Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study

Lilleng, Hallvard; Johnsen, Stein Harald; Wilsgaard, Tom; Bekkelund, Svein Ivar

doi:10.1515/cclm.2011.776

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…Nevertheless, compared with the Duch results, the upper limits of the reference intervals calculated in Vall d’Hebron laboratory were lower for all age groups for both CK and uric acid ( Fig 3 ). For CK, differences between currently used and calculated reference intervals are particularly extreme, which has been already observed in other studies [ 34 , 35 ]. This finding might be explained by the high incidence of some related comorbidities such as metabolic syndrome or high blood pressure [ 36 ] together with the use of statins.…”

Section: Discussionmentioning

confidence: 66%

Indirect determination of biochemistry reference intervals using outpatient data

et al. 2022

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The aim of this study was to determine reference intervals in an outpatient population from Vall d’Hebron laboratory using an indirect approach previously described in a Dutch population (NUMBER project). We used anonymized test results from individuals visiting general practitioners and analysed during 2018. Analytical quality was assured by EQA performance, daily average monitoring and by assessing longitudinal accuracy between 2018 and 2020 (using trueness verifiers from Dutch EQA). Per test, outliers by biochemically related tests were excluded, data were transformed to a normal distribution (if necessary) and means and standard deviations were calculated, stratified by age and sex. In addition, the reference limit estimator method was also used to calculate reference intervals using the same dataset. Finally, for standardized tests reference intervals obtained were compared with the published NUMBER results. Reference intervals were calculated using data from 509,408 clinical requests. For biochemical tests following a normal distribution, similar reference intervals were found between Vall d’Hebron and the Dutch study. For creatinine and urea, reference intervals increased with age in both populations. The upper limits of Gamma-glutamyl transferase were markedly higher in the Dutch study compared to Vall d’Hebron results. Creatine kinase and uric acid reference intervals were higher in both populations compared to conventional reference intervals. Medical test results following a normal distribution showed comparable and consistent reference intervals between studies. Therefore a simple indirect method is a feasible and cost-efficient approach for calculating reference intervals. Yet, for generating standardized calculated reference intervals that are traceable to higher order materials and methods, efforts should also focus on test standardization and bias assessment using commutable trueness verifiers.

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Section: Discussionmentioning

confidence: 66%

Indirect determination of biochemistry reference intervals using outpatient data

et al. 2022

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“…The majority of data used in the NORIP originated from Finland and Sweden, while only 13% derived from Denmark. Since the introduction of the NORIP only few studies from the Nordic countries have attempted to undertake the recommended validation of NORIP RIs in use for the general adult population [8][9][10]. This study provides data from the Lolland-Falster Health Study (LOFUS), a population-based survey undertaken in 2016-2020 in Lolland-Falster, a ruralprovincial region in Denmark with approximately 1,03,000 inhabitants [11].…”

Section: Introductionmentioning

confidence: 99%

Reference intervals for 12 clinical laboratory tests in a Danish population: The Lolland-Falster Health Study

Bruun-Rasmussen

Napolitano

Jepsen

et al. 2021

Scandinavian Journal of Clinical and Laboratory Investigation

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Reference intervals (RIs), developed as part of the Nordic Reference Interval Project 2000 (NORIP) are widely used in most European laboratories. We aimed to examine the validity of the NORIP RIs by establishing RIs for 12 frequently used laboratory tests based on data from a local Danish population and compare these local RIs with the NORIP RIs. Using an a posteriori direct sampling approach, blood sample data were assessed from 11,138 participants aged 18þ years in the Lolland-Falster Health Study (LOFUS), of whom 2154 turned out to meet criteria for being healthy for inclusion in establishing RIs according to the NORIP methodology. The 2.5th and 97.5th percentiles were calculated for alanine aminotransferase (ALAT), albumin, alkaline phosphatase, bilirubin, creatinine, hemoglobin, highdensity lipoprotein cholesterol, iron, low-density lipoprotein cholesterol, thrombocytes, total cholesterol, and triglycerides. When comparing our estimates with the NORIP, the lower reference limits (RLs) for bilirubin and iron were lower, and higher for ALAT, thrombocytes and triglycerides. Upper RLs were lower for albumin (males and females !70 years), bilirubin and iron, but higher for alkaline phosphatase, triglycerides and for creatinine in men. In LOFUS, approximately 20% of the participants were healthy and qualified for inclusion in the establishment of RIs. Several of the local RIs differed from the NORIP RIs.

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“…However, in 2012 a Norwegian study was published which included data of altogether 6904 persons. The 97.5 th percentiles of CK was 207 U/L (3.5 µkat/L) for women and 367 U/L (6.1 µkat/L) for men [31]. As this was a high-quality study with significantly more subjects, we advocate relying on these data as a guidance for individuals of European origin.…”

Section: What Is Still Normal? -The Reference Range Problemmentioning

confidence: 97%

Differential Diagnosis of HyperCKemia

Kley

Schmidt‐Wilcke

Vorgerd

2018

Neurology International Open

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Elevated serum creatine kinase (CK) activity is usually an indicator of muscle damage. HyperCKemia is often an incidental finding and should be controlled after refraining from physical activity for some days, especially in asymptomatic patients. Furthermore, data from recent studies indicate that the upper limits of normal (ULN) need to be revised upward. This review includes an algorithm for the differential diagnosis of CK elevation in patients without muscular symptoms. In the field of neurology, in particular myopathies and neuropathies with affection of the lower motor neuron can cause symptomatic hyperCKemia, with CK values >1000 U/l (16,7 µkat/l) being indicative of a primary muscle disorder. Diseases with very high CK values include subtypes of muscular dystrophies, idiopathic inflammatory myopathies and metabolic myopathies. However, a normal or only slightly elevated CK value does not exclude the presence of a myopathy. The individual diagnostic procedure (e. g., muscle imaging, special laboratory studies, muscle biopsy and genetic testing) depends on the clinical phenotype and the results of electrophysiological studies. HyperCKemia can also be an adverse effect of several drugs including statins. In asymptomatic patients, statin-associated CK elevations <5 times the ULN can be tolerated. In patients with higher CK values and/or muscle symptoms, LDL-cholesterol lowering therapy should be changed. Rhabdomyolysis is a potentially life-threatening condition and is accompanied by highly elevated CK values. Acute phase treatment includes preserving renal function and restoring metabolic derangements.

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Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study

Abstract: URL CK values in women and in men <50 years of age were in accordance with URL CK values given by the NORIP. In men ≥50 years, a higher URL was found and the findings suggest an upward adjustment of URL in this age group.

Cited by 4 publications

References 21 publications

Indirect determination of biochemistry reference intervals using outpatient data

Indirect determination of biochemistry reference intervals using outpatient data

Reference intervals for 12 clinical laboratory tests in a Danish population: The Lolland-Falster Health Study

Differential Diagnosis of HyperCKemia

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