Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children63110.24287/1726-1708-2023-22-3-130-135ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИAssessment of erythroferrone levels in children with chronic kidney disease on regular hemodialysisAssessment of erythroferrone levels in children with chronic kidney disease on regular hemodialysisEl-HawyMahmoud Ahmed
Egypt

Pediatrics Department, Faculty of Medicine

Menoufia

Mahmoud Ahmed El-Hawy - Department of Pediatrics, Faculty of Medicine.

Shebin El Kom, 32511 Menoufia

mahmodelhawy18@yahoo.comNowirAhmed AdelNowirAhmed Adel Mahmoud
Egypt

Pediatrics Department, Faculty of Medicine

Menoufia

Menoufia

Nowir@yahoo.comZakiShimaa AbdelsatarZakiShimaa Abdelsatar Refat
Egypt

Clinical Biochemistry and Molecular Diagnostics Department

Menoufia

Menoufia

Shimaa@yahoo.comEl-HaruonMohamed Shokry
Egypt

Pediatrics Department, Faculty of Medicine

Menoufia

Menoufia

Mohamed@yahoo.comMenoufia UniversityNational Liver Institute, Menoufia University031020232231301350607202218072022Copyright ©; 2023, «D. Rogachev NMRCPHOI»Copyright ©; 2023, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2023«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/631

Anemia is a common comorbidity in children with chronic kidney disease (CKD) and is associated with adverse outcomes. Erythroferrone (ERFE) is a hepcidin inhibitor whose synthesis is stimulated by erythropoietin, which increases iron absorption and mobilization. Aim of the study: to assess the levels of ERFE hormone in children with CKD on regular hemodialysis. This case–control study was carried out at Menoufia University Hospital and included 70 subjects: 38 healthy individuals (controls) and 32 children with CKD on regular dialysis (cases). The study was approved by the Faculty of Medicine Ethics Committee at Menoufia University. All children were subjected to full history taking, complete clinical examination, blood tests such as complete blood count, reticulocyte count, serum iron, ferritin, and total iron binding capacity, liver and renal function tests, and an immunoassay to measure human ERFE. There was a statistically significant difference in the levels of ERFE between the cases and controls (p < 0.001). There was a significant, strong correlation between the levels of hemoglobin and serum iron and the level of ERFE (r = –0.655, p < 0.001). There was no significant correlation between the administered dose of exogenous erythropoietin and the level of ERFE (p = 0.460). Serum ERFE levels in the children with CKD on regular hemodialysis were significantly higher than in the controls and were negatively correlated with hemoglobin and iron levels. There was no significant correlation between ERFE levels and both serum ferritin and total iron binding capacity levels.

Anemia is a common comorbidity in children with chronic kidney disease (CKD) and is associated with adverse outcomes. Erythroferrone (ERFE) is a hepcidin inhibitor whose synthesis is stimulated by erythropoietin, which increases iron absorption and mobilization. Aim of the study: to assess the levels of ERFE hormone in children with CKD on regular hemodialysis. This case–control study was carried out at Menoufia University Hospital and included 70 subjects: 38 healthy individuals (controls) and 32 children with CKD on regular dialysis (cases). The study was approved by the Faculty of Medicine Ethics Committee at Menoufia University. All children were subjected to full history taking, complete clinical examination, blood tests such as complete blood count, reticulocyte count, serum iron, ferritin, and total iron binding capacity, liver and renal function tests, and an immunoassay to measure human ERFE. There was a statistically significant difference in the levels of ERFE between the cases and controls (p < 0.001). There was a significant, strong correlation between the levels of hemoglobin and serum iron and the level of ERFE (r = –0.655, p < 0.001). There was no significant correlation between the administered dose of exogenous erythropoietin and the level of ERFE (p = 0.460). Serum ERFE levels in the children with CKD on regular hemodialysis were significantly higher than in the controls and were negatively correlated with hemoglobin and iron levels. There was no significant correlation between ERFE levels and both serum ferritin and total iron binding capacity levels.

anemiachronic kidney diseaseerythroferronehemodialysisanemiachronic kidney diseaseerythroferronehemodialysisNot specified1. Abbaspour N., Hurrell R., Kelishadi R. Review on iron and its importance for human health. J Res Med Sci 2014; 19 (2): 164.Abbaspour N., Hurrell R., Kelishadi R. Review on iron and its importance for human health. J Res Med Sci 2014; 19 (2): 164.2. Rishi G., Wallace D.F., Subramaniam V.N. Hepcidin: regulation of the master iron regulator. Biosci Rep 2015; 35 (3): e00192. DOI: 10.1042/BSR20150014Rishi G., Wallace D.F., Subramaniam V.N. Hepcidin: regulation of the master iron regulator. Biosci Rep 2015; 35 (3): e00192. DOI: 10.1042/BSR201500143. Kautz L., Jung G., Valore E.V., Rivella S., Nemeth E., Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014; 46 (7): 678–84.Kautz L., Jung G., Valore E.V., Rivella S., Nemeth E., Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014; 46 (7): 678–84.4. Seldin M.M., Peterson J.M., Byerly M.S., Wei Z., Wong G.W. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012; 287 (15): 11968–80.Seldin M.M., Peterson J.M., Byerly M.S., Wei Z., Wong G.W. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012; 287 (15): 11968–80.5. Astor B.C., Muntner P., Levin A., Eustace J.A., Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994). Arch Int Med 2002; 162 (12): 1401–8.Astor B.C., Muntner P., Levin A., Eustace J.A., Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994). Arch Int Med 2002; 162 (12): 1401–8.6. Panwar B., Gutiérrez O.M. Disorders of iron metabolism and anemia in chronic kidney disease. Semin Nephrol 2016; 36 (4): 252–61. DOI: 10.1016/j.semnephrol.2016.05.002Panwar B., Gutiérrez O.M. Disorders of iron metabolism and anemia in chronic kidney disease. Semin Nephrol 2016; 36 (4): 252–61. DOI: 10.1016/j.semnephrol.2016.05.0027. Crowson C.S., Rollefstad S., Ikdahl E., Kitas G.D., Van Riel P.L., Gabriel S.E., et al. Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis 2018; 77 (1): 48–54.Crowson C.S., Rollefstad S., Ikdahl E., Kitas G.D., Van Riel P.L., Gabriel S.E., et al. Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis 2018; 77 (1): 48–54.8. Libby P., Buring J.E., Badimon L., Hansson G.K., Deanfield J., Bittencourt M.S., et al. Atherosclerosis. Nat Rev Dis Primers 2019; 5 (1): 56. DOI: 10.1038/s41572-019-0106-zLibby P., Buring J.E., Badimon L., Hansson G.K., Deanfield J., Bittencourt M.S., et al. Atherosclerosis. Nat Rev Dis Primers 2019; 5 (1): 56. DOI: 10.1038/s41572-019-0106-z9. Raichoudhury R. Spinowitz B.S. Treatment of anemia in difficult-to-manage patients with chronic kidney disease. Kidney Int Suppl 2021; 11 (1): 26–34.Raichoudhury R. Spinowitz B.S. Treatment of anemia in difficult-to-manage patients with chronic kidney disease. Kidney Int Suppl 2021; 11 (1): 26–34.10. Atkinson M.A., Warady B.A. Anemia in chronic kidney disease. Pediatr Nephrol 2018; 33 (2): 227–38.Atkinson M.A., Warady B.A. Anemia in chronic kidney disease. Pediatr Nephrol 2018; 33 (2): 227–38.11. Spoto B., Pizzini P., Torino C., Leonardis D., Cutrupi S., Tripepi G., et al. FP379 Erythroferrone Predicts Mortality and Cardiovascular Events in CKD and in Hemodialysis Patients: A Two Cohorts Study. Nephrol Dial Transplant 2019; 34 (Suppl_1): p.gfz106. FP379.Spoto B., Pizzini P., Torino C., Leonardis D., Cutrupi S., Tripepi G., et al. FP379 Erythroferrone Predicts Mortality and Cardiovascular Events in CKD and in Hemodialysis Patients: A Two Cohorts Study. Nephrol Dial Transplant 2019; 34 (Suppl_1): p.gfz106. FP379.12. Kuriyama S., Maruyama Y., Honda H. A new insight into the treatment of renal anemia with HIF stabilizer. Renal Replacement Therapy 2020; 6 (1): 1–14.Kuriyama S., Maruyama Y., Honda H. A new insight into the treatment of renal anemia with HIF stabilizer. Renal Replacement Therapy 2020; 6 (1): 1–14.13. Allen R.P., Picchietti D.L., Auerbach M., Cho Y.W., Connor J.R., Earley C.J., et al. Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report. Sleep Med 2018; 41: 27–44.Allen R.P., Picchietti D.L., Auerbach M., Cho Y.W., Connor J.R., Earley C.J., et al. Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report. Sleep Med 2018; 41: 27–44.14. Ogawa C., Tsuchiya K., Kanda F., Maeda T. Low levels of serum ferritin lead to adequate hemoglobin levels and good survival in hemodialysis patients. Am J Nephrol 2014; 40 (6): 561–70.Ogawa C., Tsuchiya K., Kanda F., Maeda T. Low levels of serum ferritin lead to adequate hemoglobin levels and good survival in hemodialysis patients. Am J Nephrol 2014; 40 (6): 561–70.15. Yu P.-H., Lin M.-Y., Chiu Y.-W., Lee J.-J., Hwang S.-J., Hung C.-C., Chen H.-C. Low serum iron is associated with anemia in CKD stage 1–4 patients with normal transferrin saturations. Sci Rep 2021; 11 (1): 1–10.Yu P.-H., Lin M.-Y., Chiu Y.-W., Lee J.-J., Hwang S.-J., Hung C.-C., Chen H.-C. Low serum iron is associated with anemia in CKD stage 1–4 patients with normal transferrin saturations. Sci Rep 2021; 11 (1): 1–10.16. Hanudel M.R., Rappaport M., Chua K., Gabayan V., Qiao B., Jung G., et al. Levels of the erythropoietin-responsive hormone erythroferrone in mice and humans with chronic kidney disease. Haematologica 2018; 103 (4): e141.Hanudel M.R., Rappaport M., Chua K., Gabayan V., Qiao B., Jung G., et al. Levels of the erythropoietin-responsive hormone erythroferrone in mice and humans with chronic kidney disease. Haematologica 2018; 103 (4): e141.17. Van der Weerd N.C., Grooteman M.P., Bots M.L., van den Dorpel M.A., den Hoedt C.H., Mazairac A.H., et al. Hepcidin-25 is related to cardiovascular events in chronic haemodialysis patients. Nephrol Dial Transplant 2013; 28 (12): 3062–71.Van der Weerd N.C., Grooteman M.P., Bots M.L., van den Dorpel M.A., den Hoedt C.H., Mazairac A.H., et al. Hepcidin-25 is related to cardiovascular events in chronic haemodialysis patients. Nephrol Dial Transplant 2013; 28 (12): 3062–71.18. Honda H., Kobayashi Y., Onuma S., Shibagaki K., Yuza T., Hirao K., et al. Associations among erythroferrone and biomarkers of erythropoiesis and iron metabolism, and treatment with long-term erythropoiesis-stimulating agents in patients on hemodialysis. PLoS One 2016; 11 (3): e0151601.Honda H., Kobayashi Y., Onuma S., Shibagaki K., Yuza T., Hirao K., et al. Associations among erythroferrone and biomarkers of erythropoiesis and iron metabolism, and treatment with long-term erythropoiesis-stimulating agents in patients on hemodialysis. PLoS One 2016; 11 (3): e0151601.19. David V., Martin A., Isakova T., Spaulding C., Qi L., Ramirez V., et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int 2016; 89 (1): 135–46.David V., Martin A., Isakova T., Spaulding C., Qi L., Ramirez V., et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int 2016; 89 (1): 135–46.20. Van Vuren A.J., Eisenga M.F., van Straaten S., Glenthøj A., Gaillard C.A., Bakker S.J., et al. Interplay of erythropoietin, fibroblast growth factor 23, and erythroferrone in patients with hereditary hemolytic anemia. Blood Adv 2020; 4 (8): 1678–82.Van Vuren A.J., Eisenga M.F., van Straaten S., Glenthøj A., Gaillard C.A., Bakker S.J., et al. Interplay of erythropoietin, fibroblast growth factor 23, and erythroferrone in patients with hereditary hemolytic anemia. Blood Adv 2020; 4 (8): 1678–82.21. Clinkenbeard E.L., Hanudel M.R., Stayrook K.R., Appaiah H.N., Farrow E.G., Cass T.A., et al. Erythropoietin stimulates murine and human fibroblast growth factor-23, revealing novel roles for bone and bone marrow. Haematologica 2017; 102 (11): e427.Clinkenbeard E.L., Hanudel M.R., Stayrook K.R., Appaiah H.N., Farrow E.G., Cass T.A., et al. Erythropoietin stimulates murine and human fibroblast growth factor-23, revealing novel roles for bone and bone marrow. Haematologica 2017; 102 (11): e427.22. Bross R., Zitterkoph J., Pithia J., Benner D., Rambod M., Kovesdy C.P., et al. Association of serum total iron-binding capacity and its changes over time with nutritional and clinical outcomes in hemodialysis patients. Am J Nephrol 2009; 29 (6): 571–81.Bross R., Zitterkoph J., Pithia J., Benner D., Rambod M., Kovesdy C.P., et al. Association of serum total iron-binding capacity and its changes over time with nutritional and clinical outcomes in hemodialysis patients. Am J Nephrol 2009; 29 (6): 571–81.23. Thang L.V., Kien N.T., Van Hung N., Kien T.Q., Dung N.H., Thu Huong N.T., et al., Serum total iron-binding capacity and iron status in patients with non-dialysis-dependent chronic kidney disease: A cross-sectional study in Vietnam. Asia Pac J Clin Nutr 2020; 29 (1): 48–54.Thang L.V., Kien N.T., Van Hung N., Kien T.Q., Dung N.H., Thu Huong N.T., et al., Serum total iron-binding capacity and iron status in patients with non-dialysis-dependent chronic kidney disease: A cross-sectional study in Vietnam. Asia Pac J Clin Nutr 2020; 29 (1): 48–54.24. Ryu S.-R., Park S.K., Jung J.Y., Kim Y.H., Oh Y.K., Yoo T.H., Sung S. The prevalence and management of anemia in chronic kidney disease patients: result from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). J Korean Med Sci 2017; 32 (2): 249–56.Ryu S.-R., Park S.K., Jung J.Y., Kim Y.H., Oh Y.K., Yoo T.H., Sung S. The prevalence and management of anemia in chronic kidney disease patients: result from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). J Korean Med Sci 2017; 32 (2): 249–56.25. Kurella Tamura M., Vittinghoff E., Yang J., Go A.S., Seliger S.L., Kusek J.W., et al. Anemia and risk for cognitive decline in chronic kidney disease. BMC Nephrol 2016; 17 (1): 1–7.Kurella Tamura M., Vittinghoff E., Yang J., Go A.S., Seliger S.L., Kusek J.W., et al. Anemia and risk for cognitive decline in chronic kidney disease. BMC Nephrol 2016; 17 (1): 1–7.26. Lukaszyk E., Lukaszyk M., KocZorawska E., Bodzenta-Lukaszyk A., Malyszko J. Fibroblast growth factor 23, iron and inflammation–are they related in early stages of chronic kidney disease? Arch Med Sci 2017; 13 (4): 845.Lukaszyk E., Lukaszyk M., KocZorawska E., Bodzenta-Lukaszyk A., Malyszko J. Fibroblast growth factor 23, iron and inflammation–are they related in early stages of chronic kidney disease? Arch Med Sci 2017; 13 (4): 845.27. Alzaheb R.A., Al-Amer O. The prevalence of iron deficiency anemia and its associated risk factors among a sample of female university students in Tabuk, Saudi Arabia. Clin Med Insights Women's Health 2017; 10: 1179562X17745088.Alzaheb R.A., Al-Amer O. The prevalence of iron deficiency anemia and its associated risk factors among a sample of female university students in Tabuk, Saudi Arabia. Clin Med Insights Women's Health 2017; 10: 1179562X17745088.