Project Description

Intestinal uptake of iron delivered as ferric citrate | Iron Metabolism

Kidney Int. 2022 Apr;101(4):668-670. doi: 10.1016/j.kint.2021.12.032.

The ins and outs of ferric citrate.

Commentary on the molecular mechanisms underlying the intestinal uptake of iron delivered as ferric citrate.

Haase VH

Ferric citrate is used clinically for the treatment of hyperphosphatemia in patients with chronic kidney disease and is approved as an oral iron replacement product for patients with iron-deficiency anemia. In this issue of Kidney International, Hanudel and colleagues take advantage of genetic models with and without chronic kidney injury to demonstrate that the enteric absorption of iron delivered by ferric citrate is dependent on ferroportin expression and does not involve paracellular iron transport.

In addition to erythropoietin (EPO) deficiency, absolute iron deficiency and functional iron deficiency have been identified as key contributors to anemia associated with chronic kidney disease (CKD). Ferric citrate, an iron- containing phosphate binder, is effective in treating hyperphosphatemia and has been approved in the US for the treatment of iron-deficiency anemia (IDA) in patients with CKD not on dialysis, and more recently in Japan for patients with IDA. In randomized clinical trials, ferric citrate raised transferrin saturation, serum ferritin, and hemoglobin (Hb) levels, compared with placebo in non-dialysis-dependent CKD patients, and decreased i.v. iron and erythropoiesis-stimulating agent use in patients with end-stage kidney disease.

Recent studies in animals showed that more iron was taken up in ferric citrate-treated rats under conditions of IDA, iron overload, and inflammation, compared with those treated with sucroferric oxyhydroxide, another iron-based phosphate binder. These findings raised the possibility that the presence of citrate in the intestinal lumen may have enhanced iron uptake through paracellular absorption, as citrate can disrupt tight junction integrity between enterocytes, via calcium chelation, and thus promote, for example, the uptake of aluminum in patients with CKD.

The ins and outs of ferric citrate

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link to paper by Hanudel and colleagues in Kidney International, April 2022