Interference of ketone bodies on laboratory creatinine measurement in children with DKA: a call for change in testing
Damian Feldman-Kiss1, Dailin Li2,3, Richard Cleve3,4
1Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC, Canada.
Insights
Ketone bodies interfere with creatinine measurements, particularly with Jaffe methods in children with diabetic ketoacidosis. Standardizing to enzymatic methods is recommended for accurate pediatric kidney function assessment.
Area of Science:
- Clinical Chemistry
- Pediatric Nephrology
- Biochemical Analysis
Background:
- Ketone bodies (KBs) are known to interfere with creatinine (Cr) assays.
- Diabetic ketoacidosis (DKA) patients, especially children, have a high incidence of acute kidney injury (AKI).
- The impact of KB interference on pediatric Cr measurement accuracy in AKI assessment is unclear.
Purpose of the Study:
- To investigate the interference of ketone bodies on creatinine measurements in pediatric samples.
- To compare the accuracy of enzymatic and Jaffe methods for creatinine measurement in the presence of ketone bodies.
- To assess the clinical implications for diagnosing acute kidney injury in children with diabetic ketoacidosis.
Main Methods:
- Pooled plasma samples with three creatinine levels were spiked with acetone, acetoacetate, and β-hydroxybutyrate.
- Creatinine concentrations were measured using two enzymatic (E1, E2) and two Jaffe (J1, J2) methods.
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) served as the gold standard for comparison.
Main Results:
- Enzymatic methods (E1, E2) showed no interference from any ketone bodies.
- Jaffe methods (J1, J2) were unaffected by β-hydroxybutyrate.
- Acetone caused dose-dependent positive interference in both Jaffe methods.
- Acetoacetate caused dose-dependent positive interference in J1 and negative interference in J2.
Conclusions:
- Jaffe methods are significantly more susceptible to interference from acetone and acetoacetate than enzymatic methods, especially at low creatinine levels common in pediatrics.
- Method-specific biases can lead to ambiguous interpretation of kidney function in DKA patients.
- Standardization to enzymatic creatinine assays is recommended to improve DKA patient care and accurate AKI assessment.
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. A higher resolution version of the Graphical abstract is available as Supplementary information.
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