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 > 4.0 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.