Clinical Utility, Sensitivity, and Specificity of Reticulocyte Hemoglobin Content for Diagnosing Iron Deficiency Anemia in Hemodialysis Patients: A Systematic Review and Meta-Analysis

Sae'd M Abu El-Kass^1*Marwa Mostafa Ragheb²Hadiya Nassar Alrashedi³Maha Alotaibi³Faisal Masnad Alrashidi⁴

• ¹University College of Applied Sciences, Gaza City, Palestine
• ²Medical Surgical Nursing, Faculty of Nursing, Benha University, Egypt., Banha, Egypt
• ³Qassim Health cluster, Buraidah, Kingdom Saudi Arabia, Buraidah, Saudi Arabia
• ⁴Ministry of Health, Kingdom Saudi Arabia, Qassim, Al-Qassim, Saudi Arabia

Background: Early detection of iron deficiency anemia (IDA) in patients undergoing hemodialysis is crucial to avoid the harmful long-term effects associated with the condition. This meta-analysis aims to assess the clinical value, diagnostic sensitivity, and specificity of reticulocyte hemoglobin content (CHr) as a biomarker for identifying IDA in individuals receiving hemodialysis treatment. Methods: A PRISMA-guided systematic review and meta-analysis were performed. Comprehensive searches were carried out across six major databases Web of Science, PubMed, ScienceDirect, Embase, MEDLINE, and Google Scholar, up to November 16, 2024, to locate all relevant English-language studies. Data were extracted from eligible publications, and a random-effects model was applied for the meta-analysis. Subgroup analyses were conducted to evaluate the diagnostic sensitivity and specificity of CHr for identifying IDA in hemodialysis patients. Study heterogeneity was examined using Cochran’s Q and the I² statistic. The review protocol was registered with PROSPERO under the ID CRD42023440120. Results: The initial search identified 14,457 articles, from which 22 studies were included, comprising 2,289 hemodialysis patients. The mean CHr cut-off value for diagnosing IDA was 30.3 pg. The pooled sensitivity of CHr was 84.3% (95% CI: 77.4% to 89.3%) and the specificity was 77.7% (95% CI: 72.0% to 82.6%). Substantial heterogeneity was observed in both sensitivity (I² = 89%) and specificity (I² = 81%). Conclusion: This systematic review and meta-analysis indicate that CHr demonstrates generally high sensitivity and specificity for diagnosing IDA in hemodialysis patients, supporting its potential as a useful clinical biomarker. However, considerable heterogeneity among studies highlights the need for further standardized research before CHr can be universally recommended as a standalone diagnostic tool. Clinicians should interpret CHr results alongside other clinical and laboratory findings to guide anemia management effectively.