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Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis
BACKGROUND: Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. METHODS: We assessed a prospective cohort with a reference range of total bilirubin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321406/ https://www.ncbi.nlm.nih.gov/pubmed/28225832 http://dx.doi.org/10.1371/journal.pone.0172434 |
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author | Park, Sehoon Kim, Do Hyoung Hwang, Jin Ho Kim, Yong-Chul Kim, Jin Hyuk Lim, Chun Soo Kim, Yon Su Yang, Seung Hee Lee, Jung Pyo |
author_facet | Park, Sehoon Kim, Do Hyoung Hwang, Jin Ho Kim, Yong-Chul Kim, Jin Hyuk Lim, Chun Soo Kim, Yon Su Yang, Seung Hee Lee, Jung Pyo |
author_sort | Park, Sehoon |
collection | PubMed |
description | BACKGROUND: Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. METHODS: We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. RESULTS: As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8–1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19–0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). CONCLUSIONS: Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression. |
format | Online Article Text |
id | pubmed-5321406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53214062017-03-09 Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis Park, Sehoon Kim, Do Hyoung Hwang, Jin Ho Kim, Yong-Chul Kim, Jin Hyuk Lim, Chun Soo Kim, Yon Su Yang, Seung Hee Lee, Jung Pyo PLoS One Research Article BACKGROUND: Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. METHODS: We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. RESULTS: As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8–1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19–0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). CONCLUSIONS: Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression. Public Library of Science 2017-02-22 /pmc/articles/PMC5321406/ /pubmed/28225832 http://dx.doi.org/10.1371/journal.pone.0172434 Text en © 2017 Park et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Park, Sehoon Kim, Do Hyoung Hwang, Jin Ho Kim, Yong-Chul Kim, Jin Hyuk Lim, Chun Soo Kim, Yon Su Yang, Seung Hee Lee, Jung Pyo Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis |
title | Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis |
title_full | Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis |
title_fullStr | Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis |
title_full_unstemmed | Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis |
title_short | Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis |
title_sort | elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321406/ https://www.ncbi.nlm.nih.gov/pubmed/28225832 http://dx.doi.org/10.1371/journal.pone.0172434 |
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