title: Higher serum direct bilirubin levels were associated with a lower risk of incident chronic kidney disease in middle aged Korean men.
abstract: BACKGROUND
  The association between serum bilirubin levels and incident chronic kidney disease (CKD) in the general population is unknown. We aimed to examine the association between serum bilirubin concentration (total, direct, and indirect) and the risk of incident CKD.
  
  
  RESULTS
  Longitudinal cohort study of 12,823 Korean male workers 30 to 59 years old without CKD or proteinuria at baseline participating in medical health checkup program in a large worksite. Study participants were followed for incident CKD from 2002 through 2011. Estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI equation. CKD was defined as eGFR <60 mL/min per 1.73 m(2). Parametric Cox models and pooled logistic regression models were used to estimate adjusted hazard ratios for incident CKD. We observed 238 incident cases of CKD during 70,515.8 person-years of follow-up. In age-adjusted models, the hazard ratios for CKD comparing quartiles 2-4 vs. quartile 1 of serum direct bilirubin were 0.93 (95% CI 0.67-1.28), 0.88 (0.60-1.27) and 0.60 (0.42-0.88), respectively. In multivariable models, the adjusted hazard ratio for CKD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.60 (95% CI 0.41-0.87; P trend = 0.01). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of CKD.
  
  
  CONCLUSIONS
  Higher serum direct bilirubin levels were significantly associated with a lower risk of developing CKD, even adjusting for a variety of cardiometabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for CKD risk.
authors.affiliation: Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
authors.forename: Seungho
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Department of Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
authors.forename: Hee-Yeon
authors.initials: HY
authors.lastname: Woo
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
authors.forename: Hyosoon
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
authors.forename: Kyu-Beck
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Department of Internal Medicine, Samsung Medical Center, Gangnam-Gu, Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Son
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Department of Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America ; Samsung Comprehensive Cancer Center, Samsung Medical Center, Gangnam-Gu, Seoul, Seoul, Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Department of Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001663:Bilirubin / Q000097:blood*; D015331:Cohort Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors
chemical_list: D001663:Bilirubin