title: Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy.
abstract: BACKGROUND
  Serum bilirubin has been recognized as a novel endogenous antioxidant. The aim of our study was to evaluate the impact of serum bilirubin on kidney prognosis in IgA nephropathy (IgAN).
  
  
  METHODS
  We followed retrospectively 694 patients with IgAN diagnosed by renal biopsy between 1982 and 2010. The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazard model. Predictive performance between models with or without serum bilirubin was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI).
  
  
  RESULTS
  Seventy-seven patients developed ESRD during the median 4.9 years of follow-up. Estimated glomerular filtration rate, proteinuria and histological severity were inversely related to bilirubin levels. In multivariate analysis, serum bilirubin was an independent risk factor for ESRD (hazard ratio for every 0.1 mg/dL decrease in serum bilirubin, 1.18; 95 % CI, 1.04-1.33). The incidence rate of ESRD decreased linearly with the increases in bilirubin levels (P for trend <0.01). When bilirubin was incorporated into a model with conventional ESRD risk factors, the NRI and IDI were 0.281 (P = 0.02) and 0.019 (P = 0.01), respectively.
  
  
  CONCLUSIONS
  We demonstrated that lower bilirubin levels were significantly associated with higher risk of ESRD in IgAN. In addition, bilirubin provided incremental predictive value in the risk assessment for progression of IgAN beyond that provided by standard risk factors.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 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, Fukuoka, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Masutani
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nagata
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuchimoto
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. tsuruya@intmed2.med.kyushu-u.ac.jp.|Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. tsuruya@intmed2.med.kyushu-u.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsuruya
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood*; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011507:Proteinuria / Q000652:urine; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D001663:Bilirubin
keywords: Bilirubin; IgA nephropathy; Oxidative stress; Risk reclassification