Comparative analysis of iron metabolism proteins in the pathogenesis of anemia in chronic kidney disease

Authors

DOI:

https://doi.org/10.14739/2310-1210.2026.3.338359

Keywords:

iron metabolism, erythropoietin, lactoferrin, hepcidin, chronic kidney disease

Abstract

Disturbances in iron metabolism play a key role in the pathophysiology of chronic kidney disease (CKD), contributing to clinical complications, particularly the development of anemia. Evaluating the diagnostic utility of iron metabolism proteins in CKD patients, depending on disease progression, is of great significance both diagnostically and therapeutically.

Aim: to evaluate the role of iron metabolism proteins in the pathogenesis of anemia and their clinical diagnostic value in patients with chronic kidney disease at both the conservative and terminal stages.

Materials and methods. The study included patients with stage II–III CKD (conservative group) and terminal-stage CKD undergoing hemodialysis (terminal group), as well as healthy controls. Serum levels of hemoglobin, iron, erythropoietin, ferritin, transferrin, lactoferrin, ferroportin, hepcidin, and haptoglobin were analyzed.

Results. In terminal-stage CKD, the concentrations of hemoglobin (22.1 %, p < 0.001 and 28.6 %, p = 0.001), erythropoietin (26.8 % and 32.5 %, p < 0.001), iron (18.3 %, p = 0.004 and 33.0 %, p < 0.001), TIBC (14.5 %, p < 0.001 and 17.3 %, p = 0.003), LIBC (14.4 %, p = 0.006 and 14.8 %, p = 0.039), and transferrin (11.3 %, p = 0.042 and 30.8 %, p = 0.008) were significantly lower in both men and women compared to the conservative group. In contrast, ferritin (2.3-fold and 2.1-fold, p < 0.001), hepcidin (82.2 % and 65.1 %, p < 0.001), ferroportin (50.0 % and 46.2 %, p < 0.001), and lactoferrin (2.2-fold and 87.5 %, p < 0.001) levels were significantly increased in the terminal stage group compared to the conservative group. Ferritin and hepcidin demonstrated the highest diagnostic performance in CKD, showing excellent sensitivity, specificity, and diagnostic efficiency. Lactoferrin and erythropoietin also showed strong diagnostic value, while ferroportin exhibited moderate diagnostic performance. Transferrin demonstrated the lowest diagnostic efficiency, indicating limited standalone clinical usefulness.

Conclusions. This study demonstrates that functional iron deficiency in end-stage renal disease is mediated by systemic inflammation. These findings underscore the pivotal role of iron metabolism proteins in the pathogenesis of renal anemia and validate their clinical utility as diagnostic biomarkers and therapeutic targets.

Author Biographies

G. M. Efendiyeva, Azerbaijan Medical University, Baku

MD, PhD student at the Department of Biochemistry

G. A. Jafarova, Azerbaijan Medical University, Baku

MD, Senior Researcher at the Department of Biochemistry

References

  1. Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022;12(1):7-11. doi: https://doi.org/10.1016/j.kisu.2021.11.003
    | |
  2. Vaidya SR, Aeddula NR. Chronic Kidney Disease. [Updated 2024 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535404/
  3. Badura K, Janc J, Wąsik J, Gnitecki S, Skwira S, Młynarska E, et al. Anemia of Chronic Kidney Disease-A Narrative Review of Its Pathophysiology, Diagnosis, and Management. Biomedicines. 2024;12(6):1191. doi: https://doi.org/10.3390/biomedicines12061191
    | |
  4. Hashmi MF, Shaikh H, Rout P. Anemia of Chronic Kidney Disease. [Updated 2024 Jul 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539871/
  5. Portolés J, Martín L, Broseta JJ, Cases A. Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents. Front Med (Lausanne). 2021;8:642296. doi: https://doi.org/10.3389/fmed.2021.642296
    | |
  6. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46(7):678-84. doi: https://doi.org/10.1038/ng.2996. Erratum in: Nat Genet. 2020;52(4):463. doi: https://doi.org/10.1038/s41588-019-0548-y
    | |
  7. Yiannikourides A, Latunde-Dada GO. A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders. Medicines (Basel). 2019;6(3):85. doi: https://doi.org/10.3390/medicines6030085
  8. Wang CY, Babitt JL. Hepcidin regulation in the anemia of inflammation. Curr Opin Hematol. 2016;23(3):189-97. doi: https://doi.org/10.1097/MOH.0000000000000236
    | |
  9. Nemeth E, Ganz T. Hepcidin and Iron in Health and Disease. Annu Rev Med. 2023;74:261-77. doi: https://doi.org/10.1146/annurev-med-043021-032816
    | |
  10. Fujisawa H, Nakayama M, Haruyama N, Fukui A, Yoshitomi R, Tsuruya K, et al. Association between iron status markers and kidney outcome in patients with chronic kidney disease. Sci Rep. 2023;13(1):18278. doi: https://doi.org/10.1038/s41598-023-45580-8
    | |
  11. Zapora-Kurel A, Malyszko J. Novel iron biomarkers in chronic kidney disease. Wiad Lek. 2021;74(12):3230-3. doi: https://doi.org/10.36740/wlek202112119
    | |
  12. Dignass A, Farrag K, Stein J. Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions. Int J Chronic Dis. 2018;2018:9394060. doi: https://doi.org/10.1155/2018/9394060
    |
  13. Zahan MS, Ahmed KA, Moni A, Sinopoli A, Ha H, Uddin MJ. Kidney protective potential of lactoferrin: pharmacological insights and therapeutic advances. Korean J Physiol Pharmacol. 2022;26(1):1-13. doi: https://doi.org/10.4196/kjpp.2022.26.1.1
    | |
  14. Rascón-Cruz Q, Siqueiros-Cendón TS, Siañez-Estrada LI, Villaseñor-Rivera CM, Ángel-Lerma LE, Olivas-Espino JA, et al. Antioxidant Potential of Lactoferrin and Its Protective Effect on Health: An Overview. Int J Mol Sci. 2024;26(1):125. doi: https://doi.org/10.3390/ijms26010125
    | |
  15. Yadav R, Sangha SS, Yadav S, Sharma P, Shah H, Bhowmik D. A Clinical Study to Evaluate the Anti-inflammatory Effect of Lactoferrin + Disodium Guanosine Monophosphate Therapy in the Patients with Chronic Kidney Disease. J Assoc Physicians India. 2025;73(1):18-22. doi: https://doi.org/10.59556/japi.73.0757
    | |
  16. Gulhar R, Ashraf MA, Jialal I. Physiology, Acute Phase Reactants. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519570/
  17. Terada K, Sumi Y, Aratani S, Hirama A, Kashiwagi T, Sakai Y. Plasma erythropoietin level and heart failure in patients undergoing peritoneal dialysis: a cross-sectional study. Ren Replace Ther. 2021;7:3. doi: https://doi.org/10.1186/s41100-021-00319-x
    |
  18. Yastremska OO, Lebed HB. [Iron metabolism in normal and pathological conditions]. Ukrainian Journal of Laboratory Medicine. 2023;1(2):45-51. Ukrainian. doi: https://doi.org/10.62151/2786-9288.1.2.2023.06
  19. McCullough K, Bolisetty S. Ferritins in Kidney Disease. Semin Nephrol. 2020;40(2):160-72. doi: https://doi.org/10.1016/j.semnephrol.2020.01.007
    | |
  20. Agarwal AK. Iron metabolism and management: focus on chronic kidney disease. Kidney Int Suppl (2011). 2021;11(1):46-58. doi: https://doi.org/10.1016/j.kisu.2020.12.003
    | |
  21. Ueda N, Takasawa K. Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease. Nutrients. 2018;10(9):1173. doi: https://doi.org/10.3390/nu10091173
    | |
  22. Matsuoka T, Abe M, Kobayashi H. Iron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction. Int J Mol Sci. 2024;25(7):3745. doi: https://doi.org/10.3390/ijms25073745
    | |
  23. Nemeth E, Ganz T. Hepcidin and iron-loading anemias. Haematologica. 2006;91(6):727-32.
    | |
  24. Ganz T. Hepcidin in iron metabolism. Curr Opin Hematol. 2004;11(4):251-4. doi: https://doi.org/10.1097/00062752-200407000-00004
    | |
  25. Hsu YH, Chiu IJ, Lin YF, Chen YJ, Lee YH, Chiu HW. Lactoferrin Contributes a Renoprotective Effect in Acute Kidney Injury and Early Renal Fibrosis. Pharmaceutics. 2020;12(5):434. doi: https://doi.org/10.3390/pharmaceutics12050434
    | |
  26. Fu J, Yang L, Tan D, Liu L. Iron transport mechanism of lactoferrin and its application in food processing. Food Sci Technol. 2023;43:e121122. doi: https://doi.org/10.1590/fst.121122
  27. Ganz T, Nemeth E. Iron Balance and the Role of Hepcidin in Chronic Kidney Disease. Semin Nephrol. 2016;36(2):87-93. doi: https://doi.org/10.1016/j.semnephrol.2016.02.001
    | |
  28. Jonny J, Sitepu EC, Azzalyka KA, Pasiak TF. Hepcidin in Hemodialysis Patients: An Update Review. Turkish J Nephrol. 2023;32(4):277-83. doi: https://doi.org/10.5152/turkjnephrol.2023.22422
    |
  29. Naoum FA. Adjusting thresholds of serum ferritin for iron deficiency: a moving target. Rev Bras Hematol Hemoter. 2017;39(3):189-90. doi: https://doi.org/10.1016/j.bjhh.2017.03.002
    | |
  30. Karlsson T. Evaluation of a competitive hepcidin ELISA assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients. J Inflamm (Lond). 2017;14:21. doi: https://doi.org/10.1186/s12950-017-0166-3
    | |

Downloads

Additional Files

Published

2026-06-11

How to Cite

1.
Efendiyeva GM, Jafarova GA. Comparative analysis of iron metabolism proteins in the pathogenesis of anemia in chronic kidney disease. Zaporozhye Medical Journal [Internet]. 2026Jun.11 [cited 2026Jun.11];28(3):217-24. Available from: https://zmj.zsmu.edu.ua/article/view/338359

Issue

Vol. 28 No. 3 (2026): Zaporozhye Medical Journal

Section

Original research

License

Copyright (c) 2025 G. M. Efendiyeva, G. A. Jafarova

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.  Лицензия Creative Commons