Comparison of serum and plasma SDMA measured with point-of-care and reference laboratory analysers: implications for interpretation of SDMA in cats

Abstract

Objectives: Symmetric dimethylarginine (SDMA) reflects the glomerular filtration rate (GFR) in people, dogs and cats. Initial assays used a liquid chromatography-mass spectroscopy (LC-MS) technique. A veterinary immunoassay has been developed for use in commercial laboratories and point-of-care (POC) laboratory equipment. This study sought to: determine POC and commercial laboratory (CL) SDMA assay imprecision; determine any bias of the POC assay compared with the CL assay; calculate observed total error of the POC assay and compare with analytical performance goals; and calculate dispersion and sigma metrics (σ) for POC and CL SDMA methods.

Methods: Two separate studies were performed that assessed: (1) imprecision, determined by evaluation of pooled feline plasma or serum; and (2) bias, assessed by comparing pooled plasma and serum results, as well as paired analyses of clinical samples from a single venepuncture measured using both analysers. Results were assessed in relation to performance goals. Dispersion and σ were calculated for both analysers.

Results: Bias between CL and POC analysers was consistent and high numbers of clinical results were outside performance goals across both studies. Imprecision was poor for both analysers for study 1 and improved to within quality goals for the CL analyser for study 2. Dispersion was at least 40%, meaning a measured result of 14 μg/dl represents a range of possible results from 8 μg/dl to 20 μg/dl.

Conclusions and relevance: Clinicians should be careful ascribing medical significance to small changes in SDMA concentration, as these may reflect analytical and biological variability. Analyser-specific reference intervals are likely required.

Keywords: Symmetric dimethylarginine; bias; dispersion; imprecision; method comparison; quality goal; sigma metrics; test interpretation.

Figure 1

Flow chart of study 1 procedures and statistics for pooled heparinised plasma samples to investigate symmetric dimethylarginine (SDMA) and creatinine imprecision and related calculations. CV_A = analyser coefficient of variation (imprecision); CV_I = individual coefficient of variation (biological variation) from prior study

Figure 2

Flow chart of study 1 procedures and statistical assessments to compare symmetric dimethylarginine (SDMA) results from a point-of-care (POC) analyser measured using heparinised plasma with SDMA results from a commercial laboratory (CL) analyser measured using serum. Samples were from healthy cats and cats with previously diagnosed kidney disease

Figure 3

Flow chart of study 2 procedures and statistics for pooled heparinised plasma samples and pooled serum samples to investigate symmetric dimethylarginine (SDMA) and creatinine imprecision and related calculations. CV_A = analyser coefficient of variation (imprecision); CV_I = individual coefficient of variation (biological variation) from prior study

Figure 4

Flow chart of study 2 procedures and statistical assessments to compare SDMA results from a point-of-care (POC) analyser and a commercial laboratory (CL) analyser measured using heparinised plasma from healthy cats and cats with previously diagnosed kidney disease

Figure 5

Scatter plot with line of best fit of results from feline serum and plasma symmetric dimethylarginine (SDMA) concentrations analysed by a commercial laboratory (CL) analyser and point-of-care (POC) analyser prior to optimisation of the CL method (study 1). Note that the individual results are scattered around rather than sitting close to the line of best fit. Note that one very high result (65 μg/dl and 73 μg/dl on each analyser) has been excluded for clarity

Figure 6

Scatter plot with line of best fit of results from feline plasma symmetric dimethylarginine (SDMA) concentrations analysed by a commercial laboratory (CL) analyser and point-of-care (POC) analyser after optimisation of the CL method (study 2). Note that the individual results are scattered around rather than sitting close to the line of best fit

Figure 7

Bland–Altman difference plot for study 1 constructed by plotting for each cat the mean concentration from both analysers (x axis) against the difference between results from each analyser (y axis). The yellow lines indicate the allowable total error (TE_A) as determined by expert opinion (via the survey). The blue sloping lines indicate the desirable total error (TE_D) as determined by a prior biological variation study. The purple lines indicate the limits of agreement (LOA) to 95% confidence interval. The LOA range is approximately double the two determined measures of clinical importance (TE_A and TE_D) and are therefore too high for clinical acceptability

Figure 8

Bland–Altman difference plot for study 2 assessing the mean concentration of each analyser to the difference. The negative bias of the point-of-care (POC) analyser appears to increase as the concentration of symmetric dimethylarginine (SDMA) increases. The limits of agreement (LOA) are very similar to study 1 and too high for clinical acceptability. TEA = allowable total error; TED = desirable total error