Clinical Utility of Reticulocyte Hemoglobin Equivalent (RET-He) and Related Indices in Predicting Erythropoietin Response in Hemodialysis Patients

  • Tejal Barot Assistant Professor, B. N. Patel Institute of Allied and Healthcare Sciences, Anand, Gujarat, India.
  • Dr. Ankita Bhatiya Associate Professor, L. P. Patel Institute of Allied Health Sciences and Technology, Karamsad, Gujarat, India.
  • Dr. Faruq Mulla Professor, Department of Pathology, Pramukhswami Medical College, Bhaikaka University, Karamsad, Gujarat, India.
Keywords: Erythropoietin Response, ESA Therapy, Hemodialysis, Iron Deficiency, RET-He, Reticulocyte Indices

Abstract

This study evaluated the predictive value of reticulocyte hemoglobin equivalent (RET-He) and related indices, including immature reticulocyte fraction (IRF) and mean reticulocyte volume (MRV), for assessing erythropoietin (EPO) responsiveness in 400 patients undergoing maintenance hemodialysis (HD). The objective was to determine whether RET-He could serve as a reliable biomarker of early erythropoietic activity and iron availability following EPO therapy.

Correlation, regression, and receiver operating characteristic (ROC) analyses were applied to explore relationships between baseline reticulocyte parameters and post-treatment hemoglobin response. RET-He exhibited a weak positive correlation (r = 0.0004, p = 0.993) with hemoglobin improvement, indicating negligible predictive capacity. Regression analysis revealed that baseline hemoglobin, not RET-He, independently predicted treatment response (p < 0.001). RET-He and IRF were useful for real-time diagnostic monitoring but not as prognostic indicators.

References

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. https://doi.org/10.3390/biomedicines12061191

Kim D, Lee J, Toyama T, Liyanage T, Woodward M, Matsushita K, et al. Prevalence and Treatment Patterns of Anaemia in Individuals With Chronic Kidney Disease Across Asia: A Systematic Review and Meta‐Analysis. Nephrology. 2025;30. https://doi.org/10.1111/nep.70002

Locatelli F, Aljama P, Bárány P, Canaud B, Carrera F, Eckardt KU, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant. 2004;19(Suppl 2):ii1–ii47. https://doi.org/10.1093/ndt/gfh1032

Matsuoka T, Abe M, Kobayashi H. Iron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction. Int J Mol Sci. 2024;25(7):3745. https://doi.org/10.3390/ijms25073745

Alageeli AA, Alqahtany FS, Algahtani FH. The Role of Reticulocyte Hemoglobin Content for the Diagnosis of Functional Iron Deficiency in Hemodialyzed patients. Saudi J Biol Sci. 2021;28(1):50–54. https://doi.org/10.1016/j.sjbs.2020.08.030

Almashjary MN, Barefah AS, Bahashwan S, Ashankyty I, ElFayoumi R, Alzahrani M, et al. Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity. J Clin Med. 2022;11(19):5675. https://doi.org/10.3390/jcm11195675

Hayes W. Measurement of iron status in chronic kidney disease. Pediatr Nephrol. 2018;34(4):605–613. https://doi.org/10.1007/s00467-018-3955-x

Peerschke EIB, Pessin MS, Maslak P. Using the Hemoglobin Content of Reticulocytes (RET-He) to Evaluate Anemia in Patients With Cancer. Am J Clin Pathol. 2014;142(4):506–512. https://doi.org/10.1309/ajcpcvz5b0boyjgn

Buttarello M, Pajola R, Novello E, Rebeschini M, Cantaro S, Oliosi F, et al. Diagnosis of Iron Deficiency in Patients Undergoing Hemodialysis. Am J Clin Pathol. 2010;133(6):949–954. https://doi.org/10.1309/ajcpqax0jfhfs0oa

Karunarathne P, Kulathilake C, Wijesiriwardena I, Hewageegana A, Marasinghe A. Evaluation of Iron Status by Reticulocyte Haemoglobin Content (Chr) in Chronic Kidney Disease Patients on Haemodialysis and Erythropoietin. Indian J Hematol Blood Transfus. 2021;38(2):359–365. https://doi.org/10.1007/s12288-021-01464-3

Lever J, Krzywinski M, Altman N. Principal component analysis. Nat Methods. 2017;14:641–642. https://doi.org/10.1038/nmeth.4346

Urrechaga E, Hoffmann JJ, Izquierdo S. Reticulocyte hemoglobin equivalent (RET-He) and assessment of iron-deficient states. Clin Chem Lab Med. 2016;54(7):1163–1169. https://doi.org/10.1515/cclm-2015-0818

Miwa N, Akiba T, Kimata N, Hamaguchi Y, Arakawa Y, Tamura T. Usefulness of reticulocyte hemoglobin equivalent in the management of hemodialysis patients. Clin Exp Nephrol. 2010;14(2):131–136. https://doi.org/10.1007/s10157-009-0261-2

Sany D, Elsharkawy A, El-Husseini A. Role of reticulocyte hemoglobin equivalent in assessment of iron deficiency in hemodialysis patients. Egypt J Intern Med. 2020;32:14. https://doi.org/10.1186/s43162-020-00014-z

Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. N Engl J Med. 2019;381(12):1148–1157. https://doi.org/10.1056/NEJMra1804281

Gangane NM, Anshu, et al. Evaluation of reticulocyte hemoglobin content in chronic kidney disease patients. J Clin Diagn Res. 2020;14(3):EC01–EC04. https://doi.org/10.7860/JCDR/2020/43469.13543

Published
2026-05-31
How to Cite
Barot, T., Bhatiya, D. A., & Mulla, D. F. (2026). Clinical Utility of Reticulocyte Hemoglobin Equivalent (RET-He) and Related Indices in Predicting Erythropoietin Response in Hemodialysis Patients. International Research in Medical and Health Sciences, 8(2), 20-25. Retrieved from https://www.irmhs.com/index.php/irmhs/article/view/243