In skeletal muscle CK plays a major role in energy generation, buffering cellular ATP and ADP concentrations by catalyzing the reversible exchange of high-energy phosphate bonds between phosphocreatine and ADP, regenerating ATP from ADP produced during muscle contraction (See figure below).The reaction catalyzed by CK allows energy storage as phosphocreatine when demand is low, and when energy demand increases; CK enables rapid restoration of the intracellular pool of ATP necessary for muscle contraction.Creatine kinase may also be involved with ADP-ATP translocase in an "energy shuttle" shifting ATP from the mitochondrial matrix to the cytoplasm. At least five isoforms of CK exist. MM-CK is a cytosolic form found in several domains of the myofiber where ATP consumption is high.MB-CK is found mainly in heart muscle.

Creatine kinase is a specific enzyme marker of myofiber damage and the one most commonly used in the diagnosis of muscle diseases. Other enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) may be elevated with myofiber damage but lack the tissue specificity of CK. Elevations of AST and ALT activity need to be assessed in combination with other tests and clinical information to rule out diseases of other organ systems.  A diagnosis of liver disease should not be made with elevations of AST and ALT alone in the absence of concurrent measurement of serum CK activity. If serum CK activity is not measured, misdiagnosis of a liver disease may be made when the actual problem is a myopathy. The analysis of CK isoenzymes may aid in the determination of muscle and cardiac specificity, but is not available in most diagnostic laboratories.  Cardiac troponin I has largely replaced CK isoenzyme testing in humans and may be of value for assessing myocardial damage in our animal species.

Serum CK activity can be persistently elevated in many diverse muscle diseases and does not necessarily equate to a diagnosis of myositis. Most notably CK is moderately to markedly elevated in necrotizing, inflammatory and dystrophic myopathies and is usually normal or only mildly elevated in non-inflammatory muscle diseases. The magnitude and persistence of CK elevation is an indication of severity and activity of muscle lesions. Transient elevation of serum CK activity may follow external muscle damage from many causes. The half-life of CK is very short lasting only about 2 hours, so should rapidly decline within several hours to a few days in these circumstances. Intramuscular injections of drugs can cause a transient increase in serum CK but should return to baseline values in about 3 days. Prolonged recumbency can elevate serum CK activity as much as 12-fold. Serum CK activity may also be transiently elevated during and after surgery with the peak increase within 6-12 hours.Electromyography can result in mild and transient CK elevation. Anorexia in cats may be associated with moderate to marked elevations in serum CK activity and should not be used directly for a diagnosis of myopathy until feeding has resumed. If the serum CK activity is persistently increased and external causes can be eliminated, an underlying muscle disease should be considered.

Serum CK activity should be included on every neuromuscular minimum database, and most importantly, on pre-neuter blood screens in young dogs. This is particularly true for breeds predisposed to muscle disease such as Labrador and Golden retrievers(for an example of how this is useful click here). However, CK activity is not elevated in all muscle diseases, and muscle disease should not be ruled out based on a normal CK activity. Marked or persistent increases of CK in a young dog may be indicative of a congenital or inherited muscle disease even though the animal may be clinically asymptomatic at the time. The most marked increases in serum CK activity (>20,000 IU/L) are associated with necrotizing myopathies or muscular dystrophies. Generalized inflammatory myopathies usually show moderate increases in CK activity (2,000-20,000 IU/L),while the CK activity in focal inflammatory myopathies such as masticatory muscle myositis (MMM), endocrine myopathies,neuropathies and other congenital muscle diseases are normal or only mildly increased (0-2000 IU/L). For a full discussion and reference list on the laboratory diagnosis of muscle disease in dogs and cats the reader is referred to the following invited review: Shelton GD. Routine and specialized laboratory testing for the diagnosis of neuromuscular diseases in dogs and cats. Vet Clin Pathol 2010;39(3): 278-295.