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When results matter: reliable creatinine concentrations in hyperbilirubinemia patients

  • Roseri J.A.C. Roelofsen-de Beer , Bertrand D. van Zelst , Aram B. Vroling , Yolanda B. de Rijke and Christian Ramakers EMAIL logo
Published/Copyright: November 29, 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 57 Issue 5

Abstract

Background

Failure to report a creatinine concentration, especially in icteric patients who are eligible for a liver transplant, can result in a life-threatening situation. We assessed the influence of bilirubin interference on several creatinine assays and investigated ways to circumvent icteric interference without interfering with our normal automated sample logistics.

Methods

Using icteric patient sera (total bilirubin >255 μmol/L) we determined creatinine concentrations using an enzymatic and Jaffé assay (Roche Diagnostics) in both normal (i.e. undiluted) and decreased mode (i.e. diluted) as well as an enzyme-coupled amperometric assay on a Radiometer ABL837 FLEX analyzer. Creatinine concentrations from the five methods were compared with an in-house developed LC-MS/MS method. Passing and Bablok (proportional and constant bias) as well as difference plot parameters (bias and 95% limits of agreement [LoA]) were calculated. Interferograph-based regression analysis of the enzymatic and Jaffé results was used to investigate if such an approach could be used to report corrected creatinine concentrations in icteric patient sera.

Results

In icteric patient sera the enzyme-coupled amperometric assay was hardly influenced by icteric interference as shown by a difference plot bias of −1.5% (95% LoA −11.6 to +8.5%). The undiluted Jaffé method had a bias of −1.4% with a very broad 95% LoA (−35.1 to +32.2%) emphasizing the poor specificity of this method. The undiluted enzymatic method had the largest bias (−13.4%, 95% LoA −35.8 to +9.0%). Diluting sera in the enzymatic method did not improve the bias (−10.5%, 95% LoA −25.4 to 4.4%), while diluting the Jaffé method resulted in a bias increase (+11.4%, 95% LoA −14.7 to 37.5%). Using interferograph-based regression analysis we were able to reliably correct enzymatic creatinine concentrations in 97 out of 100 icteric patient sera.

Conclusions

Analytically, quantifying creatinine in icteric sera using the Radiometer ABL837 FLEX analyzer is the method of choice within our laboratory. However, not all laboratories are equipped with this method and even if available, the limited number of highly icteric patient sera makes this method costly. For those laboratories using the Roche enzymatic method, mathematically correcting an icteric creatinine concentration using an interferograph based on an LC-MS/MS reference method is a suitable alternative to report reliable creatinine results in icteric patients.

Keywords: amperometric; creatinine; enzymatic; hyperbilirubinemia; Jaffé; LC-MS/MS
Corresponding author: Dr. Christian Ramakers, Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands, Phone: +31107041602, Fax: +31104367894

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-0959).

Received: 2018-08-31
Accepted: 2018-10-01
Published Online: 2018-11-29
Published in Print: 2019-04-24

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2018-0959
Keywords for this article
amperometric; creatinine; enzymatic; hyperbilirubinemia; Jaffé; LC-MS/MS

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Cardiac biomarkers – 2019
  4. Reviews
  5. Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice
  6. Serum cytokines, adipokines and ferritin for non-invasive assessment of liver fibrosis in chronic liver disease: a systematic review
  7. Opinion Papers
  8. Detection capability of quantitative faecal immunochemical tests for haemoglobin (FIT) and reporting of low faecal haemoglobin concentrations
  9. Should phosphatidylethanol be currently analysed using whole blood, dried blood spots or both?
  10. IFCC Papers
  11. High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers
  12. Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB)
  13. Genetics and Molecular Diagnostics
  14. Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation
  15. General Clinical Chemistry and Laboratory Medicine
  16. Commutable whole blood reference materials for hemoglobin A1c validated on multiple clinical analyzers
  17. When results matter: reliable creatinine concentrations in hyperbilirubinemia patients
  18. Mass spectrometry based analytical quality assessment of serum and plasma specimens with patterns of endo- and exogenous peptides
  19. Association of serum sphingomyelin profile with clinical outcomes in patients with lower respiratory tract infections: results of an observational, prospective 6-year follow-up study
  20. Effect of an activated charcoal product (DOAC Stop™) intended for extracting DOACs on various other APTT-prolonging anticoagulants
  21. Hematology and Coagulation
  22. Commutability assessment of reference materials for the enumeration of lymphocyte subsets
  23. Circulating platelet-neutrophil aggregates as risk factor for deep venous thrombosis
  24. Reference Values and Biological Variations
  25. A comparison of complete blood count reference intervals in healthy elderly vs. younger Korean adults: a large population study
  26. Indirect determination of hematology reference intervals in adult patients on Beckman Coulter UniCell DxH 800 and Abbott CELL-DYN Sapphire devices
  27. Cancer Diagnostics
  28. Large platelet size is associated with poor outcome in patients with metastatic pancreatic cancer
  29. Cardiovascular Diseases
  30. Sample matrix and high-sensitivity cardiac troponin I assays
  31. Preoperative proteinuria and clinical outcomes in type B aortic dissection after thoracic endovascular aortic repair
  32. Infectious Diseases
  33. The rational specimen for the quantitative detection of Epstein-Barr virus DNA load
  34. Letters to the Editor
  35. Letter to the Editor on article Dimech W, Karakaltsas M, Vincini G. Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing. Clin Chem Lab Med 2018;56:1970–8
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