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.

Phosphate Binder, Ferric Citrate, Attenuates Anemia, Renal Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in 5/6 Nephrectomized CKD Rats

“…Uptake of citrate through short chain fatty acid transporters by colonic epithelial cells can be, in turn, followed by uptake of iron to maintain electrical neutrality. This phenomenon may account for atypical iron absorption in the reported FC-treated CKD patients (Block et al, 2015;Lewis et al, 2015;Tanaka et al, 2016;Fishbane et al, 2017) and CKD rats shown in our study by bypassing the normal route of iron absorption.…”

“…Due to impaired iron absorption, most ESRD patients are routinely treated with intravenous iron products. However, oral administration of FC has been reported to expand iron stores and lower the need for parenteral iron products in the CKD and ESRD populations (Block et al, 2015;Lewis et al, 2015;Tanaka et al, 2016;Fishbane et al, 2017). To our knowledge the This article has not been copyedited and formatted.…”

“…Use of the ferric citrate complex, which is an iron-containing phosphate binder, increases body iron stores, raises hemoglobin level, and reduces the need for ESA and IV iron in ESRD and CKD patients (Block et al, 2015;Lewis et al, 2015). A recent phase 3 clinical trial demonstrated the safety and efficacy of ferric citrate for treatment of iron deficiency anemia in dialysis-independent CKD patients (Fishbane et al, 2017).…”

Hemoglobin response to ferric citrate in patients with nondialysis‐dependent chronic kidney disease and iron deficiency anemia

“…In a randomized placebo‐controlled trial of ferric citrate in 234 patients with NDD‐CKD and iron deficiency anemia,2 ferric citrate‐treated patients were significantly more likely to achieve a ≥1.0 g/dL increase in hemoglobin (52.1% vs. 19.1% with placebo; P  < .001) during the 16‐week randomized phase; the least‐squares mean (LSM) relative change in hemoglobin was 0.84 g/dL (95% confidence interval [CI], 0.58‐1.10) 2…”

“…Full clinical trial details are described elsewhere 2. Here, multivariable linear regression analysis was used to identify variables associated with change in hemoglobin from baseline to week 16.…”