title: A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD Stages 3-5.
abstract: BACKGROUND
  Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality.
  
  
  METHODS
  Double-blind, placebo-controlled, randomized trial.
  
  
  METHODS
  149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2), iron deficiency anemia (hemoglobin, 9.0-12.0 g/dL; transferrin saturation [TSAT]≤ 30%, serum ferritin ≤ 300 ng/mL), and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited.
  
  
  METHODS
  Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo.
  
  
  METHODS
  Coprimary end points were change in TSAT and serum phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary phosphate excretion, and estimated glomerular filtration rate.
  
  
  RESULTS
  Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum phosphate level (4.7 ± 0.6 to 4.4 ± 0.8 mg/dL; between-group P<0.001 for each). Ferric citrate increased hemoglobin levels (from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL; P<0.001 vs placebo), reduced urinary phosphate excretion 39% (P<0.001 vs placebo), and reduced serum intact FGF-23 levels from a median of 159 (IQR, 102-289) to 105 (IQR, 65-187) pg/mL (P=0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms.
  
  
  CONCLUSIONS
  The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes.
  
  
  CONCLUSIONS
  Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum phosphate, urinary phosphate excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5.
authors.affiliation: Denver Nephrologists PC, Denver, CO. Electronic address: gablock@dnresearch.org.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: Hofstra-North Shore LIJ School of Medicine, Great Neck, NY.
authors.forename: Steven
authors.initials: S
authors.lastname: Fishbane
authors.affiliation: Nephrology Service, IMIBIC, Hospital Universitario, Cordoba, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Denver Nephrologists PC, Denver, CO.
authors.forename: Gerard
authors.initials: G
authors.lastname: Smits
authors.affiliation: Keryx Biopharmaceuticals Inc, New York, NY.
authors.forename: Shay
authors.initials: S
authors.lastname: Shemesh
authors.affiliation: Renal Associates PA, San Antonio, TX.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Pergola
authors.affiliation: Department of Medicine, Institute for Public Health and Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL.
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
mesh_terms: D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood* / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000097:blood*
chemical_list: C000717427:FGF23 protein, human; D005290:Ferric Compounds; D006397:Hematinics; D010710:Phosphates; D005346:Fibroblast Growth Factors; C025314:ferric citrate; D000089703:Fibroblast Growth Factor-23
keywords: Chronic kidney disease (CKD); ferric citrate coordination complex (ferric citrate); fibroblast growth factor 23 (FGF-23); hemoglobin; iron repletion; iron-deficiency anemia; oral iron therapy; phosphate binder; randomized controlled trial; serum phosphate; transferrin saturation (TSAT); urinary phosphate excretion