title: Ferric citrate hydrate for the treatment of hyperphosphatemia in nondialysis-dependent CKD.
abstract: OBJECTIVE
  Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD.
  
  
  METHODS
  A phase 3, multicenter, randomized, double blind, placebo-controlled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD. Starting in April of 2011, 90 CKD patients (eGFR=9.21±5.72 ml/min per 1.73 m(2)) with a serum phosphate≥5.0 mg/dl were randomized 2:1 to ferric citrate hydrate or placebo for 12 weeks. The primary end point was change in serum phosphate from baseline to the end of treatment. Secondary end points included the percentage of patients achieving target serum phosphate levels (2.5-4.5 mg/dl) and change in fibroblast growth factor-23 at the end of treatment.
  
  
  RESULTS
  The mean change in serum phosphate was -1.29 mg/dl (95% confidence interval, -1.63 to -0.96 mg/dl) in the ferric citrate hydrate group and 0.06 mg/dl (95% confidence interval, -0.20 to 0.31 mg/dl) in the placebo group (P<0.001 for difference between groups). The percentage of patients achieving target serum phosphate levels was 64.9% in the ferric citrate hydrate group and 6.9% in the placebo group (P<0.001). Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo (change from baseline [median], -142.0 versus 67.0 pg/ml; P<0.001). Ferric citrate hydrate significantly increased serum iron, ferritin, and transferrin saturation compared with placebo (P=0.001 or P<0.001). Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo. Overall, adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo, with gastrointestinal disorders occurring in 30.0% of ferric citrate hydrate patients and 26.7% of patients receiving placebo.
  
  
  CONCLUSIONS
  In patients with nondialysis-dependent CKD, 12-week treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters.
authors.affiliation: Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan;, †Japanese Red Cross, Fukuoka Hospital, Fukuoka, Japan;, ‡Department of Blood Purification, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan;, §Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan;, ‖Department of Nephrology, Hypertension, Diabetology, Endocrinology, and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan;, ¶Department of Hematology, Nephrology and Rheumatology, Akita University, Akita, Japan;, *Kitasato University East Hospital Clinical Trial Center, Sagamihara, Japan, ††Denver Nephrologists, PC, Denver, Colorado.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Hirakata
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiba
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sawada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005290:Ferric Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D005293:Ferritins / Q000097:blood; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D007501:Iron / Q000097:blood; D007564:Japan; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000175:diagnosis; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002614:Chelating Agents; D005290:Ferric Compounds; D010710:Phosphates; D014168:Transferrin; D005346:Fibroblast Growth Factors; C025314:ferric citrate; D000089703:Fibroblast Growth Factor-23; D005293:Ferritins; D007501:Iron