肾性贫血和铁代谢的研究进展
Research Progress of Renal Anemia and Iron Metabolism
DOI: 10.12677/ACM.2022.121071, PDF,  被引量    国家自然科学基金支持
作者: 刘 静:西安医学院,陕西 西安;何 鹏, 王汉民, 何丽洁, 张 鹏*:空军军医大学西京医院肾内科,陕西 西安
关键词: 慢性肾脏病肾性贫血铁代谢铁调素Chronic Kidney Disease Renal Anemia Iron Metabolism Hepcidin
摘要: 肾性贫血是慢性肾功能不全发展到终末期肾脏病常见的并发症之一,会导致患者机体功能受损和生活质量下降,同时增加慢性肾脏病(chronic kidney disease, CKD)患者的死亡风险。铁代谢平衡对维持机体正常生理功能至关重要,铁稳态失衡是导致CKD患者绝对或功能性缺铁性贫血的一个重要原因。本文将就近些年来肾性贫血的诊断与治疗目标、铁代谢、铁调素和肾性贫血药物治疗的研究进展作一综述。
Abstract: Renal anemia is one of the common complications of chronic renal insufficiency to end-stage renal disease, which will lead to impaired body function and decreased quality of life, and increase the risk of death in patients with chronic kidney disease. Iron metabolism balance is crucial to maintain normal physiological functions of the body, and iron homeostasis imbalance is an important cause of absolute or functional iron deficiency anemia in patients with CKD. This article will review the diagnosis and treatment of renal anemia, iron metabolism, hepcidin and drug therapy of renal anemia in recent years.
文章引用:刘静, 何鹏, 王汉民, 何丽洁, 张鹏. 肾性贫血和铁代谢的研究进展[J]. 临床医学进展, 2022, 12(1): 483-489. https://doi.org/10.12677/ACM.2022.121071

参考文献

[1] Jha, V., Garcia-Garcia, G., Iseki, K., et al. (2013) Chronic Kidney Disease: Global Dimension and Perspectives [Published Correction Appears in Lancet. 2013 Jul 20; 382(9888): 208]. The Lancet, 382, 260-272.
[Google Scholar] [CrossRef
[2] 中国医师协会肾脏内科医师分会肾性贫血指南工作组. 中国肾性贫血诊治临床实践指南[J]. 中华医学杂志, 2021, 101(20): 1463-1502.
[3] Ogawa, C., Tsuchiya, K., Maeda, K. and Nitta, K. (2018) Renal Anemia and Iron Metabolism. Contributions to Nephrology, 195, 62-73.
[Google Scholar] [CrossRef] [PubMed]
[4] KDOQI, National Kidney Foundation (2006) KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease [Published Correction Appears in Am J Kidney Dis. 2006 Sep; 48(3): 518]. American Journal of Kidney Diseases, 47, S11-S145.
[5] Gafter-Gvili, A., Schechter, A. and Rozen-Zvi, B. (2019) Iron Deficiency Anemia in Chronic Kidney Disease. Acta Haematologica, 142, 44-50.
[Google Scholar] [CrossRef] [PubMed]
[6] Ratcliffe, L.E., Thomas, W., Glen, J., et al. (2016) Diagnosis and Management of Iron Deficiency in CKD: A Summary of the NICE Guideline Recommendations and Their Rationale. American Journal of Kidney Diseases, 67, 548-558.
[Google Scholar] [CrossRef] [PubMed]
[7] Ganz, T. and Nemeth, E. (2012) Hepcidin and Iron Homeostasis. Biochimica et Biophysica Acta, 1823, 1434-1443.
[Google Scholar] [CrossRef] [PubMed]
[8] Krause, A., Neitz, S., Mägert, H.J., et al. (2000) LEAP-1, a Novel Highly Disulfide-Bonded Human Peptide, Exhibits Antimicrobial Activity. FEBS Letters, 480, 147-150.
[Google Scholar] [CrossRef
[9] Park, C.H., Valore, E.V., Waring, A.J. and Ganz, T. (2001) Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver. Journal of Biological Chemistry, 276, 7806-7810.
[Google Scholar] [CrossRef
[10] Hunter, H.N., Fulton, D.B., Ganz, T. and Vogel, H.J. (2002) The Solution Structure of Human Hepcidin, a Peptide Hormone with Antimicrobial Activity That Is Involved in Iron Uptake and Hereditary Hemochromatosis. Journal of Biological Chemistry, 277, 37597-37603.
[Google Scholar] [CrossRef
[11] Zhang, D.L. and Rouault, T.A. (2018) How Does Hepcidin Hinder Ferroportin Activity? Blood, 131, 840-842.
[Google Scholar] [CrossRef] [PubMed]
[12] Ueda, N. and Takasawa, K. (2017) Role of Hepcidin-25 in Chronic Kidney Disease: Anemia and Beyond. Current Medicinal Chemistry, 24, 1417-1452.
[Google Scholar] [CrossRef] [PubMed]
[13] Core, A.B., Canali, S. and Babitt, J.L. (2014) Hemojuvelin and Bone Morphogenetic Protein (BMP) Signaling in Iron Homeostasis. Frontiers in Pharmacology, 5, Article No. 104.
[Google Scholar] [CrossRef] [PubMed]
[14] Uehata, T., Tomosugi, N., Shoji, T., et al. (2012) Serum Hepcidin-25 Levels and Anemia in Non-Dialysis Chronic Kidney Disease Patients: A Cross-Sectional Study. Nephrology Dialysis Transplantation, 27, 1076-1083.
[Google Scholar] [CrossRef] [PubMed]
[15] Rodriguez, R., Jung, C.L., Gabayan, V., et al. (2014) Hepcidin Induction by Pathogens and Pathogen-Derived Molecules Is Strongly Dependent on Interleukin-6. Infection and Immunity, 82, 745-752.
[Google Scholar] [CrossRef
[16] Łukaszyk, E., Łukaszyk, M., Koc-Żórawska, E., et al. (2015) Iron Status and Inflammation in Early Stages of Chronic Kidney Disease. Kidney and Blood Pressure Research, 40, 366-373.
[Google Scholar] [CrossRef] [PubMed]
[17] Nemeth, E., Rivera, S., Gabayan, V., et al. (2004) IL-6 Mediates Hypoferremia of Inflammation by Inducing the Synthesis of the Iron Regulatory Hormone Hepcidin. Journal of Clinical Investigation, 113, 1271-1276.
[Google Scholar] [CrossRef
[18] Nai, A., Rubio, A., Campanella, A., et al. (2016) Limiting Hepatic Bmp-Smad Signaling by Matriptase-2 Is Required for Erythropoietin-Mediated Hepcidin Suppression in Mice. Blood, 127, 2327-2336.
[Google Scholar] [CrossRef] [PubMed]
[19] Shanmugam, N.K., Chen, K. and Cherayil, B.J. (2015) Commensal Bacteria-Induced Interleukin 1β (IL-1β) Secreted by Macrophages Up-Regulates Hepcidin Expression in Hepatocytes by Activating the Bone Morphogenetic Protein Signaling Pathway. Journal of Biological Chemistry, 290, 30637-30647.
[Google Scholar] [CrossRef
[20] Ueda, N. and Takasawa, K. (2018) Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease. Nutrients, 10, 1173.
[Google Scholar] [CrossRef] [PubMed]
[21] Shoji, S., Inaba, M., Tomosugi, N., et al. (2013) Greater Potency of Darbepoetin-α than Erythropoietin in Suppression of Serum Hepcidin-25 and Utilization of Iron for Erythropoiesis in Hemodialysis Patients. European Journal of Haematology, 90, 237-244.
[Google Scholar] [CrossRef] [PubMed]
[22] Swinkels, D.W., Girelli, D., Laarakkers, C., et al. (2008) Advances in Quantitative Hepcidin Measurements by Time-of-Flight Mass Spectrometry. PLoS ONE, 3, e2706.
[Google Scholar] [CrossRef] [PubMed]
[23] Troutt, J.S., Butterfield, A.M. and Konrad, R.J. (2013) Hepcidin-25 Concentrations Are Markedly Increased in Patients with Chronic Kidney Disease and Are Inversely Correlated with Estimated Glomerular Filtration Rates. Journal of Clinical Laboratory Analysis, 27, 504-510.
[Google Scholar] [CrossRef] [PubMed]
[24] Nicolas, G., Chauvet, C., Viatte, L., et al. (2002) The Gene Encoding the Iron Regulatory Peptide Hepcidin Is Regulated by Anemia, Hypoxia, and Inflammation. Journal of Clinical Investigation, 110, 1037-1044.
[Google Scholar] [CrossRef
[25] Semenza, G.L. (2000) HIF-1: Mediator of Physiological and Pathophysiological Responses to Hypoxia. Journal of Applied Physiology (1985), 88, 1474-1480.
[Google Scholar] [CrossRef] [PubMed]
[26] Liu, Q., Davidoff, O., Niss, K. and Haase, V.H. (2012) Hypoxia-Inducible Factor Regulates Hepcidin via Erythropoietin-Induced Erythropoiesis. Journal of Clinical Investigation, 122, 4635-4644.
[Google Scholar] [CrossRef
[27] Pasricha, S.R., McHugh, K. and Drakesmith, H. (2016) Regulation of Hepcidin by Erythropoiesis: The Story So Far. Annual Review of Nutrition, 36, 417-434.
[Google Scholar] [CrossRef] [PubMed]
[28] Kautz, L., Jung, G., Valore, E.V., Rivella, S., Nemeth, E. and Ganz, T. (2014) Identification of Erythroferrone as an Erythroid Regulator of Iron Metabolism [Published Correction Appears in Nat Genet. 2020 Apr; 52(4): 463]. Nature Genetics, 46, 678-684.
[Google Scholar] [CrossRef] [PubMed]
[29] Bacchetta, J., Zaritsky, J.J., Sea, J.L., et al. (2014) Suppression of Iron-Regulatory Hepcidin by Vitamin D. Journal of the American Society of Nephrology, 25, 564-572.
[Google Scholar] [CrossRef
[30] Schödel, J. and Ratcliffe, P.J. (2019) Mechanisms of Hypoxia Signalling: New Implications for Nephrology. Nature Reviews Nephrology, 15, 641-659.
[Google Scholar] [CrossRef] [PubMed]
[31] Haase, V.H. (2017) HIF-Prolyl Hydroxylases as Therapeutic Targets in Erythropoiesis and Iron Metabolism. Hemodialysis International, 21, S110-S124.
[Google Scholar] [CrossRef] [PubMed]
[32] Bruick, R.K. and McKnight, S.L. (2001) A Conserved Family of Prolyl-4-hydroxylases That Modify HIF. Science, 294, 1337-1340.
[Google Scholar] [CrossRef] [PubMed]
[33] Dhillon, S. (2019) Roxadustat: First Global Approval. Drugs, 79, 563-572.
[Google Scholar] [CrossRef] [PubMed]
[34] Barratt, J., Sulowicz, W., Schömig, M., et al. (2021) Efficacy and Cardiovascular Safety of Roxadustat in Dialysis-Dependent Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. Advances in Therapy, 38, 5345-5360.
[Google Scholar] [CrossRef] [PubMed]
[35] Akizawa, T., Iwasaki, M., Otsuka, T., Yamaguchi, Y. and Reusch, M. (2021) Phase 3 Study of Roxadustat to Treat Anemia in Non-Dialysis-Dependant CKD. Kidney International Reports, 6, 1810-1828.
[Google Scholar] [CrossRef] [PubMed]
[36] Wish, J.B., Eckardt, K.U., Kovesdy, C.P., Fishbane, S., Spinowitz, B.S. and Berns, J.S. (2021) Hypoxia-Inducible Factor Stabilization as an Emerging Therapy for CKD-Related Anemia: Report from a Scientific Workshop Sponsored by the National Kidney Foundation. American Journal of Kidney Diseases, 78, 709-718.
[Google Scholar] [CrossRef] [PubMed]
[37] Dhillon, S. (2020) Daprodustat: First Approval. Drugs, 80, 1491-1497.
[Google Scholar] [CrossRef] [PubMed]
[38] Markham, A. (2020) Vadadustat: First Approval. Drugs, 80, 1365-1371.
[Google Scholar] [CrossRef] [PubMed]
[39] Markham, A. (2021) Enarodustat: First Approval. Drugs, 81, 169-174.
[Google Scholar] [CrossRef] [PubMed]
[40] Singh, A.K., Carroll, K., Perkovic, V., et al. (2021) Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. The New England Journal of Medicine, 385, 2325-2335.
[Google Scholar] [CrossRef
[41] Singh, A.K., Carroll, K., McMurray, J.J.V., et al. (2021) Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis. The New England Journal of Medicine, 385, 2313-2324.
[Google Scholar] [CrossRef
[42] Akizawa, T., Nobori, K., Matsuda, Y., et al. (2021) Molidustat for the Treatment of Anemia in Japanese Patients Undergoing Peritoneal Dialysis: A Single-Arm, Open-Label, Phase 3 Study [Published Online Ahead of Print, 2021 Jul 26]. Therapeutic Apheresis and Dialysis.
[Google Scholar] [CrossRef] [PubMed]
[43] Akizawa, T., Yamada, T., Nobori, K., et al. (2021) Molidustat for Japanese Patients with Renal Anemia Receiving Dialysis. Kidney International Reports, 6, 2604-2616.
[Google Scholar] [CrossRef] [PubMed]
[44] Yap, D.Y.H., McMahon, L.P., Hao, C.M., et al. (2021) Recommendations by the Asian Pacific Society of Nephrology (APSN) on the Appropriate Use of HIF-PH Inhibitors. Nephrology (Carlton), 26, 105-118.
[Google Scholar] [CrossRef] [PubMed]
[45] Locatelli, F., Del Vecchio, L. and Luise, M.C. (2017) Current and Future Chemical Therapies for Treating Anaemia in Chronic Kidney Disease. Expert Opinion on Pharmacotherapy, 18, 781-788.
[Google Scholar] [CrossRef] [PubMed]
[46] Jelkmann, W. (2018) Activin Receptor Ligand Traps in Chronic Kidney Disease. Current Opinion in Nephrology and Hypertension, 27, 351-357.
[Google Scholar] [CrossRef