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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

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.


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

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