{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:56:30Z","timestamp":1791950190948,"version":"4.3.4"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The trace element zinc is essential for diverse physiological processes in humans. Zinc deficiency can impair growth, skin reproduction, immune function, maintenance of taste, glucose metabolism, and neurological function. Patients with chronic kidney disease (CKD) are susceptible to zinc deficiency, which is associated with erythropoiesis-stimulating agent (ESA) hypo-responsive anemia, nutritional problems, and cardiovascular diseases as well as non-specific symptoms such as dermatitis, prolonged wound healing, taste disturbance, appetite loss, or cognitive decline. Thus, zinc supplementation may be useful for the treatment of its deficiency, although it often causes copper deficiency, which is characterized by several severe disorders including cytopenia and myelopathy. In this review article, we mainly discuss the significant roles of zinc and the association between zinc deficiency and the pathogenesis of complications in patients with CKD.<\/jats:p>","DOI":"10.3390\/jcm12041667","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T02:02:09Z","timestamp":1676858529000},"page":"1667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Clinical Significance of Trace Element Zinc in Patients with Chronic Kidney Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Hirotaka","family":"Fukasawa","sequence":"first","affiliation":[{"name":"Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata 438-8550, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Furuya","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata 438-8550, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata 438-8550, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Nakagami","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata 438-8550, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Ishino","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata 438-8550, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Kitamoto","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata 438-8550, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyosuke","family":"Omata","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata 438-8550, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yasuda","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/156482650102200201","article-title":"The importance of zinc in human nutrition and estimation of the global prevalence of zinc defi ciency","volume":"22","author":"Kenneth","year":"2001","journal-title":"Food Nutr. Bull."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1500S","DOI":"10.1093\/jn\/130.5.1500S","article-title":"The role of zinc in growth and cell proliferation","volume":"130","author":"MacDonald","year":"2000","journal-title":"J. Nutr."},{"key":"ref_3","first-page":"144","article-title":"Zinc and its importance for human health: An integrative review","volume":"18","author":"Roohani","year":"2013","journal-title":"J. Res. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Shi, Y., Zou, Y., Shen, Z., Xiong, Y., Zhang, W., Liu, C., and Chen, S. (2020). Trace Elements, PPARs, and Metabolic Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072612"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113877","DOI":"10.1016\/j.ejmech.2021.113877","article-title":"Zinc enzymes in medicinal chemistry","volume":"226","author":"Hou","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1681\/ASN.2017050492","article-title":"Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-kappaB","volume":"29","author":"Voelkl","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10787-017-0309-4","article-title":"Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-kappaB signaling","volume":"25","author":"Jarosz","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1097\/MCO.0b013e3283312956","article-title":"Zinc: Role in immunity, oxidative stress and chronic inflammation","volume":"12","author":"Prasad","year":"2009","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Prasad, A.S., and Bao, B. (2019). Molecular Mechanisms of Zinc as a Pro-Antioxidant Mediator: Clinical Therapeutic Implications. Antioxidants, 8.","DOI":"10.3390\/antiox8060164"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.hlc.2017.07.009","article-title":"Prevalence of Zinc Deficiency in Cardiac Surgery Patients","volume":"27","author":"Braun","year":"2018","journal-title":"Heart Lung Circ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/aps.2018.25","article-title":"Zinc deficiency and cellular oxidative stress: Prognostic implications in cardiovascular diseases","volume":"39","author":"Choi","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0899-9007(00)00469-X","article-title":"Recognition of zinc-deficiency syndrome","volume":"17","author":"Prasad","year":"2001","journal-title":"Nutrition"},{"key":"ref_14","first-page":"103","article-title":"Zinc deficiency: Its characterization and treatment","volume":"41","author":"Prasad","year":"2004","journal-title":"Met. Ions Biol. Syst."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kodama, H., Tanaka, M., Naito, Y., Katayama, K., and Moriyama, M. (2020). Japan\u2019s Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082941"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0969-806X(97)00202-8","article-title":"Reevaluation of the trace element content in reference man","volume":"51","author":"Iyengar","year":"1998","journal-title":"Radiat. Phys. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1374S","DOI":"10.1093\/jn\/130.5.1374S","article-title":"Overview of zinc absorption and excretion in the human gastrointestinal tract","volume":"130","author":"Krebs","year":"2000","journal-title":"J. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/ndt\/gfz065","article-title":"Renal handling of zinc in chronic kidney disease patients and the role of circulating zinc levels in renal function decline","volume":"35","author":"Damianaki","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1136\/bmj.330.7487.347","article-title":"Zinc deficiency: What are the most appropriate interventions?","volume":"330","author":"Shrimpton","year":"2005","journal-title":"BMJ"},{"key":"ref_20","first-page":"128","article-title":"Changes in levels of copper, iron, zinc, and selenium in patients at different stages of chronic kidney disease","volume":"4","author":"Shih","year":"2012","journal-title":"Genom. Med. Biomark. Health Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s12011-018-1314-1","article-title":"Changes in Trace Elements During Early Stages of Chronic Kidney Disease in Type 2 Diabetic Patients","volume":"186","author":"Lin","year":"2018","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12011-008-8135-6","article-title":"Trace element status of chronic renal patients undergoing hemodialysis","volume":"124","author":"Kiziltas","year":"2008","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tonelli, M., Wiebe, N., Hemmelgarn, B., Klarenbach, S., Field, C., Manns, B., Thadhani, R., Gill, J., and Alberta Kidney Disease, N. (2009). Trace elements in hemodialysis patients: A systematic review and meta-analysis. BMC Med., 7.","DOI":"10.1186\/1741-7015-7-25"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Toida, T., Toida, R., Ebihara, S., Takahashi, R., Komatsu, H., Uezono, S., Sato, Y., and Fujimoto, S. (2020). Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients. Nutrients, 12.","DOI":"10.3390\/nu12103187"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.5414\/CNP73030","article-title":"Metal ion and vitamin adsorption profiles of phosphate binder ion-exchange resins","volume":"73","author":"Takagi","year":"2010","journal-title":"Clin. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1053\/jren.2002.29597","article-title":"Iron and zinc status of patients with chronic renal failure who are not on dialysis","volume":"12","author":"Mafra","year":"2002","journal-title":"J. Ren. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1385\/BTER:112:1:1","article-title":"Effect of end-stage renal disease and diabetes on zinc and copper status","volume":"112","author":"Batista","year":"2006","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/ndt\/gfg021","article-title":"Haematocrit and the risk of developing end-stage renal disease","volume":"18","author":"Iseki","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1111\/j.1523-1755.2005.00693.x","article-title":"Anemia and mortality in hemodialysis patients: Accounting for morbidity and treatment variables updated over time","volume":"68","author":"Robinson","year":"2005","journal-title":"Kidney Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s41100-017-0114-y","article-title":"2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease","volume":"3","author":"Yamamoto","year":"2017","journal-title":"Renal. Replace. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.kint.2021.03.020","article-title":"Controversies in optimal anemia management: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference","volume":"99","author":"Babitt","year":"2021","journal-title":"Kidney Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1744-9987.2009.00656.x","article-title":"Zinc deficiency anemia and effects of zinc therapy in maintenance hemodialysis patients","volume":"13","author":"Fukushima","year":"2009","journal-title":"Ther. Apher. Dial."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.3390\/nu7053783","article-title":"Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis","volume":"7","author":"Kobayashi","year":"2015","journal-title":"Nutrients"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1038\/sj.emboj.7600248","article-title":"Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1","volume":"23","author":"Suzuki","year":"2004","journal-title":"EMBO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1038\/sj.emboj.7600274","article-title":"Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2","volume":"23","author":"Anguita","year":"2004","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1182\/blood-2009-09-241752","article-title":"Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage","volume":"115","author":"Laurent","year":"2010","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1681\/ASN.V651329","article-title":"Nutrition and mortality in hemodialysis","volume":"6","author":"Bergstrom","year":"1995","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1046\/j.1523-1755.1999.00615.x","article-title":"Body weight-for-height relationships predict mortality in maintenance hemodialysis patients","volume":"56","author":"Kopple","year":"1999","journal-title":"Kidney Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000182627","article-title":"Mortality risk factors in patients treated by chronic hemodialysis. Report of the Diaphane collaborative study","volume":"31","author":"Degoulet","year":"1982","journal-title":"Nephron"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1093\/ndt\/16.12.2386","article-title":"Body mass index and mortality in \u2018healthier\u2019 as compared with \u2018sicker\u2019 haemodialysis patients: Results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)","volume":"16","author":"Leavey","year":"2001","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1056\/NEJM199910073411501","article-title":"Body-mass index and mortality in a prospective cohort of U.S. adults","volume":"341","author":"Calle","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/00002480-200101000-00016","article-title":"Risk factor paradox in hemodialysis: Better nutrition as a partial explanation","volume":"47","author":"Fleischmann","year":"2001","journal-title":"ASAIO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1046\/j.1523-1755.2003.00803.x","article-title":"Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients","volume":"63","author":"Block","year":"2003","journal-title":"Kidney Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1097\/01.ASN.0000083905.72794.E6","article-title":"Effects of body size and body composition on survival in hemodialysis patients","volume":"14","author":"Beddhu","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1053\/j.jrn.2015.10.005","article-title":"Body Composition and Mortality Predictors in Hemodialysis Patients","volume":"26","author":"Caetano","year":"2016","journal-title":"J. Ren. Nutr."},{"key":"ref_46","first-page":"159","article-title":"Effect of zinc supplementation on body mass index and serum levels of zinc and leptin in pediatric hemodialysis patients","volume":"8","author":"Ibrahim","year":"2015","journal-title":"Int. J. Nephrol. Renovasc. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jtemb.2013.09.001","article-title":"Effects of zinc supplementation on serum zinc and leptin levels, BMI, and body composition in hemodialysis patients","volume":"28","author":"Argani","year":"2014","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fukasawa, H., Niwa, H., Ishibuchi, K., Kaneko, M., Iwakura, T., Yasuda, H., and Furuya, R. (2020). The Impact of Serum Zinc Levels on Abdominal Fat Mass in Hemodialysis Patients. Nutrients, 12.","DOI":"10.3390\/nu12030656"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.5713\/ajas.2013.13179","article-title":"Zinc-chelated Vitamin C Stimulates Adipogenesis of 3T3-L1 Cells","volume":"26","author":"Ghosh","year":"2013","journal-title":"Asian-Australas J. Anim. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Huang, X., Jiang, D., Zhu, Y., Fang, Z., Che, L., Lin, Y., Xu, S., Li, J., Huang, C., and Zou, Y. (2017). Chronic High Dose Zinc Supplementation Induces Visceral Adipose Tissue Hypertrophy without Altering Body Weight in Mice. Nutrients, 9.","DOI":"10.3390\/nu9101138"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12011-014-0078-5","article-title":"Supplementation dietary zinc levels on growth performance, carcass traits, and intramuscular fat deposition in weaned piglets","volume":"161","author":"Zhang","year":"2014","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/BF02789454","article-title":"Zinc supplementation aggravates body fat accumulation in genetically obese mice and dietary-obese mice","volume":"52","author":"Chen","year":"1996","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s12011-009-8504-9","article-title":"Zinc deficiency in chronic kidney disease: Is there a relationship with adipose tissue and atherosclerosis?","volume":"135","author":"Lobo","year":"2010","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"680","DOI":"10.3109\/0886022X.2013.789960","article-title":"Reduced plasma zinc levels, lipid peroxidation, and inflammation biomarkers levels in hemodialysis patients: Implications to cardiovascular mortality","volume":"35","author":"Lobo","year":"2013","journal-title":"Ren. Fail."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"654","DOI":"10.2215\/CJN.07450714","article-title":"Vascular calcification in patients with nondialysis CKD over 3 years","volume":"10","author":"Gorriz","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s40620-015-0260-7","article-title":"Abdominal aortic calcification in patients with CKD","volume":"30","author":"Peeters","year":"2017","journal-title":"J. Nephrol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"939","DOI":"10.7150\/ijms.32629","article-title":"Assessment of abdominal aortic calcification by computed tomography for prediction of latent left ventricular stiffness and future cardiovascular risk in pre-dialysis patients with chronic kidney disease: A single center cross-sectional study","volume":"16","author":"Furusawa","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"F891","DOI":"10.1152\/ajprenal.00163.2014","article-title":"A current understanding of vascular calcification in CKD","volume":"307","author":"Paloian","year":"2014","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.kint.2017.04.006","article-title":"Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: What\u2019s changed and why it matters","volume":"92","author":"Ketteler","year":"2017","journal-title":"Kidney Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e1040","DOI":"10.1038\/cddis.2013.547","article-title":"Zinc depletion regulates the processing and secretion of IL-1beta","volume":"5","author":"Summersgill","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.3892\/mmr.2017.7236","article-title":"Zinc inhibits high glucose-induced NLRP3 inflammasome activation in human peritoneal mesothelial cells","volume":"16","author":"Fan","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mrfmmm.2009.09.007","article-title":"A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders","volume":"690","author":"Kim","year":"2010","journal-title":"Mutat. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s40620-014-0162-0","article-title":"Systemic inflammation and oxidative stress in hemodialysis patients are associated with down-regulation of Nrf2","volume":"28","author":"Pedruzzi","year":"2015","journal-title":"J. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1024769","DOI":"10.1155\/2017\/1024769","article-title":"Effect of Zinc Supplementation on Maintenance Hemodialysis Patients: A Systematic Review and Meta-Analysis of 15 Randomized Controlled Trials","volume":"2017","author":"Wang","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1080\/17474086.2022.2142113","article-title":"Copper deficiency, a rare but correctable cause of pancytopenia: A review of literature","volume":"15","author":"Tahir","year":"2022","journal-title":"Expert. Rev. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Nishime, K., Kondo, M., Saito, K., Miyawaki, H., and Nakagawa, T. (2020). Zinc Burden Evokes Copper Deficiency in the Hypoalbuminemic Hemodialysis Patients. Nutrients, 12.","DOI":"10.3390\/nu12020577"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1001\/jama.1978.03290200044019","article-title":"Hypocupremia induced by zinc therapy in adults","volume":"240","author":"Prasad","year":"1978","journal-title":"JAMA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/0016-5085(88)90445-3","article-title":"Zinc-induced copper deficiency","volume":"94","author":"Hoffman","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.4065\/81.10.1371","article-title":"Copper deficiency myelopathy (human swayback)","volume":"81","author":"Kumar","year":"2006","journal-title":"Mayo Clin. Proc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2169\/internalmedicine.45.1541","article-title":"Correction of copper deficiency improves erythropoietin unresponsiveness in hemodialysis patients with anemia","volume":"45","author":"Higuchi","year":"2006","journal-title":"Intern. Med."},{"key":"ref_71","first-page":"79","article-title":"Copper deficiency myelopathy secondary to parenteral zinc supplementation during chronic dialysis","volume":"24","author":"Rissardo","year":"2019","journal-title":"Neurol. Asia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000512612","article-title":"Erythropoietin-Resistant Anemia Secondary to Zinc-Induced Hypocupremia in a Hemodialysis Patient","volume":"11","author":"Munie","year":"2021","journal-title":"Case Rep. Nephrol. Dial."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13045-018-0645-x","article-title":"The roles of metallothioneins in carcinogenesis","volume":"11","author":"Si","year":"2018","journal-title":"J. Hematol. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1667\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:36:43Z","timestamp":1760121403000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,20]]},"references-count":73,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041667"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041667","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,20]]}}}