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

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Abstract

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.

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Data availability

Available.

Code availability

Not applicable.

Abbreviations

DKA:

Diabetic ketoacidosis

DM:

Diabetes mellitus

KB:

Ketone bodies

Ac:

Acetone

AA:

Acetoacetate

β-OHB:

β-Hydroxybutyrate

AKI:

Acute kidney injury

Cr:

Serum creatinine

LC–MS/MS:

Liquid chromatography-tandem mass spectrometry

E1:

Ortho VITROS® 5600

E2:

Roche cobas® C501

J1:

Beckman Coulter UniCel DxC 800

J2:

Siemens VISTA® 1500

KDIGO:

The Kidney Disease: Improving Global Outcomes

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Acknowledgements

The authors wish to thank Drs. Peter Skippen and Niranjan Kissoon from the Department of Pediatrics at the University of British Columbia for reviewing the manuscript, and Dr. David Seccombe from CEQAL for providing the regional Cr methodology survey data.

Funding

Damian Feldman-Kiss was awarded funding by the Summer Student Research Program, Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, to conduct this research project.

Author information

Authors and Affiliations

  1. Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC, Canada

    Damian Feldman-Kiss

  2. Vancouver General Hospital, Vancouver, BC, Canada

    Dailin Li

  3. Dept of Pathology and Laboratory Medicine, BC Children’s & Women’s Hospital, University of British Columbia, 4480 Oak Street, Room 2J9, Vancouver, BC, V6H 3N1, Canada

    Dailin Li, Richard Cleve, Graham Sinclair, Joshua A. Dubland & Li Wang

  4. Surrey Memorial Hospital, Surrey, BC, Canada

    Richard Cleve

  5. BC Children’s Hospital, Vancouver, BC, Canada

    Graham Sinclair, Joshua A. Dubland & Li Wang

  6. BC Children’s Hospital Research Institute, Vancouver, BC, Canada

    Graham Sinclair, Joshua A. Dubland & Li Wang

Authors
  1. Damian Feldman-Kiss
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  2. Dailin Li
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  3. Richard Cleve
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  4. Graham Sinclair
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  5. Joshua A. Dubland
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  6. Li Wang
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Contributions

Dr. Wang conceptualized and designed the study (principal investigator). All the authors contributed to data acquisition, analysis, and interpretation. Statistical analysis was performed by Mr. Feldman-Kiss and Dr. Dubland. Mr. Feldman-Kiss, Dr. Dubland, and Dr. Wang drafted the manuscript. All the authors contributed to critical revisions of the manuscript for intellectual content and agreed to be guarantors of the work. Administrative, technical, and material support was provided by Drs. Dubland, Li, Sinclair, and Cleve.

Corresponding author

Correspondence to Li Wang.

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Feldman-Kiss, D., Li, D., Cleve, R. et al. Interference of ketone bodies on laboratory creatinine measurement in children with DKA: a call for change in testing practices. Pediatr Nephrol 37, 1347–1353 (2022). https://doi.org/10.1007/s00467-021-05324-0

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  • DOI: https://doi.org/10.1007/s00467-021-05324-0

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