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Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice

  • Mercy Thomas EMAIL logo , Winita Hardikar , Ronda F. Greaves ORCID logo , David G. Tingay , Tze Ping Loh , Vera Ignjatovic , Fiona Newall and Anushi E. Rajapaksa
Published/Copyright: January 15, 2021
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 59 Issue 6

Abstract

Despite a century of research, bilirubin metabolism and the transport mechanisms responsible for homeostasis of bilirubin in serum remain controversial. Emerging evidence on the hepatic membrane transporters and inherited disorders of bilirubin metabolism have contributed to a greater understanding of the various steps involved in bilirubin homeostasis and its associated excretory pathways. We discuss these recent research findings on hepatic membrane transporters and evaluate their significance on the newborn bilirubin metabolism and excretion. New insights gained speculate that a proportion of conjugated bilirubin is excreted via the renal system, as an alternative to the intestinal excretion, even in normal physiological jaundice with no associated pathological concerns. Finally, this paper discusses the clinical relevance of targeting the altered renal excretory pathway, as bilirubin in urine may hold diagnostic importance in screening for neonatal jaundice.

Keywords: bilirubin metabolism; bilirubin – urine; conjugated bilirubin; hepatic membrane transporters; neonatal jaundice; unconjugated bilirubin
Corresponding author: Mercy Thomas, RN RM MSN, New Vaccines, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Newborn Research Centre, Royal Women’s Hospital, Melbourne, Victoria, Australia; Department of Nursing, Royal Children’s Hospital, Melbourne, Victoria, Australia; and Murdoch Children’s Research Institute, The Royal Children’s Hospital 50 Flemington Rd, Parkville, Victoria 3052, Australia, E-mail:

Funding source: National Health and Medical Research Council (NHMRC)

Award Identifier / Grant number: GNT1139340

Funding source: Victorian Government Operational Infrastructure Support Program

Funding source: NHMRC Early Career Fellowship

Award Identifier / Grant number: GNT1123030

Funding source: University of Melbourne

Funding source: National Health and Medical Research Council Clinical Career Development Fellowship

Award Identifier / Grant number: 1053889

Acknowledgments

The authors wish to thank Mr Blake D’Souza for his support in drawings of bilirubin metabolism (Figure 1).

  1. Research funding: This study is supported by a National Health and Medical Research Council (NHMRC) Development Grant (GNT1139340) and the Victorian Government Operational Infrastructure Support Program (Melbourne, Australia). AER is supported by an NHMRC Early Career Fellowship (GNT1123030). MT is supported by an RTP scholarship governed by the University of Melbourne. DGT is supported by a National Health and Medical Research Council Clinical Career Development Fellowship (Grant ID 1053889).

  2. Author contributions: MT and AER developed the concept of the manuscript. MT prepared the first draft under the supervision of AER and RG. WH and DT contributed their expertise in hepatology and neonatology, respectively, in reviewing the manuscript. TPL contributed his expertise in reviewing the clinical chemistry of bilirubin and overall structure of the manuscript. MT reviewed and screened the included references. All authors contributed to the re-drafting of the manuscript.

  3. Competing interests: None of the authors have any financial interests or conflicts of interest to declare. The members of the team are involved in the development of a method of detecting jaundice in neonates using a urine-based testing system.

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Received: 2020-11-26
Accepted: 2020-12-22
Published Online: 2021-01-15
Published in Print: 2021-05-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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  2. Editorial
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  4. Review
  5. Global FT4 immunoassay standardization: an expert opinion review
  6. Mini Review
  7. Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice
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  42. Congress Abstract
  43. 12th National Scientific Congress SPML,29–31 October 2020, Online, Portugal
https://doi.org/10.1515/cclm-2020-1759
Keywords for this article
bilirubin metabolism; bilirubin – urine; conjugated bilirubin; hepatic membrane transporters; neonatal jaundice; unconjugated bilirubin

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. COVID-19: which lessons have we learned?
  4. Review
  5. Global FT4 immunoassay standardization: an expert opinion review
  6. Mini Review
  7. Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice
  8. Opinion Paper
  9. Laboratory medicine in the COVID-19 era: six lessons for the future
  10. EFLM Paper
  11. How to meet ISO15189:2012 pre-analytical requirements in clinical laboratories? A consensus document by the EFLM WG-PRE
  12. General Clinical Chemistry and Laboratory Medicine
  13. External quality assessment of M-protein diagnostics: a realistic impression of the accuracy and precision of M-protein quantification
  14. Error simulation modeling to assess the effects of bias and precision on bilirubin measurements used to screen for neonatal hyperbilirubinemia
  15. NT-proBNP levels in preeclampsia, intrauterine growth restriction as well as in the prediction on an imminent delivery
  16. Serum N-glycan fingerprint nomogram predicts liver fibrosis: a multicenter study
  17. Hematology and Coagulation
  18. Performance of digital morphology analyzer Vision Pro on white blood cell differentials
  19. Cardiovascular Diseases
  20. Prognostic implication of elevated cardiac troponin I in patients visiting emergency department without diagnosis of coronary artery disease
  21. Relationships between renal function variations and relative changes in cardiac troponin T concentrations based on quantile generalized additive models (qgam)
  22. Diabetes
  23. Association of hemoglobin H (HbH) disease with hemoglobin A1c and glycated albumin in diabetic and non-diabetic patients
  24. Comparative study of i-SENS glucometers in neonates using capillary blood samples
  25. Infectious Diseases
  26. Evaluation of four commercial, fully automated SARS-CoV-2 antibody tests suggests a revision of the Siemens SARS-CoV-2 IgG assay
  27. Vitamin-D levels and intensive care unit outcomes of a cohort of critically ill COVID-19 patients
  28. Does mid-regional pro-adrenomedullin (MR-proADM) improve the sequential organ failure assessment-score (SOFA score) for mortality-prediction in patients with acute infections? Results of a prospective observational study
  29. Letters to the Editors
  30. Global FT4 immunoassay standardization. Response to: Kratzsch J et al. Global FT4 immunoassay standardization: an expert opinion review
  31. Free-thyroxine standardization: waiting for Godot while well serving our patients today
  32. Prevalence of SARS-CoV-2 antibodies in health care personnel of two acute care hospitals in Linz, Austria
  33. Pediatric evaluation of clinical specificity and sensitivity of SARS-CoV-2 IgG and IgM serology assays
  34. Prevention and control of COVID-19 in the penitentiary of Florence
  35. Pooling for SARS-CoV-2-testing: comparison of three commercially available RT-qPCR kits in an experimental approach
  36. Very high SARS-CoV-2 load at the emergency department presentation strongly predicts the risk of admission to the intensive care unit and death
  37. Next-generation sequencing and RT-PCR to identify a 32-day SARS-CoV-2 carrier
  38. 25-Hydroxyvitamin D concentrations in COVID-19 patients hospitalized in intensive care unit during the first wave and the second wave of the pandemic
  39. Laboratory findings in a child with SARS-CoV-2 (COVID-19) multisystem inflammatory syndrome
  40. Discrepant cardiac troponin results in a young woman
  41. Response to: towards the rational utilization of SARS-CoV-2 serological tests in clinical practice
  42. Congress Abstract
  43. 12th National Scientific Congress SPML,29–31 October 2020, Online, Portugal
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