PMID- 29186198
OWN - NLM
STAT- MEDLINE
DCOM- 20180101
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 11
DP  - 2017
TI  - Safety and efficacy of ferric citrate in patients with nondialysis-dependent 
      chronic kidney disease.
PG  - e0188712
LID - 10.1371/journal.pone.0188712 [doi]
LID - e0188712
AB  - Two randomized, placebo-controlled trials conducted in patients with 
      nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, 
      and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) 
      significantly increased hemoglobin and decreased serum phosphate concentrations. 
      Pooling these trial results could provide a more robust evaluation of the safety 
      and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) 
      and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 
      weeks, respectively. The starting dose in both trials was three 1-g (elemental 
      iron 210 mg) tablets/day with food, up to 12 tablets/day. Doses were titrated in 
      the phase 2 and 3 trials to lower serum phosphate concentrations to a target 
      range (0.97-1.13 mmol/L) and to achieve a >/=10-g/L hemoglobin increase, 
      respectively. Safety was assessed in all patients who received >/=1 dose of FC (n = 
      190) and placebo (n = 188). Treatment-emergent adverse events (AEs) were reported 
      in 143 of 190 (75.3%) FC-treated and 116 of 188 (61.7%) placebo-treated patients; 
      gastrointestinal AEs were the most frequent (94 [49.5%] vs. 52 [27.7%], 
      respectively). Specific events reported in >5% of patients (FC vs. placebo, 
      respectively) included discolored feces (41 [21.6%] vs. 0 [0.0%]), diarrhea (39 
      [20.5%] vs. 23 [12.2%]), constipation (35 [18.4%] vs. 19 [10.1%]), and nausea (18 
      [9.5%] vs. 8 [4.3%]). Twenty FC-treated (10.5%) and 21 placebo-treated patients 
      (11.2%) experienced a serious AE. Two patients (1.1%) died in each group. A 
      pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest 
      serum phosphate decline, with few excursions below the normal range. When used 
      for treatment of patients with NDD-CKD, FC contributes to gastrointestinal AEs at 
      higher rates than placebo, while simultaneously correcting two of the principal 
      metabolic manifestations of CKD (iron deficiency anemia and relative 
      hyperphosphatemia).
FAU - Chertow, Glenn M
AU  - Chertow GM
AUID- ORCID: 0000-0002-7599-0534
AD  - Stanford University School of Medicine, Department of Medicine - Med/Nephrology, 
      Stanford, California, United States of America.
FAU - Block, Geoffrey A
AU  - Block GA
AD  - Denver Nephrology, Denver, Colorado, United States of America.
FAU - Neylan, John F
AU  - Neylan JF
AD  - Keryx Biopharmaceuticals, Inc., Boston, Massachusetts, United States of America.
FAU - Pergola, Pablo E
AU  - Pergola PE
AD  - Renal Associates PA, San Antonio, Texas, United States of America.
FAU - Uhlig, Katrin
AU  - Uhlig K
AD  - Keryx Biopharmaceuticals, Inc., Boston, Massachusetts, United States of America.
FAU - Fishbane, Steven
AU  - Fishbane S
AD  - Hofstra Northwell School of Medicine, Division of Medicine - Kidney Diseases and 
      Hypertension, Great Neck, New York, United States of America.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20171129
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ferric Compounds)
RN  - 0 (Placebos)
RN  - 63G354M39Z (ferric citrate)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia, Iron-Deficiency/complications/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Ferric Compounds/adverse effects/*therapeutic use
MH  - Humans
MH  - Kidney Failure, Chronic/complications/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Placebos
PMC - PMC5706696
COIS- Competing Interests: GMC has served as a consultant to Akebia, Amgen, 
      AstraZeneca, Bristol-Myers Squibb, Gilead, Keryx, and ZS Pharma, has ownership 
      interest in Ardelyx, Durect, Outset, PuraCath Medical, Physiowave, and Thrasos 
      Therapeutics, has received research support from Amgen, Janssen, the National 
      Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, 
      Lung, and Blood Institute, and has received honoraria from the American Society 
      of Nephrology. GAB has served as a consultant for Akebia, Amgen, Ardelyx, 
      AstraZeneca, Celgene, Daiichi Sankyo, Keryx, Relypsa, Sanfit, and ZS Pharma, has 
      ownership interest in Ardelyx and Nephroceuticals, has received research support 
      from Keryx, and has received honoraria from Akebia, Amgen, AstraZeneca, Celgene, 
      Daiichi Sankyo, Keryx, and Sanofi. JFN and KU are employees of Keryx and have 
      ownership interest in Keryx. PEP has served as a consultant for Keryx, Relypsa, 
      Sandoz, Vifor Pharma, and ZS Pharma, and has received honoraria from Keryx, 
      Relypsa, Sandoz, and ZS Pharma. SF has served as a consultant for AstraZeneca, 
      Keryx, Rockwell, and ZS Pharma, has received research funding from Amgen, 
      AstraZeneca, Janssen, and ZS Pharma, and has received honoraria from AstraZeneca, 
      Keryx, Rockwell, and ZS Pharma. This does not alter our adherence to PLOS ONE 
      policies on sharing data and materials.
EDAT- 2017/12/01 06:00
MHDA- 2018/01/02 06:00
PMCR- 2017/11/29
CRDT- 2017/11/30 06:00
PHST- 2017/06/09 00:00 [received]
PHST- 2017/11/08 00:00 [accepted]
PHST- 2017/11/30 06:00 [entrez]
PHST- 2017/12/01 06:00 [pubmed]
PHST- 2018/01/02 06:00 [medline]
PHST- 2017/11/29 00:00 [pmc-release]
AID - PONE-D-17-22064 [pii]
AID - 10.1371/journal.pone.0188712 [doi]
PST - epublish
SO  - PLoS One. 2017 Nov 29;12(11):e0188712. doi: 10.1371/journal.pone.0188712. 
      eCollection 2017.