The Correlation between Reticulocyte Hemoglobin Equivalent (RET-He), Iron Status, and Erythrocyte Indices in Chronic Kidney Disease Patients at Prof. Dr. R.D. Kandou Manado Hospital
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Abstract
RET-He is a cost-effective parameter to assess iron status in CKD, but further research is necessary to assess its correlation with existing parameters. This study attempted to investigate the correlation between RET-He, iron status, and erythrocyte indices among CKD patients.
Materials and Methods: A cross-sectional study involving 110 CKD patients who underwent routine hematology and iron profile tests (serum iron/SI, total iron binding capacity/TIBC, transferrin saturation/TSAT, and ferritin). RET-He was then measured using a Sysmex XN-1000 hematology analyzer. Statistical tests were used to define the correlation between RET-He), iron status, and erythrocyte indices.
Results: There was a significant positive correlation between RET-He and SI (r = 0.349; p = 0.000), TSAT (r = 0.393; p = 0.000), and ferritin (r = 0.279; p = 0.003). Among CKD patients with excess iron levels, there was a moderate correlation between RET-He and TSAT (r = 0.404; p = 0.000).
Conclusion: The study found a significant correlation between RET-He levels and iron status markers in CKD patients. RET-He is recommended as an additional parameter to assess iron status and as an additional method to estimate TSAT and ferritin levels, especially in settings where chemistry analyzers are unavailable. Further research is required to establish RET-He cut-off values for identifying excessive iron levels in CKD patients.
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8. Vassalotti J, Centor R, Turner B, et al. Practical approach to detection and management of chronic kidney disease for the Primary Care Clinician. Am J Med. 2016;129 (2):153-162.e7.
9. Gaweda A. Markers of iron status in chronic kidney disease. Hemodial Int. 2017;21 Suppl 1(Suppl 1):S21-S27.
10. Thomas D, Hinchliffe R, Briggs C, et al. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161(5):639-648.
11. Van Wyck D, Alcorn H, Gupta R. Analytical and Biological Variation in Measures of Anemia and Iron Status in Patients Treated with Maintenance Hemodialysis. Am J Kidney Dis. 2010;56(3):540-6.
12. Chinudomwong P, Binyasing A, Trongsakul R, et al. Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status. J Clin Lab Anal. 2020; 34(6):e23225.
13. Dalimunthe N, Lubis A. Usefulness of Reticulocyte Hemoglobin Equivalent in Management of Regular Hemodialysis Patients with Iron Deficiency Anemia. Rom J Intern Med. 2016;54(1):31-6.
14. Davidkova S, Prestidge T, Reed P, et al. Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis. Pediatr Nephrol. 2016;31(5):819-26.
15. Rovani F, Nurulita A, Arif M. Analysis of Ret-He in Chronic Kidney Disease patients at DR.Wahidin Sudirohusodo Hospital, Makasar. Indones J Med Lab Technol. 2018;25(1):1-128.
16. Wirawan R, Tedja A, Henrika F, et al. Concordance between Reticulocyte Hemoglobin Equivalent and Reticulocyte Hemoglobin Content in CKD Patients Undergoing Hemodialysis. Acta Med Indones. 2017;49(1):34-40.
17. Abdul Gafor A, Subramaniam R, Hadi F, et al. The Role of Reticulocyte Hemoglobin Content in the Management of Iron Deficiency Anemia in Patients on Hemodialysis. Nephro Urol Mon. 2018;10(3): ; e65629.
18. Nakhoul G, Simon J. Anemia of chronic kidney disease: Treat it, but not too aggressively. Cleve Clin J Med. 2016;83(8):613-24.
19. Madiyono B, Moeslichan S, Sastroasmoro S, et al. Dasar-dasar metodologi penelitian klinis. Jakarta: 2011;348- 82.
20. Tumbelaka AR, Riono P, Sastroasmoro S, et al. Dasar-dasar metodologi penelitian klinis. Jakarta: 2011; 324-46.
21. Urrechaga E, Borque L, Escanero J. Potential utility of the new Sysmex XE 5000 red blood cell extended parameters in the study of disorders of iron metabolism. Clin Chem Lab Med. 2009;47(11):1411-6.
22. Joob B, Wiwanitkit V. Sysmex XE-5000 Analyser for Detecting Nucleated Red Blood Cells in Peripheral Blood. Clin Lab. 2014;60(12):2107.
23. Lukas DL, Hernaningsih Y, Triantanoe A. Diagnostic value of reticulocyte hemoglobin and soluble transferrin receptor in determining the iron status of chronics kidney disease with hemodialysis patients. Asian J Pharm Clin Res. 2019;12(9):210-14.
24. Hayes W. Measurement of iron status in chronic kidney disease. Pediatr Nephrol.2019;34(4):605-613.
25. Maconi M, Cavalca L, Danise P, et al. Erythrocyte and reticulocyte indices in iron deficiency in chronic kidney disease: comparison of two methods. Scand J Clin Lab Invest. 2009;69(3):365-70.
26. Harada A, Mitsuiki K, Miyata Y. Assessment of iron deficiency in chronic hemodialysis patients: investigation of cutoff values for reticulocyte hemoglobin content. Clin Exp Nephrol. 2003;7(1):52-7.
27. Venkatesan M, Saxena S, Kumar A. Evaluation of Iron Status in Patients of Chronic Kidney Disease - A study to assess the best Indicators Including Serum Transferrin Receptor Assay. Indian J Nephrol. 2019;29(4):248-253.
28. Chandrashekar K, Yashoda HT, Reddy VM. Utility of reticulocyte hemoglobin in diagnosing latent iron deficiency and iron deficiency anemia. Int J Contemp Pediatr. 2020;7(5):1049-1053.
29. Ahmed R, Fayek M, Salem D. Using Reticulocyte Hemoglobin Equivalent (RET- He) in Diagnosis of Iron Deficiency Anemia. QJM. 2020;113(Suppl.1):i59-i60.
30. Capone D, Cataldi M, Viniguerra M, et al. Reticulocyte Hemoglobin Content Helps Avoid Iron Overload in Hemodialysis Patients: A Retrospective Observational Study. In Vivo. 2017;31(4):709-12.
31. Aedh AI, Khalil MS, Abd-Elkader AS, et al. Reticulocyte hemoglobin as a screening test for iron deficiency anemia: A new cut-off. Hematol Rep. 2023;15(1):201–211.
32. Hönemann C, Hagemann O, Doll D, et al. [Reticulocyte hemoglobin equivalent as a diagnostic marker for the current iron deficiency: Old wine in new bottles]. Anaesthesist. 2020;69(12):919-925.
33. Torino AB, Gilberti M de, da Costa E, et al. Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease. Rev Bras Hematol Hemoter. 2015;37(2):77-81.
34. Kalantar-Zadeh K, Kleiner M, Dunne E, et al. Total iron-binding capacity–estimated transferrin correlates with the nutritional subjective global assessment in hemodialysis patients. Am J Kidney Dis. 1998;31(2):263-72.
35. Iron-binding capacity. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559119/.
36. Poventud‐Fuentes I, Chong TH, Dowlin M, et al. Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study. Int J Lab Hematol. 2024;46(1):148-155.
37. Neef V, Schmitt E, Bader P, et al. The reticulocyte hemoglobin equivalent as a screening marker for iron deficiency and iron deficiency anemia in children. J Clin Med. 2021;10(16):3506.
38. Dignass A, Farrag K, Stein J. Limitations of serum ferritin in diagnosing iron deficiency in inflammatory conditions. Int J Chronic Dis. 2018:2018:9394060.
2. Konsensus Manajemen Terapi Anemia Penyakit Ginjal Kronik. Perhimpunan Nefrologi Indonesia. 2011
3.11th Report of Indonesian Renal Registry [Internet]. Indonesianrenalregistry.org. 2018 [cited 29 June 2020]. Available from: https://www.indonesianrenalregistry.org/data/IRR%202018.pdf (unable to open)
4. Suwitra K. Penyakit ginjal kronik. In: Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata M, Setiasi S. Buku ajar ilmu penyakit dalam. Jakarta: 2010
5. Urrechaga E, Borque L, And FJ. Assessing Iron Status in CKD Patients: New Laboratory Parameters. Chronic Kidney Disease. 2012
6. Bailie G, Uhlig K, Levey A. Clinical Practice Guidelines in Nephrology: Evaluation, Classification, and Stratification of Chronic Kidney Disease. Pharmacotherapy. 2005;25(4):491-502.
7. Hoffbrand AV, Moss PAH. Eritropoesis dan aspek umum anemia. In: Kapita selekta Hematologi (Essensial Haematology) Edisi ke-6.2010: 13-28
8. Vassalotti J, Centor R, Turner B, et al. Practical approach to detection and management of chronic kidney disease for the Primary Care Clinician. Am J Med. 2016;129 (2):153-162.e7.
9. Gaweda A. Markers of iron status in chronic kidney disease. Hemodial Int. 2017;21 Suppl 1(Suppl 1):S21-S27.
10. Thomas D, Hinchliffe R, Briggs C, et al. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161(5):639-648.
11. Van Wyck D, Alcorn H, Gupta R. Analytical and Biological Variation in Measures of Anemia and Iron Status in Patients Treated with Maintenance Hemodialysis. Am J Kidney Dis. 2010;56(3):540-6.
12. Chinudomwong P, Binyasing A, Trongsakul R, et al. Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status. J Clin Lab Anal. 2020; 34(6):e23225.
13. Dalimunthe N, Lubis A. Usefulness of Reticulocyte Hemoglobin Equivalent in Management of Regular Hemodialysis Patients with Iron Deficiency Anemia. Rom J Intern Med. 2016;54(1):31-6.
14. Davidkova S, Prestidge T, Reed P, et al. Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis. Pediatr Nephrol. 2016;31(5):819-26.
15. Rovani F, Nurulita A, Arif M. Analysis of Ret-He in Chronic Kidney Disease patients at DR.Wahidin Sudirohusodo Hospital, Makasar. Indones J Med Lab Technol. 2018;25(1):1-128.
16. Wirawan R, Tedja A, Henrika F, et al. Concordance between Reticulocyte Hemoglobin Equivalent and Reticulocyte Hemoglobin Content in CKD Patients Undergoing Hemodialysis. Acta Med Indones. 2017;49(1):34-40.
17. Abdul Gafor A, Subramaniam R, Hadi F, et al. The Role of Reticulocyte Hemoglobin Content in the Management of Iron Deficiency Anemia in Patients on Hemodialysis. Nephro Urol Mon. 2018;10(3): ; e65629.
18. Nakhoul G, Simon J. Anemia of chronic kidney disease: Treat it, but not too aggressively. Cleve Clin J Med. 2016;83(8):613-24.
19. Madiyono B, Moeslichan S, Sastroasmoro S, et al. Dasar-dasar metodologi penelitian klinis. Jakarta: 2011;348- 82.
20. Tumbelaka AR, Riono P, Sastroasmoro S, et al. Dasar-dasar metodologi penelitian klinis. Jakarta: 2011; 324-46.
21. Urrechaga E, Borque L, Escanero J. Potential utility of the new Sysmex XE 5000 red blood cell extended parameters in the study of disorders of iron metabolism. Clin Chem Lab Med. 2009;47(11):1411-6.
22. Joob B, Wiwanitkit V. Sysmex XE-5000 Analyser for Detecting Nucleated Red Blood Cells in Peripheral Blood. Clin Lab. 2014;60(12):2107.
23. Lukas DL, Hernaningsih Y, Triantanoe A. Diagnostic value of reticulocyte hemoglobin and soluble transferrin receptor in determining the iron status of chronics kidney disease with hemodialysis patients. Asian J Pharm Clin Res. 2019;12(9):210-14.
24. Hayes W. Measurement of iron status in chronic kidney disease. Pediatr Nephrol.2019;34(4):605-613.
25. Maconi M, Cavalca L, Danise P, et al. Erythrocyte and reticulocyte indices in iron deficiency in chronic kidney disease: comparison of two methods. Scand J Clin Lab Invest. 2009;69(3):365-70.
26. Harada A, Mitsuiki K, Miyata Y. Assessment of iron deficiency in chronic hemodialysis patients: investigation of cutoff values for reticulocyte hemoglobin content. Clin Exp Nephrol. 2003;7(1):52-7.
27. Venkatesan M, Saxena S, Kumar A. Evaluation of Iron Status in Patients of Chronic Kidney Disease - A study to assess the best Indicators Including Serum Transferrin Receptor Assay. Indian J Nephrol. 2019;29(4):248-253.
28. Chandrashekar K, Yashoda HT, Reddy VM. Utility of reticulocyte hemoglobin in diagnosing latent iron deficiency and iron deficiency anemia. Int J Contemp Pediatr. 2020;7(5):1049-1053.
29. Ahmed R, Fayek M, Salem D. Using Reticulocyte Hemoglobin Equivalent (RET- He) in Diagnosis of Iron Deficiency Anemia. QJM. 2020;113(Suppl.1):i59-i60.
30. Capone D, Cataldi M, Viniguerra M, et al. Reticulocyte Hemoglobin Content Helps Avoid Iron Overload in Hemodialysis Patients: A Retrospective Observational Study. In Vivo. 2017;31(4):709-12.
31. Aedh AI, Khalil MS, Abd-Elkader AS, et al. Reticulocyte hemoglobin as a screening test for iron deficiency anemia: A new cut-off. Hematol Rep. 2023;15(1):201–211.
32. Hönemann C, Hagemann O, Doll D, et al. [Reticulocyte hemoglobin equivalent as a diagnostic marker for the current iron deficiency: Old wine in new bottles]. Anaesthesist. 2020;69(12):919-925.
33. Torino AB, Gilberti M de, da Costa E, et al. Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease. Rev Bras Hematol Hemoter. 2015;37(2):77-81.
34. Kalantar-Zadeh K, Kleiner M, Dunne E, et al. Total iron-binding capacity–estimated transferrin correlates with the nutritional subjective global assessment in hemodialysis patients. Am J Kidney Dis. 1998;31(2):263-72.
35. Iron-binding capacity. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559119/.
36. Poventud‐Fuentes I, Chong TH, Dowlin M, et al. Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study. Int J Lab Hematol. 2024;46(1):148-155.
37. Neef V, Schmitt E, Bader P, et al. The reticulocyte hemoglobin equivalent as a screening marker for iron deficiency and iron deficiency anemia in children. J Clin Med. 2021;10(16):3506.
38. Dignass A, Farrag K, Stein J. Limitations of serum ferritin in diagnosing iron deficiency in inflammatory conditions. Int J Chronic Dis. 2018:2018:9394060.
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| Issue | Vol 19 No 1 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v19i1.17824 | |
| Keywords | ||
| Reticulocyte hemoglobin equivalent; Iron status; Erythrocyte indices, CKD | ||
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How to Cite
1.
Raranta H, Adipireno P, Samsuria I. The Correlation between Reticulocyte Hemoglobin Equivalent (RET-He), Iron Status, and Erythrocyte Indices in Chronic Kidney Disease Patients at Prof. Dr. R.D. Kandou Manado Hospital. Int J Hematol Oncol Stem Cell Res. 2025;19(1):50-59.
