title: A randomized trial of intravenous and oral iron in chronic kidney disease.
abstract: Although iron is commonly used to correct iron deficiency anemia (IDA) in chronic kidney disease (CKD), its effect on kidney function is unclear. To assess this, we randomly assigned patients with stage 3 and 4 CKD and IDA to either open-label oral ferrous sulfate (69 patients to 325 mg three times daily for 8 weeks) or intravenous iron sucrose (67 patients to 200 mg every 2 weeks, total 1 g). The primary outcome was the between-group difference in slope of measured glomerular filtration rate (mGFR) change over two years. The trial was terminated early on the recommendation of an independent data and safety monitoring board based on little chance of finding differences in mGFR slopes, but a higher risk of serious adverse events in the intravenous iron treatment group. mGFR declined similarly over two years in both treatment groups (oral -3.6 ml/min per 1.73 m(2), intravenous -4.0 ml/min per 1.73 m(2), between-group difference -0.35 ml/min per 1.73 m(2); 95% confidence interval -2.9 to 2.3). There were 36 serious cardiovascular events among 19 participants assigned to the oral iron treatment group and 55 events among 17 participants of the intravenous iron group (adjusted incidence rate ratio 2.51 (1.56-4.04)). Infections resulting in hospitalizations had a significant adjusted incidence rate ratio of 2.12 (1.24-3.64). Thus, among non-dialyzed patients with CKD and IDA, intravenous iron therapy is associated with an increased risk of serious adverse events, including those from cardiovascular causes and infectious diseases.
authors.affiliation: Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.affiliation: Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Pappas
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D057239:Early Termination of Clinical Trials; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077605:Ferric Oxide, Saccharated; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005937:Glucaric Acid / Q000008:administration & dosage* / Q000009:adverse effects; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007196:Indiana; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005290:Ferric Compounds; D005296:Ferrous Compounds; D006397:Hematinics; D006454:Hemoglobins; C020748:ferrous sulfate; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid