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Kidney Int. 2014 Oct;86(4):845-54. doi: 10.1038/ki.2014.114. Epub 2014 Apr 23.

Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients.

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Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Department of Internal Medicine, Musashi Ranzan Hospital, Ranzan, Japan.
Department of Nephrology and Blood Purification, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Division of Integrated Nephrology and Telemedicine, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan.
Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Department of Nephrology, Toho University, Ohashi Medical Center, Tokyo, Japan.
Department of Internal Medicine, Yachiyo Hospital, Aichi, Japan.
Department of Internal Medicine, Higashikouri Hospital, Higashikouri, Japan.
Department of Internal Medicine, Itakura Clinic, Saitama, Japan.


In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations.

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