title: A prospective observational study of early intervention with erythropoietin therapy and renal survival in non-dialysis chronic kidney disease patients with anemia: JET-STREAM Study.
abstract: BACKGROUND
  There is limited data showing that early treatment for anemia could prolong renal survival in non-dialysis chronic kidney disease (CKD) patients. We therefore investigated the relationship between hemoglobin (Hb) levels at initiation of epoetin beta therapy and renal outcome in non-dialysis CKD patients with anemia.
  
  
  METHODS
  In this prospective, multi-center, observational study, non-dialysis CKD patients with anemia who were naïve to erythropoiesis-stimulating agents (ESAs) were divided into three groups based on their Hb levels at initiation of epoetin beta therapy (Group I: 10 ≤ Hb < 11 g/dL, Group II: 9 ≤ Hb < 10 g/dL, and Group III: Hb < 9 g/dL). The primary endpoint was time to first occurrence of any renal event. For the primary analysis, an inverse probability weighted Cox regression model was used to adjust time-dependent selection bias in the artificially censored data.
  
  
  RESULTS
  A total of 1113 patients were eligible for primary endpoint analysis. Risk of renal events was significantly higher in Group III compared with Group I (HR, 2.52; 95 % CI, 1.98-3.21; P < 0.0001); although not significant, the risk was also higher in Group II compared with Group I (HR, 1.48; 95 % CI, 0.91-2.40; P = 0.11).
  
  
  CONCLUSIONS
  Initiation of ESA therapy when Hb levels decreased below 11 g/dL but not below 10 g/dL could be more effective at reducing the risk of renal events in non-dialysis CKD patients with anemia compared with initiation of ESA therapy at below 9 g/dL or even 10 g/dL.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
authors.affiliation: Course of Safety Management in Health Care Sciences, Graduate School of Health Care Sciences, Jikei Institute, Osaka, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubakihara
authors.affiliation: Division of Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hirakata
authors.affiliation: Department of Internal Medicine, Kasugai Municipal Hospital, Nagoya, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hase
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishi
authors.affiliation: Division of Nephrology and Hypertension, Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Babazono
authors.affiliation: Pharmacovigilance Department, Chugai Pharmaceutical Co. Ltd., 2-1-1 Nihonbashi-Muromachi, Chuo-ku, Tokyo, 103-8324, Japan. ishikawamck@chugai-pharm.co.jp.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kumagai
authors.affiliation: Pharmacovigilance Department, Chugai Pharmaceutical Co. Ltd., 2-1-1 Nihonbashi-Muromachi, Chuo-ku, Tokyo, 103-8324, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Katakura
authors.affiliation: Biostatistics Division, Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy*; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications*
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin
keywords: Anemia; Chronic kidney disease; Erythropoiesis-stimulating agents; Non-dialysis; Renal survival