Role of Hepcidin in Pediatric Chronic Kidney Disease with Anemia

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Jusli Aras
Astrid Kristina Kardani
Ninik Asmaningsih Soemaryo
Risky Vitria Prasetyo
Mohammad Sjaifullah Noer
I Dewa Gede Ugrasena

Abstract

Introduction: Anemia is a frequent complication of chronic kidney disease (CKD) in children and it causes an increase in morbidity, mortality and accelerates the rate of progression of CKD. Inflammation and impaired kidney clearance increase plasma hepcidin, inhibiting duodenal iron absorption and sequestering iron in macrophages. However, the role of hepcidin in increasing the risk of anemia in children with CKD is still uncertain. This study aimed to investigate the association between hepcidin levels and anemia in children with pre-dialysis CKD.

Methods: A cross-sectional study was conducted at Dr. Soetomo Academic Hospital from December 2018 to February 2019. Children with pre-dialysis CKD were enrolled in this study. The subject had no history of erythropoietin administration and blood transfusion 3 months before the blood sample were withdrawn. A complete blood count, ferritin serum, transferrin saturation (TSAT) and hepcidin serum were performed. The correlations between Hepcidin and ferritin level, between ferritin level and anemia, and between TSAT and anemia were analyzed using Spearman correlation and the Mann-Whitney test.


Results: A total of 47 children, 27 boys and 20 girls, ranged in age from 3 months to 18 years old. There was a significant correlation between hepcidin and ferritin levels (p=0.006) and the value of the Spearman correlation was r=0.392. While the correlation between ferritin level and anemia showed a significant result, p=0.001. However, TSAT did not show any significant correlation with anemia (p=0.230).


Conclusion: There was an indirect association between hepcidin level and anemia by increasing ferritin level that induces anemia in pre-dialysis CKD children.

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References

1. M. A. Atkinson, K. Martz, B. A. Warady, and A. M. Neu, “Risk for anemia in pediatric chronic kidney disease patients: A report of NAPRTCS,” Pediatr. Nephrol., vol. 25, no. 9, pp. 1699–1706, 2010, doi: 10.1007/s00467-010-1538-6.
2. K. Lee et al., “Anemia and Iron Deficiency in Children with Chronic Kidney Disease (CKD): Data from the Know-Ped CKD Study,” J. Clin. Med., vol. 8, no. 2, p. 152, 2019, doi: 10.3390/jcm8020152.
3. P. Saraswati et al., “Anemia in children with chronic kidney disease,” Paediatr. Indones., vol. 54, no. 4 Supplement, p. 231, 2014.
4. S. K. Sonkar et al., “Association of hepcidin and anemia in early chronic kidney disease,” Saudi J. Kidney Dis. Transpl., vol. 30, no. 2, pp. 315–324, 2019, doi: 10.4103/1319-2442.256838.
5. P. S. Suchdev et al., “Assessment of iron status in settings of inflammation: Challenges and potential approaches,” Am. J. Clin. Nutr., vol. 106, pp. 1626S-1633S, 2017, doi: 10.3945/ajcn.117.155937.
6. A. Jairam et al., “Iron status, inflammation and hepcidin in ESRD patients: The confounding role of intravenous iron therapy,” Indian J. Nephrol., vol. 20, no. 3, pp. 125–131, 2010, doi: 10.4103/0971-4065.70840.
7. J. Małyszko et al., “New parameters in iron metabolism and functional iron deficiency in patients on maintenance hemodialysis,” Pol. Arch. Med. Wewn., vol. 122, no. 11, pp. 537–542, 2012, doi: 10.20452/pamw.1458.
8. L. Mercadel et al., “The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease,” PLoS One, vol. 9, no. 6, pp. 1–7, 2014, doi: 10.1371/journal.pone.0099781.
9. E. Łukaszyk, M. Łukaszyk, E. Koc-Zórawska, J. Tobolczyk, A. Bodzenta-ŁUkaszyk, and J. Małyszko, “Iron status and inflammation in early stages of chronic kidney disease,” Kidney Blood Press. Res., vol. 40, no. 4, pp. 366–373, 2015, doi: 10.1159/000368512.
10. N. Ueda and K. Takasawa, “Impact of inflammation on ferritin, hepcidin and the management of iron deficiency anemia in chronic kidney disease,” Nutrients, vol. 10, no. 9, 2018, doi: 10.3390/nu10091173.
11. K. K. Goyal et al., “Hepcidin and proinflammatory markers in children with chronic kidney disease: A case-control study,” Clin. Nephrol., vol. 89, no. 5, pp. 363–370, 2018, doi: 10.5414/CN109132.
12. S. W. Lee et al., “Serum hepcidin and iron indices affect anemia status differently according to the kidney function of non-dialysis chronic kidney disease patients: Korean cohort study for outcome in patients with chronic kidney disease (KNOW-CKD),” Kidney Blood Press. Res., vol. 42, no. 6, pp. 1183–1192, 2017, doi: 10.1159/000485865.
13. G. D’Angelo, “Role of hepcidin in the pathophysiology and diagnosis of anemia,” Blood Res., vol. 48, no. 1, pp. 10–15, 2013, doi: 10.5045/br.2013.48.1.10.
14. G. C. Reddy, R. Devaki, and P. Rao, “Iron Indices in Patients with Functional Anemia in Chronic Kidney Disease.,” Ejifcc, vol. 24, no. 3, pp. 129–36, 2013, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/27683448%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4975187.
15. N. Zhao, A. Zhang, C. A. Enns, N. Zhao, A. Zhang, and C. A. Enns, “Iron regulation by hepcidin Find the latest version : Science in medicine Iron regulation by hepcidin,” J. Clin. Invest., vol. 123, no. 6, pp. 2337–2343, 2013, doi: 10.1172/JCI67225.SMAD5.
16. T. Ganz, “Systemic iron homeostasis,” Physiol. Rev., vol. 93, no. 4, pp. 1721–1741, 2013, doi: 10.1152/physrev.00008.2013.
17. S. Canali, C. Vecchi, C. Garuti, G. Montosi, J. L. Babitt, and A. Pietrangelo, “The SMAD pathway is required for Hepcidin response during endoplasmic reticulum stress,” Endocrinology, vol. 157, no. 10, pp. 3935–3945, 2016, doi: 10.1210/en.2016-1258.
18. M. de la C. Ruiz-Jaramillo et al., “Iron overload as cardiovascular risk factor in children and adolescents with renal disease.,” Nephrol. Dial. Transplant, vol. 26, no. 10, pp. 3268–3273, 2011, doi: 10.1093/ndt/gfr044.
19. Y. Kanamori, M. Murakami, M. Sugiyama, O. Hashimoto, T. Matsui, and M. Funaba, “Interleukin-1β (IL-1β) transcriptionally activates hepcidin by inducing CCAAT enhancer-binding protein δ (C/EBPδ) expression in hepatocytes,” J. Biol. Chem., vol. 292, no. 24, pp. 10275–10287, 2017, doi: 10.1074/jbc.M116.770974.
20. D. W. Swinkels and J. F. M. Wetzels, “Hepcidin: A new tool in the management of anaemia in patients with chronic kidney disease?,” Nephrol. Dial. Transplant., vol. 23, no. 8, pp. 2450–2453, 2008, doi: 10.1093/ndt/gfn267.
21. M. A. Atkinson, J. Y. Kim, C. N. Roy, B. A. Warady, C. T. White, and S. L. Furth, “Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort,” Pediatr. Nephrol., vol. 30, no. 4, pp. 635–643, 2015, doi: 10.1007/s00467-014-2991-4.
22. N. R. Ridha and D. Daud, “Hubungan Kadar Hepcidin dengan Status Besi pada Inflamasi Akibat Obesitas,” Sari Pediatr., vol. 16, no. 3, p. 161, 2016, doi: 10.14238/sp16.3.2014.161-6.
23. T. Ganz and E. Nemeth, "Iron balance and the role of hepcidin in chronic kidney disease," Semin Nephrol. 2016 March; 36(2): 87 - 93. doi:10.1016/j.semnephrol.2016.02.001.
24. T. Eleftheriadis et al., “Ferroportin in monocytes of hemodialysis patients and its associations with hepcidin, inflammation, markers of iron status and resistance to erythropoietin,” Int. Urol. Nephrol., vol. 46, no. 1, pp. 161–167, 2014, doi: 10.1007/s11255-013-0497-9.