title: ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD) Patients, But Not with Iron Storage.
abstract: OBJECTIVE
  It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA.
  
  
  METHODS
  We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI).
  
  
  RESULTS
  A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level.
  
  
  CONCLUSIONS
  Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.
authors.affiliation: Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuragano
authors.affiliation: The Third Department of Internal Medicine Faculty of Medicine, The University of Yamanashi, Chuo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitamura
authors.affiliation: Department of Nephrology and Blood Purification, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsumura
authors.affiliation: Department of Nephrology and Blood Purification, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kida, Japan.
authors.forename: Taiga
authors.initials: T
authors.lastname: Hara
authors.affiliation: Division of Integrated Nephrology and Telemedicine, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kiyomoto
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Fujimoto
authors.affiliation: Department of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hase
authors.affiliation: Department of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Joki
authors.affiliation: Department of Internal Medicine, Yachiyo Hospital, Anjyo, Japan.
authors.forename: Atushi
authors.initials: A
authors.lastname: Fukatsu
authors.affiliation: Department of Internal Medicine, Higashikouri Hospital, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Internal Medicine, Itakura Clinic, Tokorozawa, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Itakura
authors.affiliation: Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
mesh_terms: D000368:Aged; D005260:Female; D005293:Ferritins / Q000097:blood; D006397:Hematinics / Q000009:adverse effects* / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014168:Transferrin / Q000378:metabolism
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D014168:Transferrin; D005293:Ferritins; D007501:Iron