Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial

Naohisa Tomosugi; Yoshitaka Koshino; Chie Ogawa; Kunimi Maeda; Noriaki Shimada; Kimio Tomita; Shoichiro Daimon; Tsutomu Shikano; Kazuyuki Ryu; Toru Takatani; Kazuya Sakamoto; Satonori Ueyama; Daisuke Nagasaku; Masato Nakamura; Shibun Ra; Masataka Nishimura; Chieko Takagi; Yoji Ishii; Noritoshi Kudo; Shinsuke Takechi; Takashi Ishizu; Takamoto Yanagawa; Masamichi Fukuda; Yutaka Nitta; Takayuki Yamaoka; Taku Saito; Suzuko Imayoshi; Momoyo Omata; Joji Oshima; Akira Onozaki; Hiroaki Ichihashi; Yasuhisa Matsushima; Hisahito Takae; Ryoichi Nakazawa; Koichi Ikeda; Masato Tsuboi; Keiko Konishi; Shouzaburo Kato; Maki Ooura; Masaki Koyama; Tsukasa Naganuma; Makoto Ogi; Shigeyuki Katayama; Toshiaki Okumura; Shigemi Kameda; Sayuri Shirai

doi:10.20944/preprints202308.1352.v1

A peer-reviewed article of this Preprint also exists.

Tomosugi, N.; Koshino, Y.; Ogawa, C.; Maeda, K.; Shimada, N.; Tomita, K.; Daimon, S.; Shikano, T.; Ryu, K.; Takatani, T.; Sakamoto, K.; Ueyama, S.; Nagasaku, D.; Nakamura, M.; Ra, S.; Nishimura, M.; Takagi, C.; Ishii, Y.; Kudo, N.; Takechi, S.; Ishizu, T.; Yanagawa, T.; Fukuda, M.; Nitta, Y.; Yamaoka, T.; Saito, T.; Imayoshi, S.; Omata, M.; Oshima, J.; Onozaki, A.; Ichihashi, H.; Matsushima, Y.; Takae, H.; Nakazawa, R.; Ikeda, K.; Tsuboi, M.; Konishi, K.; Kato, S.; Ooura, M.; Koyama, M.; Naganuma, T.; Ogi, M.; Katayama, S.; Okumura, T.; Kameda, S.; Shirai, S. Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial. Int. J. Mol. Sci. 2023, 24, 13779. Tomosugi, N.; Koshino, Y.; Ogawa, C.; Maeda, K.; Shimada, N.; Tomita, K.; Daimon, S.; Shikano, T.; Ryu, K.; Takatani, T.; Sakamoto, K.; Ueyama, S.; Nagasaku, D.; Nakamura, M.; Ra, S.; Nishimura, M.; Takagi, C.; Ishii, Y.; Kudo, N.; Takechi, S.; Ishizu, T.; Yanagawa, T.; Fukuda, M.; Nitta, Y.; Yamaoka, T.; Saito, T.; Imayoshi, S.; Omata, M.; Oshima, J.; Onozaki, A.; Ichihashi, H.; Matsushima, Y.; Takae, H.; Nakazawa, R.; Ikeda, K.; Tsuboi, M.; Konishi, K.; Kato, S.; Ooura, M.; Koyama, M.; Naganuma, T.; Ogi, M.; Katayama, S.; Okumura, T.; Kameda, S.; Shirai, S. Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial. Int. J. Mol. Sci. 2023, 24, 13779.

Abstract

Oral ferric citrate hydrate (FCH) is effective for iron deficiency in hemodialysis patients.; however, it remains unclear how iron balance in the body affects iron absorption from the intestinal tract. This prospective, observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406), conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables on ΔFe2h and the secondary outcome was the description of the predictors of body iron balance. Generalized estimating equations (GEE) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and MCH decreased (-0.155, -0.242 to -0.068, p = 0.001; -2.574, -4.421 to -0.726, p = 0.006, respectively) in GEE. Hepcidin-25 increased when erythropoiesis-stimulating agent (ESA) decreased (-0.002, -0.002 to -0.001, p=0.000). FTN increased when RBC and ESA decreased (-0.466, -0.605 to -0.327, p=0.000; -0.002, -0.004 to -0.000, p=0.05, respectively. Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC-iron to FTN-iron, inhibiting iron absorption even with continued FCH intake.

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Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial

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