TY - JOUR
T1 - 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
AU - Block, Geoffrey A.
AU - Fishbane, Steven
AU - Rodriguez, Mariano
AU - Smits, Gerard
AU - Shemesh, Shay
AU - Pergola, Pablo E.
AU - Wolf, Myles
AU - Chertow, Glenn M.
N1 - Funding Information:
Disclosures: Drs Block and Pergola: consultant, research grant for Keryx Biopharmaceuticals Inc; Drs Chertow, Fishbane, Smits, and Wolf: consultant for Keryx Biopharmaceuticals, Inc; and Mr Shemesh: employee of and owns stock in Keryx Biopharmaceuticals Inc.
Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Background: Iron deficiency anemia and serum phosphate levels > 4.0 mg/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. Study Design: Double-blind, placebo-controlled, randomized trial. Setting & Participants: 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m2, 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 6.0 mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. Intervention: Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. Outcomes & Measurements: 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. Limitations: 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.
AB - Background: Iron deficiency anemia and serum phosphate levels > 4.0 mg/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. Study Design: Double-blind, placebo-controlled, randomized trial. Setting & Participants: 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m2, 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 6.0 mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. Intervention: Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. Outcomes & Measurements: 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. Limitations: 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.
KW - Chronic kidney disease (CKD)
KW - ferric citrate coordination complex (ferric citrate)
KW - fibroblast growth factor 23 (FGF-23)
KW - hemoglobin
KW - iron repletion
KW - iron-deficiency anemia
KW - oral iron therapy
KW - phosphate binder
KW - randomized controlled trial
KW - serum phosphate
KW - transferrin saturation (TSAT)
KW - urinary phosphate excretion
UR - http://www.scopus.com/inward/record.url?scp=84926493841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926493841&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2014.10.014
DO - 10.1053/j.ajkd.2014.10.014
M3 - Article
C2 - 25468387
AN - SCOPUS:84926493841
SN - 0272-6386
VL - 65
SP - 728
EP - 736
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 5
ER -