title: Time-dependent resistance to erythropoiesis-stimulating agent and mortality in hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study.
abstract: OBJECTIVE
  Resistance to erythropoiesis-stimulating agent (ESA) is associated with mortality in hemodialysis (HD) patients. Time-dependent variability of ESA resistance has been not investigated adequately, although consistently high ESA resistance is expected to be a high risk for mortality. Our aim, therefore, was to investigate consistently high ESA resistance as an independent predictor of mortality in HD patients.
  
  
  METHODS
  This study evaluated 2,104 Japanese HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) III. ESA resistance index (ERI) was defined as the weekly weight-adjusted dose of ESA divided by hemoglobin concentration. The average ERI was calculated from ERI levels every 4 months throughout the observation period for each patient. To assess the size of the fluctuation in average ERI during the observation periods according to ERI quartiles at the enrollment periods, six patient groups were defined on the basis of patterns of ERI level fluctuation: low-low (Low), intermediate-intermediate (Intermediate), high-high (High), low-intermediate, intermediate-high, and low-high.
  
  
  RESULTS
  The number of deaths among the patients was 227 (10.8%), which included 113 (5.4%) cases of cardiovascular disease (CVD). In multivariate analysis after adjustment for age, albumin, C-reactive protein, comorbidities, etc., the High group was independently and significantly related to all-cause and CVD-related mortality (OR = 2.33, 95% CI: 1.33-4.07, p = 0.002, and OR = 2.09, 95% CI: 1.05-4.14, p = 0.035, respectively).
  
  
  CONCLUSIONS
  Factoring out fluctuating ERI increases the ability of consistently high ERI levels as an independent risk factor for all-cause and CVD mortality in HD patients.
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama Minami Kyosai Hospital, Yokohama, Japan. tftf @ yokohama-cu.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiba
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
mesh_terms: D002318:Cardiovascular Diseases / Q000401:mortality*; D004351:Drug Resistance; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D006397:Hematinics