Interference of ketone bodies on laboratory creatinine measurement in children with DKA: a call for change in testing practices

Background The presence of ketone bodies (KBs) can interfere with creatinine (Cr) measurement in both enzymatic and Jaffe methods. Since a high proportion of children hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), here we investigate whether KB interferences affect the accuracy of pediatric Cr measurement. Methods Residual patient plasma samples were pooled to make three Cr levels (~ 50, 100, and 250 μM). KBs (acetone, acetoacetate, and β-hydroxybutyrate) were used to spike the pooled samples. All samples were measured for Cr by two enzymatic methods (E1 and E2), two Jaffe methods (J1 and J2), and LC–MS/MS. LC–MS/MS was considered the gold standard, and the % difference in Cr concentration was calculated for each method. Results E1 and E2 were unaffected by the presence of all three KBs. J1 and J2 were unaffected by the presence of β-hydroxybutyrate. The presence of acetone resulted in dose-dependent positive interference in both Jaffe methods, whereas the presence of acetoacetate resulted in dose-dependent positive and negative interference in J1 and J2, respectively. Conclusions Compared to the enzymatic methods, the Jaffe methods were much more susceptible to interference by acetone and acetoacetate, especially at lower Cr values which are commonly seen in pediatrics. Interpretation of changes in Cr concentration between different hospitals when transferring patients can become ambiguous and true kidney function unclear if different methods are used without awareness of method-specific biases. To improve DKA patient care, we recommend standardizing all of the Cr methods to an enzymatic method. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information