Diagnostic Performance of Reticulocyte Hemoglobin Content ( CHr ) for Iron Deficiency in Chronic Kidney Disease: A Reanalysis of a Published South African Dataset

INTRODUCTION: Iron deficiency (ID) diagnosis in chronic kidney disease (CKD) is complicated by the limited reliability of ferritin as an acute-phase reactant. Reticulocyte hemoglobin content (CHr) provides a direct measure of iron available for erythropoiesis. We aimed to validate the diagnostic performance of CHr using a real-world dataset. METHODS: We performed a cross-sectional diagnostic accuracy analysis of the Nalado et al. dataset (n = 399; 258 CKD, 141 controls). CHr was measured on a Siemens ADVIA 2120 analyzer. ID was defined as absolute (AID; ferritin < 100 ng/mL and TSAT < 20%) or functional (FID; ferritin ≥ 100 ng/mL and TSAT < 20%). ROC analysis evaluated diagnostic performance. Multivariate logistic regression, adjusted for age, sex, and CKD status, assessed the independent predictive value of CHr. RESULTS: ID was present in 104 participants (26.1%). CHr was significantly lower in the ID group (28.0 ± 3.3 vs. 29.9 ± 2.7 pg; p < 0.0001). CHr yielded an AUC of 0.672 (95% CI: 0.610-0.731) with an optimal cut-off of 29.2 pg (sensitivity 64.4%, specificity 64.4%). In the CKD subgroup, performance improved (AUC = 0.738). CHr showed no correlation with ferritin (ρ = 0.010, p = 0.844). In multivariate analysis, CHr independently predicted ID (adjusted OR = 0.786; 95% CI: 0.709-0.872; p < 0.0001). CONCLUSION: CHr is a moderately useful, independent laboratory marker for iron-restricted erythropoiesis in CKD. Its lack of dependence on ferritin suggests value when standard biomarker interpretation is ambiguous. Prospective studies with concurrent inflammatory markers are warranted.