title: Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sehoon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.
authors.forename: Do Hyoung
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Hyuk
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.|Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chun Soo
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.|Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Pyo
authors.initials: JP
authors.lastname: Lee
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001663:Bilirubin / Q000097:blood* / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D014517:Ureteral Obstruction / Q000097:blood / Q000473:pathology / Q000503:physiopathology
chemical_list: D003404:Creatinine; D001663:Bilirubin