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中华肾病研究电子杂志 ›› 2017, Vol. 06 ›› Issue (02) : 83 -87. doi: 10.3877/cma.j.issn.2095-3216.2017.02.008

所属专题: 文献

综述

慢性肾脏病铁稳态的研究及治疗进展
刘洋1, 赖学莉2, 郭志勇2,()   
  1. 1. 200433 第二军医大学学员旅学院1队
    2. 200433 第二军医大学附属长海医院肾内科
  • 收稿日期:2017-02-12 出版日期:2017-04-28
  • 通信作者: 郭志勇
  • 基金资助:
    上海市卫计委科研基金(20134Y035); 中国博士后基金面上项目(2014M562591); 百特中国RRG基金(CHN-RENAL-IIS-2010-068)

Research and treatment progress in iron homeostasis of chronic kidney disease

Yang Liu1, Xueli Lai2, Zhiyong Guo2,()   

  1. 1. Team 1 of Second Military Medical University School of Cadet Brigade
    2. Department of Nephrology, Second Military Medical University Affiliated Changhai Hospital; Shanghai 200433, China
  • Received:2017-02-12 Published:2017-04-28
  • Corresponding author: Zhiyong Guo
  • About author:
    Corresponding author: Guo Zhiyong, Email:
引用本文:

刘洋, 赖学莉, 郭志勇. 慢性肾脏病铁稳态的研究及治疗进展[J]. 中华肾病研究电子杂志, 2017, 06(02): 83-87.

Yang Liu, Xueli Lai, Zhiyong Guo. Research and treatment progress in iron homeostasis of chronic kidney disease[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2017, 06(02): 83-87.

铁是几乎所有生物存活所必须的微量元素。铁在氧气运输中起到重要作用,铁缺乏会导致贫血,影响氧的供给。在慢性肾脏病中会出现铁代谢的紊乱,使调节铁代谢的细胞因子水平发生变化。慢性肾脏病导致的铁代谢紊乱主要为铁元素缺乏,而补充铁剂的治疗,会导致一系列的氧化应激反应,此为目前临床治疗的难点。认识铁元素在慢性肾脏病中的调节机制是实现铁剂精准治疗的重要前提,本文将从慢性肾脏病中的铁稳态失衡入手,从精准治疗的角度进行综述,以期深入分析铁稳态与慢性肾脏病间的联系,为优化铁剂补充方式提供参考,从而达到减少不良反应的目的。

Iron is the essential trace element for almost all organisms. Due to the function of iron in oxygen transportation, lack of iron may lead to anemia and affect oxygen supply. Iron metabolism disorders may appear in chronic kidney disease (CKD), and make change the levels of cytokines responsible for regulation of iron metabolism. Because various causes can lead to iron deficiency in patients with kidney disease, iron supplement therapy is usually given. However, iron supplement therapy may contribute to a series of oxidative stress responses, which is the difficult point in current clinical treatment. Understanding the iron regulation mechanism in CKD is an important prerequisite for the precise treatment of iron supplement. The authors started from the imbalance of iron homeostasis in CKD, and focused on precise treatment of iron supplement, hoping to further analyze the relation of iron homeostasis to CKD, in order to provide a reference for optimizing the iron supplement mode, and achieve the purpose of reducing adverse reactions.

[1]
Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation[J]. Blood, 2003,102(3): 783-788.
[2]
Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization[J]. Science, 2004,306(5704): 2090-2093.
[3]
Vaziri ND, Kalantar-Zadeh K, Wish JB. New Options for Iron Supplementation in Maintenance Hemodialysis Patients[J]. Am J Kidney Dis, 2016,67(3): 367-375.
[4]
Chung J, Wessling-Resnick M. Molecular mechanisms and regulation of iron transport[J]. Crit Rev Clin Lab Sci, 2003,40(2): 151-182.
[5]
Latunde-Dada GO, Van der Westhuizen J, Vulpe CD, et al. Molecular and functional roles of duodenal cytochrome B (Dcytb) in iron metabolism[J]. Blood Cells Mol Dis, 2002,29(3): 356-360.
[6]
Andrews NC. The iron transporter DMT1[J]. Int J Biochem Cell Biol, 1999,31(10): 991-994.
[7]
Gunshin H, Starr CN, Direnzo C, et al. Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice[J]. Blood, 2005,106(8): 2879-2883.
[8]
Crichton RR. Proteins of iron storage and transport[J]. Adv Protein Chem, 1990,40: 281-363.
[9]
Chung B, Chaston T, Marks J, et al. Hepcidin decreases iron transporter expression in vivo in mouse duodenum and spleen and in vitro in THP-1 macrophages and intestinal Caco-2 cells[J]. J Nutr, 2009,139(8): 1457-1462.
[10]
Hentze MW, Muckenthaler MU, Andrews NC. Balancing acts: molecular control of mammalian iron metabolism[J]. Cell, 2004,117(3): 285-297.
[11]
Park CH, Valore EV, Waring AJ, et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver[J]. J Biol Chem, 2001,276(11): 7806-7810.
[12]
Donovan A, Lima CA, Pinkus JL, et al. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis[J]. Cell Metab, 2005,1(3): 191-200.
[13]
Rivera S, Nemeth E, Gabayan V, et al. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs[J]. Blood, 2005,106(6): 2196-2199.
[14]
Roetto A, Papanikolaou G, Politou M, et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis[J]. Nat Genet, 2003,33(1): 21-22.
[15]
Meynard D, Kautz L, Darnaud V, et al. Lack of the bone morphogenetic protein BMP6 induces massive iron overload[J]. Nat Genet, 2009,41(4): 478-481.
[16]
Steinbicker AU, Bartnikas TB, Lohmeyer LK, et al. Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice[J]. Blood, 2011,118(15): 4224-4230.
[17]
Wang RH, Li C, Xu X, et al. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression[J]. Cell Metab, 2005,2(6): 399-409.
[18]
Zhang AS, Gao J, Koeberl DD, et al. The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein-6 and hepcidin expression in vivo[J]. J Biol Chem, 2010,285(22): 16416-16423.
[19]
Ramos E, Kautz L, Rodriguez R, et al. Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice[J]. Hepatology, 2011,53(4): 1333-1341.
[20]
Johnson MB, Chen J, Murchison N, et al. Transferrin receptor 2: evidence for ligand-induced stabilization and redirection to a recycling pathway[J]. Mol Biol Cell, 2007,18(3): 743-754.
[21]
Feng Q, Migas MC, Waheed A, et al. Ferritin upregulates hepatic expression of bone morphogenetic protein 6 and hepcidin in mice[J]. Am J Physiol Gastrointest Liver Physiol, 2012,302(12): G1397-G1404.
[22]
Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin[J]. J Clin Invest, 2004,113(9): 1271-1276.
[23]
Besson-Fournier C, Latour C, Kautz L, et al. Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling[J]. Blood, 2012,120(2): 431-439.
[24]
Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease[J]. N Engl J Med, 2009,361(21): 2019-2032.
[25]
Cooke KS, Hinkle B, Salimi-Moosavi H, et al. A fully human anti-hepcidin antibody modulates iron metabolism in both mice and nonhuman primates[J]. Blood, 2013,122(17): 3054-3061.
[26]
Sun CC, Vaja V, Babitt JL, et al. Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation[J]. Am J Hematol, 2012,87(4): 392-400.
[27]
Panwar B, Gutierrez OM. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease[J]. Semin Nephrol, 2016,36(4): 252-261.
[28]
Babitt JL, Lin HY. Mechanisms of anemia in CKD[J]. J Am Soc Nephrol, 2012,23(10): 1631-1634.
[29]
Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease[J]. Kidney Int, 2007,71(1): 31-38.
[30]
Perlstein TS, Pande R, Berliner N, et al. Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: association with anemia of inflammation[J]. Blood, 2011,117(10): 2800-2806.
[31]
Bacchetta J, Zaritsky JJ, Sea JL, et al. Suppression of iron-regulatory hepcidin by vitamin D[J]. J Am Soc Nephrol, 2014,25(3): 564-572.
[32]
Liu S, Quarles LD. How fibroblast growth factor 23 works[J]. J Am Soc Nephrol, 2007,18(6): 1637-1647.
[33]
Wolf M, White KE. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease[J]. Curr Opin Nephrol Hypertens, 2014,23(4): 411-419.
[34]
Bacchetta J, Zaritsky JJ, Sea JL, et al. Suppression of iron-regulatory hepcidin by vitamin D[J]. J Am Soc Nephrol, 2014,25(3): 564-572.
[35]
Zughaier SM, Alvarez JA, Sloan JH, et al. The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes[J]. J Clin Transl Endocrinol, 2014,1(1): 19-25.
[36]
Clinkenbeard EL, Farrow EG, Summers LJ, et al. Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice[J]. J Bone Miner Res, 2014,29(2): 361-369.
[37]
Smith ER, Cai MM, McMahon LP, et al. Biological variability of plasma intact and C-terminal FGF23 measurements[J]. J Clin Endocrinol Metab, 2012,97(9): 3357-3365.
[38]
Torti FM, Torti SV. Regulation of ferritin genes and protein[J]. Blood, 2002,99(10): 3505-3516.
[39]
Ford BA, Coyne DW, Eby CS, et al. Variability of ferritin measurements in chronic kidney disease; implications for iron management[J]. Kidney Int, 2009,75(1): 104-110.
[40]
Spada PL, Rossi C, Alimonti A, et al. Ferritin iron content in haemodialysis patients: comparison with septic and hemochromatosis patients[J]. Clin Biochem, 2008,41(12): 997-1001.
[41]
R′Zik S, Beguin Y. Serum soluble transferrin receptor concentration is an accurate estimate of the mass of tissue receptors[J]. Exp Hematol, 2001,29(6): 677-685.
[42]
Singh AK, Coyne DW, Shapiro W, et al. Predictors of the response to treatment in anemic hemodialysis patients with high serum ferritin and low transferrin saturation[J]. Kidney Int, 2007,71(11): 1163-1171.
[43]
Piga A, Longo F, Duca L, et al. High nontransferrin bound iron levels and heart disease in thalassemia major[J]. Am J Hematol, 2009,84(1): 29-33.
[44]
Prus E, Fibach E. The labile iron pool in human erythroid cells[J]. Br J Haematol, 2008,142(2): 301-307.
[45]
Pootrakul P, Breuer W, Sametband M, et al. Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator[J]. Blood, 2004,104(5): 1504-1510.
[46]
Scheiber-Mojdehkar B, Lutzky B, Schaufler R, et al. Non-transferrin-bound iron in the serum of hemodialysis patients who receive ferric saccharate: no correlation to peroxide generation[J]. J Am Soc Nephrol, 2004,15(6): 1648-1655.
[47]
Prus E, Fibach E. Flow cytometry measurement of the labile iron pool in human hematopoietic cells[J]. Cytometry A, 2008,73(1): 22-27.
[48]
Wu Q, Lai X, Zhao H, et al. A metabolomics approach for predicting the response to intravenous iron therapy in peritoneal dialysis patients with anemia[J]. RSC Adv, 2017,7: 1915-1922.
[49]
Umanath K, Jalal DI, Greco BA, et al. Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD[J]. J Am Soc Nephrol, 2015,26(10): 2578-2587.
[50]
Gupta A, Amin NB, Besarab A, et al. Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis[J]. Kidney Int, 1999,55(5): 1891-1898.
[51]
Fishbane SN, Singh AK, Cournoyer SH, et al. Ferric pyrophosphate citrate (Triferic) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients[J]. Nephrol Dial Transplant, 2015,30(12): 2019-2026.
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