title: Ferric citrate controls phosphorus and delivers iron in patients on dialysis.
abstract: Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.
authors: Divisions of Nephrology and Hypertension and Julia.lewis@vanderbilt.edu.
authors: Julia B
authors: JB
authors: Lewis
authors: Divisions of Nephrology and Hypertension and.
authors: Mohammed
authors: M
authors: Sika
authors: Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Mark J
authors: MJ
authors: Koury
authors: Metrolina Nephrology Associates, Charlotte, North Carolina;
authors: Peale
authors: P
authors: Chuang
authors: Divisions of Nephrology and Hypertension and.
authors: Gerald
authors: G
authors: Schulman
authors: Kidney Care Associates, Augusta, Georgia;
authors: Mark T
authors: MT
authors: Smith
authors: Clinical Research Ltd., Canton, Ohio;
authors: Frederick C
authors: FC
authors: Whittier
authors: Nephrology Associates, Nashville, Tennessee;
authors: Douglas R
authors: DR
authors: Linfert
authors: Southeast Renal Research Institute, Chattanooga, Tennessee;
authors: Claude M
authors: CM
authors: Galphin
authors: Pioneer Valley Nephrology, Holyoke, Massachusetts;
authors: Balaji P
authors: BP
authors: Athreya
authors: Washington Nephrology Associates, Bethesda, Maryland;
authors: A Kaldun Kaldun
authors: AK
authors: Nossuli
authors: Western Nephrology, Westminster, Colorado;
authors: Ingrid J
authors: IJ
authors: Chang
authors: Division of Nephrology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors: Samuel S
authors: SS
authors: Blumenthal
authors: Mountain Kidney and Hypertension Associates, Asheville, North Carolina;
authors: John
authors: J
authors: Manley
authors: Pines Clinical Research, Pembroke Pines, Florida;
authors: Steven
authors: S
authors: Zeig
authors: Division of Nephrology and Hypertension, University of Cincinnati, Cincinnati, Ohio;
authors: Kotagal S
authors: KS
authors: Kant
authors: Houston Kidney, Houston, Texas; and.
authors: Juan Jose
authors: JJ
authors: Olivero
authors: Division of Epidemiology, University of Utah, Salt Lake City, Utah.
authors: Tom
authors: T
authors: Greene
authors: Divisions of Nephrology and Hypertension and.
authors: Jamie P
authors: JP
authors: Dwyer
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000378:metabolism / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D006801:Humans; D054559:Hyperphosphatemia / Q000378:metabolism / Q000517:prevention & control; D007501:Iron / Q000378:metabolism*; D007557:Israel; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010758:Phosphorus / Q000378:metabolism*; D006435:Renal Dialysis; D016896:Treatment Outcome; D014481:United States
chemical_list: D005290:Ferric Compounds; D010758:Phosphorus; C025314:ferric citrate; D007501:Iron
keywords: anemia; clinical trial; dialysis; phosphate binders