International Journal of Molecular Sciences (Sep 2023)
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
Affiliations
- Naohisa Tomosugi
- Division of Systems Bioscience for Drug Discovery, Project Research Center, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
- Yoshitaka Koshino
- Mizuho Hospital, Tsubata 929-0346, Ishikawa, Japan
- Chie Ogawa
- Maeda Institute of Renal Research Musashikosugi, Kawasaki 211-0063, Kanagawa, Japan
- Kunimi Maeda
- Maeda Institute of Renal Research Shakujii, Nerima 177-0041, Tokyo, Japan
- Noriaki Shimada
- Tachibana Clinic, Sumida 131-0043, Tokyo, Japan
- Kimio Tomita
- The Chronic Kidney Disease Research Center, Tomei Atsugi General Hospital, Atsugi 243-8571, Kanagawa, Japan
- Shoichiro Daimon
- Department of Nephrology, Daimon Clinic for Internal Medicine, Nonoichi 921-8802, Ishikawa, Japan
- Tsutomu Shikano
- Kyoto Okamoto Memorial Hospital, Kuze 613-0034, Kyoto, Japan
- Kazuyuki Ryu
- Kyoto Okamoto Memorial Hospital, Kuze 613-0034, Kyoto, Japan
- Toru Takatani
- Nephrology Division, Tojinkai Hospital, Fushimi 612-8026, Kyoto, Japan
- Kazuya Sakamoto
- Department of Urology, Tomakomai Nisshou Hospital, Tomakomai 053-0803, Hokkaido, Japan
- Satonori Ueyama
- Jinaikai Ueyama Hospital, Kagoshima 890-0073, Kagoshima, Japan
- Daisuke Nagasaku
- Yujin-Yamazaki Hospital, Hikone 522-0044, Shiga, Japan
- Masato Nakamura
- Susono Daiichi Clinic, Susono 410-1112, Shizuoka, Japan
- Shibun Ra
- Noheji Clinic, Noheji 039-3152, Aomori, Japan
- Masataka Nishimura
- Shimosaka Clinic, Nagahama 526-0044, Shiga, Japan
- Chieko Takagi
- Ohgo Clinic, Maebashi 371-0232, Gunma, Japan
- Yoji Ishii
- Nozatomon Clinic, Himeji 670-0011, Hyogo, Japan
- Noritoshi Kudo
- Kowa Clinic, Goshogawara 037-0066, Aomori, Japan
- Shinsuke Takechi
- Takechi Clinic, Iyo 791-3141, Ehime, Japan
- Takashi Ishizu
- Department of Nephrology, Tsukuba Central Hospital, Ushiku 300-1211, Ibaraki, Japan
- Takamoto Yanagawa
- Department of Nephrology, Tsukuba Central Hospital, Ushiku 300-1211, Ibaraki, Japan
- Masamichi Fukuda
- Iwakuni Medical Center, Iwakuni 740-0021, Yamaguchi, Japan
- Yutaka Nitta
- The Department of Nephrology, Saiseikai Shimonoseki General Hospital, Shimonoseki 759-6603, Yamaguchi, Japan
- Takayuki Yamaoka
- The Department of Nephrology, Saiseikai Shimonoseki General Hospital, Shimonoseki 759-6603, Yamaguchi, Japan
- Taku Saito
- Saito Memorial Hospital, Kawaguchi 332-0034, Saitama, Japan
- Suzuko Imayoshi
- Saito Memorial Hospital, Kawaguchi 332-0034, Saitama, Japan
- Momoyo Omata
- Department of Internal Medicine, Hachioji Azumacho Clinic, Hachioji-shi 192-0082, Tokyo, Japan
- Joji Oshima
- Kubojima Clinic, Kumagaya 360-0831, Saitama, Japan
- Akira Onozaki
- Tokatsu-Clinic Hospital, Matsudo 271-0067, Chiba, Japan
- Hiroaki Ichihashi
- Tokatsu Clinic Yabashira, Matsudo 270-2253, Chiba, Japan
- Yasuhisa Matsushima
- Tokatsu Clinic Kashiwa, Kashiwa 277-0005, Chiba, Japan
- Hisahito Takae
- Tokatsu Clinic Matsudo, Matsudo 271-0077, Chiba, Japan
- Ryoichi Nakazawa
- Tokatsu Clinic Mirai, Matsudo 271-0091, Chiba, Japan
- Koichi Ikeda
- Tokatsu Clinic Koiwa, Edogawa 133-0056, Tokyo, Japan
- Masato Tsuboi
- Kaikoukai Anjo Kyoritsu Clinic, Anjo 446-0065, Aichi, Japan
- Keiko Konishi
- Seiwa Hospital, Toyama 931-8431, Toyama, Japan
- Shouzaburo Kato
- Nishi Interchange Clinic for Internal Medicine and Dialysis, Kanazawa 921-8001, Ishikawa, Japan
- Maki Ooura
- Maro Clinic, Tanabe 646-0004, Wakayama, Japan
- Masaki Koyama
- Nishijin Hospital, Kyoto 602-8319, Kyoto, Japan
- Tsukasa Naganuma
- Department of Nephrology, Yamanashi Prefectural Central Hospital, Kofu 400-0027, Yamanashi, Japan
- Makoto Ogi
- Department of Internal Medicine, Yuurinkouseikai Fuji Hospital, Gotemba 412-0043, Shizuoka, Japan
- Shigeyuki Katayama
- Katayama Clinic, Iwakuni 741-0072, Yamaguchi, Japan
- Toshiaki Okumura
- Mizue Yuai Clinic, Edogawa 133-0065, Tokyo, Japan
- Shigemi Kameda
- Joetsu General Hospital, Joetsu 943-8507, Niigata, Japan
- Sayuri Shirai
- Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University Yokohama Seibu Hospital, Yokohama 241-0811, Kanagawa, Japan
- DOI
- https://doi.org/10.3390/ijms241813779
- Journal volume & issue
-
Vol. 24,
no. 18
p. 13779
Abstract
Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was 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 with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body’s iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (−0.459, −0.643 to −0.276, p = 0.000; −0.648, −1.099 to −0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (−1.392, −1.749 to −1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). 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.
Keywords
