title: Association of serum total bilirubin with renal outcome in Japanese patients with stages 3-5 chronic kidney disease.
abstract: OBJECTIVE
  Serum bilirubin has been reported to be associated with the progression of kidney disease in patients with diabetic nephropathy. Less is known, however, about the relationship between bilirubin and chronic kidney disease (CKD) of other etiologies. This study was designed to clarify whether serum total bilirubin concentration is associated with kidney disease progression in patients with CKD independent of etiology.
  
  
  METHODS
  This prospective observational study enrolled 279 consecutive patients with stages 3-5 CKD. The renal endpoint was the composite of the doubling of serum creatinine or end-stage renal disease requiring dialysis. Patients were divided into three groups by their serum total bilirubin concentrations: ≤0.3 (lowest), 0.4-0.5 (middle), and ≥0.6 (highest) mg/dL. A Cox proportional hazards model was applied to determine the risk factors for poor renal outcome.
  
  
  RESULTS
  The median follow-up period was 21months. One-hundred and three patients reached renal end points. After multivariable adjustment, a 0.1mg/dL increase in serum bilirubin was associated negatively with poor renal outcome (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.87). In addition, after adjustment for confounding factors, including traditional and nontraditional cardiovascular risk factors, the middle (HR 3.14, 95% CI 1.36-8.57) and lowest (HR 4.22, 95% CI 1.81-11.59) bilirubin groups had significantly higher HRs for renal outcome than the highest bilirubin group.
  
  
  CONCLUSIONS
  Lower serum bilirubin concentration was independently associated with adverse renal outcomes, suggesting that the measurement of serum bilirubin is useful for predicting kidney disease progression in patients with moderate to severe CKD.
authors.affiliation: Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center Hospital, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Sakoh
authors.affiliation: Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center Hospital, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan. Electronic address: mnaka@kyumed.jp.
authors.forename: Masaru
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Yoshitomi
authors.affiliation: Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center Hospital, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Ura
authors.affiliation: Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center Hospital, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nishimoto
authors.affiliation: Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center Hospital, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Fukui
authors.affiliation: Division of Nephrology and Clinical Research Institute, Department of Internal Medicine, National Kyushu Medical Center Hospital, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Shikuwa
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsuruya
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001663:Bilirubin / Q000097:blood*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D003404:Creatinine; D001663:Bilirubin
keywords: Chronic kidney disease; Oxidative stress; Renal outcome; Serum bilirubin