Biological variation of 20 analytes measured in serum from clinically healthy domestic cats

Abstract

The applications of data on biological variation include assessment of the utility of population-based reference intervals, evaluation of the significance of change in serial results, and setting of analytical quality specifications. We investigated the biological variation of 19 biochemistry analytes and total T4, measured in serum from 7 clinically healthy domestic cats sampled once weekly for 5 weeks. Samples were frozen and analyzed in random order in the same analytical run. Results were analyzed for outliers, and the components of variance, subsequently generated by restricted maximum likelihood, were used to determine within-subject and between-subject variation (CV and CV, respectively), as well as analytical variation (CV) for each analyte. Indices of individuality, reference change values, and analytical performance goals were calculated. The smallest CV and CV were found for calcium, chloride, and sodium, whereas the largest values were calculated for bile acids. Nine analytes (albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, cholesterol, creatinine, phosphate [phosphorus], total protein, total T4) demonstrated high individuality, indicating limited utility of population-based reference intervals. Individuality was low, and population-based reference intervals were thereby considered appropriate for 5 analytes (bile acids, calcium, fructosamine, glucose, potassium). The intermediate individuality observed for 4 analytes (creatine kinase, iron, magnesium, urea) indicated that population-based reference intervals should be used with caution.

Biological variation of routine haematology and biochemistry measurands in the horse

“…Creatine kinase, an indicator of skeletal muscle damage [25], also demonstrated large variation within and between-subjects (CV I 30.53% and CV G 27.96%) in this study ( Table 2). These values are comparable to those reported for biological variation of CK in cats [3,4], and likely represent 3 4 5 6 7 8 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Horse 4 6 8 10…”

“…Traditionally laboratory results have been assessed using populationbased reference intervals. However, recent studies in other species have demonstrated that many routinely measured variables demonstrate high between-subject variation [3][4][5][6][7]11,12]. Because the population-based reference intervals for these measurands are wide, these studies have demonstrated the value of individualised (subject-based) reference intervals [3,13].…”

Comparison of 2 assays for measuring serum total thyroxine concentration in dogs and cats

“…Quality assurance goals for TT4 attempt to show that the CV from assay results is not due simply to biological variation. Differences derived from CVi have been reported previously as 2.9% to 8.6% for cats 30 and 4.25% to 12.75% for dogs. 31 This suggests that the CTT4 in cats is just below the low threshold of quality goals (which is not a relevant difference), the MTT4 is within the range of quality goals, and the ITT4 also is within the range of historically assessed quality goals based on CVi.…”

Analytical quality goals—a review

“…Less BV causes more stringent BV‐based quality goals, which means that such quality goals may not be achievable by available technology (ie, by the current “state‐of‐the‐art”). For example, BV of sodium and chloride had CV I = 1% in 2 feline studies and CV I = 0% in a third feline study, which means that “desirable” analytical imprecision (CV A ) for these measurands would be ≤0.5%. These stringent quality goals, even if not reached, should be seen as aspirational and should motivate continued improvements in technology.…”

“…In contrast, BV‐based quality goals for measurands having large BV (eg, enzyme activities) may be too permissive to be useful in the laboratory. For example, the BV of pancreatic lipase immunoreactivity in dogs has CV I of 194%; bile acids in cats has CV I of 130%, and total bilirubin in cats has CV I of 88%, which means that “desirable” CV A for these measurands would be ≤97%, 65%, and 44%, respectively. Lack of BV data for some species. Most canine and feline biochemistry measurands have appropriate data from at least two BV studies which, in many cases, have found similar values for CV I .…”