Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency Anemia

Abstract

Iron deficiency anemia is common and consequential in nondialysis-dependent CKD (NDD-CKD). Efficacy and tolerability of conventional oral iron supplements are mixed; intravenous iron administration associates with finite but important risks. We conducted a randomized double-blind clinical trial in adults with NDD-CKD and iron deficiency anemia to compare the safety and efficacy of oral ferric citrate (n=117) and placebo (n=115). The primary end point was the proportion of patients who achieved a ≥1.0 g/dl increase in hemoglobin at any time during a 16-week randomized period. Patients who completed the 16-week period could also participate in an 8-week open-label extension period. Significantly more patients randomized to ferric citrate achieved the primary end point (61 [52.1%] versus 22 [19.1%] with placebo; P<0.001). All secondary end points reached statistical significance in the ferric citrate group, including the mean relative change in hemoglobin (0.84 g/dl; 95% confidence interval, 0.58 to 1.10 g/dl; P<0.001) and the proportion of patients who achieved a sustained increase in hemoglobin (≥0.75 g/dl over any 4-week period during the randomized trial; 57 [48.7%] versus 17 [14.8%] with placebo; P<0.001). Rates of serious adverse events were similar in the ferric citrate (12.0%) and placebo groups (11.2%). Gastrointestinal disorders were the most common adverse events, with diarrhea reported in 24 (20.5%) and 19 (16.4%) and constipation in 22 (18.8%) and 15 (12.9%) patients treated with ferric citrate and placebo, respectively. Overall, in patients with NDD-CKD, we found oral ferric citrate to be a safe and efficacious treatment for iron deficiency anemia.

Keywords: anemia; blood transfusion; clinical trial; hemoglobin; iron deficiency; renal dialysis.

Figure 1.

Consolidated Standards of Reporting Trials diagram.

Figure 2.

Ferric citrate improves hemoglobin response. (A) Mean hemoglobin concentration by study week (P<0.001). (B) Proportion of patients with ≥1 g/dl increase in hemoglobin at any time during the randomized trial period (primary efficacy end point) (P<0.001). (C) Time to first hemoglobin increase ≥1 g/dl (P<0.001). (D) Proportion of patients with sustained increase in hemoglobin during the randomized period (P<0.001). (E) Forest plot of differences in proportion of patients achieving primary efficacy end point by prespecified subgroups (all P>0.10). P values refer to comparisons between treatment groups.

Figure 3.

Ferric citrate increases transferrin saturation and serum ferritin. (A) Mean transferrin saturation by study week (P<0.001). (B) Mean serum ferritin by study week (P<0.001). P values refer to comparisons between treatment groups.

Figure 4.

Ferric citrate reduced serum phosphate. Mean serum phosphate by study week (P<0.001). P value refers to comparisons between treatment groups.