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The creatine kinase reference interval. An assessment of intra- and inter-individual variation
Insights
Serum creatine kinase (CK) levels are consistent within individuals, despite wide variations between people. This finding impacts the clinical usefulness of CK testing for conditions like Duchenne muscular dystrophy carriers.
Area of Science:
- Biochemistry
- Genetics
- Clinical Diagnostics
Background:
- Serum creatine kinase (CK) reference ranges exhibit significant inter-individual variability, exceeding one order of magnitude.
- This broad variability complicates the interpretation of CK levels, particularly for identifying female carriers of Duchenne muscular dystrophy.
- The clinical utility of serum CK testing is limited by overlapping normal and carrier ranges.
Purpose of the Study:
- To investigate whether the wide variation in serum CK levels is due to day-to-day fluctuations within individuals or inherent differences between individuals.
- To determine the consistency of serum CK activities within the same individual over time.
Main Methods:
- Tested serum CK levels in female medical students at weekly intervals and on multiple occasions.
- Standardized protocol included a 3-day exercise-free interval before each blood draw to minimize exercise-induced variations.
- Analyzed intra-individual (within-person) and inter-individual (between-person) variability using coefficient of variation (CV).
Main Results:
- Serum CK activities were found to be consistent within individuals, with a mean intra-individual CV of 19%.
- Inter-individual variability was significantly greater, with a CV of 47%.
- Even minor exercise within three days prior to venesection led to slightly elevated CK values, underscoring the need for standardized testing conditions.
Conclusions:
- Individuals exhibit consistent serum creatine kinase (CK) activities.
- The primary source of variation in serum CK levels is inter-individual differences, not day-to-day fluctuations.
- Standardized resting conditions are crucial for reliable CK testing, especially when assessing conditions with overlapping value ranges.
Abstract:
Serum creatine kinase (CK) values in reference populations generally vary by greater than one order of magnitude. This large range of variation overlaps the range of values found in female carriers of Duchenne muscular dystrophy and limits the clinical usefulness of serum CK testing. In order to examine whether the source of this variation is intrinsic variability of individual CK values, or whether the variation is due to day-to-day variation in each individual's CK activities, we tested 15 female medical students at weekly and 22 female medical students on at least 3 occasions. Each venesection followed a 3-day exercise free interval, according to a standard protocol, designed to minimise the effects of exercise. Each individual tended to have consistent CK activities. The range of variation in the same individuals on different occasions was small (the mean coefficient of variation, CV was 19%). There was a much greater range of serum CK activities between individuals (CV 47%). Even when sporting activities were excluded slightly higher values were found after minor exercise was recorded in the three days prior to venesection. The conclusion that individuals have consistent serum CK activities was supported by the results from a larger population tested under standardised resting conditions on three different occasions which yielded similar frequency distributions on each occasion.