title: The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial.
abstract: BACKGROUND
  Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels.
  
  
  METHODS
  52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment.
  
  
  METHODS
  Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders.
  
  
  METHODS
  2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate).
  
  
  RESULTS
  Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year.
  
  
  METHODS
  Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate.
  
  
  RESULTS
  There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25 mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95 mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1 pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control.
  
  
  CONCLUSIONS
  Open-label study, few peritoneal dialysis patients.
  
  
  CONCLUSIONS
  Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: peter.vanburen@utsouthwestern.edu.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Van Buren
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Lewis
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Jamie P
authors.initials: JP
authors.lastname: Dwyer
authors.affiliation: University of Utah Medical Center, Salt Lake City, UT.
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.affiliation: Duke University Medical Center, Durham, NC.
authors.forename: John
authors.initials: J
authors.lastname: Middleton
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sika
authors.affiliation: Henry Ford Medical Center, Detroit, MI.
authors.forename: Kausik
authors.initials: K
authors.lastname: Umanath
authors.affiliation: University of Utah Medical Center, Salt Lake City, UT.
authors.forename: Josephine D
authors.initials: JD
authors.lastname: Abraham
authors.affiliation: Nephrology Specialists PC, Michigan City, IN.
authors.forename: Shahabul S
authors.initials: SS
authors.lastname: Arfeen
authors.affiliation: Wake Forest University Medical Center, Winston-Salem, NC.
authors.forename: Isai G
authors.initials: IG
authors.lastname: Bowline
authors.affiliation: Ichilov Medical Center, Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Chernin
authors.affiliation: Kidney Associates PLLC, Houston, TX.
authors.forename: Stephen Z
authors.initials: SZ
authors.lastname: Fadem
authors.affiliation: University of Pennsylvania Medical Center, Philadelphia, PA.
authors.forename: Simin
authors.initials: S
authors.lastname: Goral
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Mark
authors.initials: M
authors.lastname: Koury
authors.affiliation: Rush University Medical Center, Chicago, IL.
authors.forename: Marvin V
authors.initials: MV
authors.lastname: Sinsakul
authors.affiliation: Tufts Medical Center, Boston, MA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weiner
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000368:Aged; D002118:Calcium / Q000097:blood; D017610:Calcium Compounds / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use*; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D006801:Humans; D054559:Hyperphosphatemia / Q000188:drug therapy; D018836:Inflammation Mediators / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000378:metabolism*; D011073:Polyamines / Q000627:therapeutic use; D006435:Renal Dialysis; D000069603:Sevelamer
chemical_list: D000085:Acetates; D017610:Calcium Compounds; D002614:Chelating Agents; D005290:Ferric Compounds; D018836:Inflammation Mediators; D010710:Phosphates; D011073:Polyamines; C025314:ferric citrate; D000069603:Sevelamer; D002118:Calcium; C120662:calcium acetate
keywords: Hemodialysis; adverse events; calcium acetate; end-stage renal disease (ESRD); ferric citrate; hyperphosphatemia; mineral bone disease; phosphate binder; protein-energy wasting (PEW)/inflammation; safety; sevelamer carbonate