title: Both low and high serum ferritin levels predict mortality risk in hemodialysis patients without inflammation.
abstract: BACKGROUND
  Serum ferritin concentration >100 ng/mL was associated with a higher risk of death in hemodialysis patients in Japan, whereas such an association was less clear in hemodialysis patients in Western countries. Since Japanese dialysis patients are generally less inflamed than those in Western countries, inflammation may modify the association between serum ferritin and the adverse outcomes.
  
  
  METHODS
  We performed an observational cohort study using data from 2606 Japanese hemodialysis patients who participated in the Dialysis Outcomes and Practice Patterns Study (DOPPS) III (2005-2008) or DOPPS IV (2009-2012). The predictor was serum ferritin category (<50, 50-99.9, 100-199.9, and ≥200 ng/mL), and the primary and secondary outcomes were all-cause mortality and cardiovascular hospitalization, respectively. C-reactive protein (CRP, cut-off by 0.3 mg/dL) and serum albumin (cut-off by 3.8 g/dL) were stratification factors related to systemic inflammation.
  
  
  RESULTS
  After adjustment for relevant confounding factors, a U-shaped association was observed between serum ferritin and all-cause mortality in the group with low CRP levels, whereas such relationship was not significant in the high CRP counterparts. In contrast, we found a linear association between serum ferritin and cardiovascular hospitalization in the low CRP and high CRP groups commonly. Similar results were obtained when the total cohort was stratified by serum albumin.
  
  
  CONCLUSIONS
  Serum ferritin showed different patterns of association with all-cause mortality in hemodialysis patients with versus without inflammation, whereas its association with cardiovascular hospitalization was similar regardless of inflammatory conditions.
authors: Department of Vascular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. t-shoji@med.osaka-cu.ac.jp.
authors: Tetsuo
authors: T
authors: Shoji
authors: Institute for Health Outcomes and Process Evaluation research (iHope International), Kyoto, Japan.|Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University, Fukushima, Japan.
authors: Kakuya
authors: K
authors: Niihata
authors: Institute for Health Outcomes and Process Evaluation research (iHope International), Kyoto, Japan.|Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Shingo
authors: S
authors: Fukuma
authors: Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University, Fukushima, Japan.|Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Shunichi
authors: S
authors: Fukuhara
authors: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors: Tadao
authors: T
authors: Akizawa
authors: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Masaaki
authors: M
authors: Inaba
mesh_terms: D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death; D015536:Down-Regulation; D005260:Female; D005293:Ferritins / Q000032:analysis*; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000401:mortality*; D007564:Japan; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality*; D012307:Risk Factors; D000075462:Serum Albumin, Human / Q000032:analysis; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: C422455:ALB protein, human; D015415:Biomarkers; D002097:C-Reactive Protein; D005293:Ferritins; D000075462:Serum Albumin, Human
keywords: Cardiovascular disease (CVD); Cohort; Ferritin; Hemodialysis; Mortality