Methodology-related pseudohyperkalemia associated with marked muscle enzyme leakage in a dog

As hyperkalemia may be life-threatening, it is critical to recognize artifactually increased potassium concentrations. Pseudohyperkalemia may occur in myopathies when using the VetScan2 analyzer (VS2), but the degree of pseudohyperkalemia and relationships relative to creatine kinase activity (CK) are unknown.

We aimed to determine what degree of muscle enzyme leakage, as reflected by increased serum CK activity, results in cases with falsely elevated potassium concentrations when measured by the VS2. We also sought to establish if a linear relationship exists between potassium concentrations measured by the VS2 and CK activity.

Serum samples from dogs with increased CK activity and with CK activity within the reference interval and without clinically relevant biochemical alterations were used to create diluted samples having various CK activities. Potassium concentrations and CK activities were determined on VS2 and Cobas c501 (Cobas) analyzers. Wilcoxon signed rank, Bland-Altman, and Passing-Bablok analyses were used to compare potassium concentrations generated by the VS2 and Cobas analyzers. Least squares regression analysis was performed to evaluate if a linear relationship exists between VS2 potassium concentrations and Cobas CK activities.

Potassium concentrations from the VS2 were higher (median and standard deviation (SD) = 5.2 +/- 0.46 mmol/L) than those from the Cobas analyzer (4.4 +/- 0.35 mmol/L; P < 0.000), and a positive mean bias was found (mean difference = 0.774 mmol/L; 95% Confidence Interval (CI) = 0.706-0.842; limits of agreement = 0.21-1.34). Passing-Bablok regression showed a positive proportional bias for potassium concentrations on the VS2 compared with paired Cobas results (Slope = 1.328; 95% CI = 1.100-1.500) but did not reveal systematic bias (Intercept = -0.714; 95% CI = -1.46-0.265). Least squares regression analysis showed a poor non-significant relationship (R²  = 0.19) between potassium measured by the VS2 and CK measured by the Cobas analyzer.

A defined threshold value of CK activity at which potassium concentration begins to falsely increase when measured on the VS2 was not established as data widely varied. A poor non-significant relationship between potassium concentrations and CK activities did not allow prediction of the threshold at which falsely increased potassium concentrations would be expected on the VS2.